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Fatty liver in ChinaFatty liver in China ----a common and weighty problema common and weighty problem----
JianJian--GaoGao FanFan MD PhDMD PhD
Department of GastroenterologyDepartment of GastroenterologyXinhua Hospital Xinhua Hospital
JiaotongJiaotong University School of Medicine University School of Medicine Shanghai 200092 ChinaShanghai 200092 China
httphttpwwwcwwwchzfgcomhzfgcom
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Fatty liver in given specific Chinese populationFatty liver in given specific Chinese population
Labor workers in Labor workers in DaqingDaqing LiaoninLiaonin (n=4100)(n=4100) 5 5
Labor workers in Beijing Labor workers in Beijing (n=1050)(n=1050) 11 11
Employees in Employees in ShaoxingShaoxing Zhejiang Zhejiang (n=11372)(n=11372) 10 10
White collars in Beijing White collars in Beijing (n=818)(n=818) 18 18
White collars in Shanghai White collars in Shanghai (n=4009)(n=4009) 13 13
Among 6553 employees in Lianyungang Jiangsu Among 6553 employees in Lianyungang Jiangsu retired cadre 10 policemen 9 clerk 6 retired cadre 10 policemen 9 clerk 6 workmen 4workmen 4
Fan JG Fan JG ShijieShijie HuarenHuaren XiaohuaXiaohua ZazhiZazhi 200196200196--1010
Epidemiological studies in FLDEpidemiological studies in FLD
Case definitionCase definition
Liver biopsyLiver biopsy
CT scanCT scan
UltrasoundUltrasound
ALTASTGGTALTASTGGT
Sampling frameSampling frame
PopulationPopulation
CommunityCommunity
Clinical basedClinical based
Hospital basedHospital based
----ConsecutiveNonConsecutiveNon--consecutiveconsecutive
Ultrasound of fatty liverUltrasound of fatty liver
Fatty liver in general population in ChinaFatty liver in general population in China
CityYearCityYear PrevalencePrevalence EtiologyEtiology Others Others Shanghai2005Shanghai2005 173173 NAFL 15 NAFL 15
AFL 08AFL 08Other 12Other 12
Drinking 13Drinking 13
Guangzhou2007Guangzhou2007 145145 NAFL 117NAFL 117AFL 05AFL 05Other 18Other 18
Children 13Children 13
XiXirsquorsquoan2008an2008 136136 NAFL 147NAFL 147AFL 87AFL 87
Drinking 66Drinking 66
Chengdu2009Chengdu2009 125125 NAFL 63 NAFL 63 AFL 26AFL 26Other 36Other 36
Beijing2013Beijing2013 351351 NAFL 313NAFL 313AFL 41AFL 41
Fan J Hepatol 2005 43508-14 Zhou WJG 2007136419-24 Yan Hepatol Int 2008 2S86-S87 Li HBPD Int 20098377-82Yan JGH 2013 281654-9
Prevalence of Fatty Liver in Shanghai Adults Prevalence of Fatty Liver in Shanghai Adults
Total 17Total 17
Male 19 Male 19
Female 15Female 15
NAFLD 15NAFLD 15
AFL 08AFL 08
Mixed FL 12Mixed FL 12
Fan JG et al J Hepatol 2005 43508ndash514
5 7
NAFLD 88
AFLMixed FL
Increased prevalence of fatty liver in ChinaIncreased prevalence of fatty liver in China
CityCity PeriodPeriod SubjectsSubjects Trend Trend BeijingBeijing 19981998--20032003 Administrative Administrative
officersofficers23 to 2623 to 26
ShanghaiShanghai 19951995--20022002 Factory Factory workersworkers
4 to 144 to 14
WuhanWuhan 19951995--20042004 Office workersOffice workers 125 to 125 to 245245
Fan JG JGH 200722663-8 Wang Z Postgrad Med J 200783192-5 unpublished
Increased prevalence of FL in Shanghai factory Increased prevalence of FL in Shanghai factory
workers between 1995 and 2002workers between 1995 and 2002
0
10
20
30
40
50
60
1995- 1997- 1999- 2001-
Fatty liver
Habitualdrinking
FLAbnormalALT
Obesity
Daibetes
Hypertension
Hyper-TG
Hyper-TC
Fan JG et al J Gastroenterol Hepatol 200722663-68
Incidence of NAFLD in ShanghaiIncidence of NAFLD in Shanghai
5226 non5226 non--drinking workers without USdrinking workers without US--fatty liver at fatty liver at baseline baseline
After 2After 2--year followyear follow--up 310 pts up 310 pts (62) were found to (62) were found to have NAFLD have NAFLD
Incidence of NAFLD Incidence of NAFLD (3 new cases100 people year)(3 new cases100 people year) is equal to is equal to that in that in DionysosDionysos studystudy
The baseline BMI serum triglyceride and their subtle The baseline BMI serum triglyceride and their subtle gain during followgain during follow--up were independent predictors of up were independent predictors of incident of NAFLD incident of NAFLD
Fan et al Hepatol International 2010
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
0
10
20
30
40
16-19 20-29 30-39 40-49 50-59 60-69 70 up
Age
AllMaleFemale
Prevalence of NAFLD increases with age (plt00001) peak 60-69 yrPrevalence of NALFD increases with age in male (p=000011) and female (plt00001)Peak prevalence male 40-49 female 60-69 yr
Fan JG et al J Hepatol 2005
Age- amp sex- related prevalence of fatty liver in Shanghai
Risk factor for fatty liverRisk factor for fatty liver disease disease among Shanghai administrative officersamong Shanghai administrative officers
Risk factorsRisk factors
CCentral obesityentral obesity
ObesityObesity
DyslipidemiaDyslipidemia
DiabetesDiabetes
HypertensionHypertension
Heavy alcohol drinkingHeavy alcohol drinking
Eat or sleep too muchEat or sleep too much
High fat dietHigh fat diet
Physical inactivityPhysical inactivity
Protective factorsProtective factors
ExerciseExercise
Mild alcohol drinkingMild alcohol drinking
Work in moderate stressWork in moderate stress
Fan JG et al Chin J Prev Med 1997 JGH 2013
Criteria for obesity and Criteria for obesity and MetSMetS ethnic differencesethnic differences
Only 2Only 2--3 of Asians 3 of Asians classified as obesity by classified as obesity by Western criteria Western criteria
Compared to Caucasians Compared to Caucasians with same BMI Asian with same BMI Asian people has more visceral people has more visceral fat and less lean body fat and less lean body massmass
Regional criteria of Regional criteria of obesitycentral obesity obesitycentral obesity and and MetSMetS are used in most are used in most Asian studiesAsian studies
IDF Central obesity by waist circumferenceIDF Central obesity by waist circumference
Ethnic groupEthnic group MaleMale FemaleFemale
EuropridsEuroprids 94 cm94 cm 80 cm80 cm
US likelyUS likely 102 cm102 cm 88 cm88 cm
Lancet 2005 3661059
Ethnic groupEthnic group MaleMale FemaleFemale
South Asians South Asians ChineseChinese
90 cm90 cm 80 cm80 cm
JapaneseJapanese 85 cm85 cm 90 cm90 cm
MetSMetS Features in Groups with amp without FLFeatures in Groups with amp without FL
OverweightOverweightObesityObesity
522522 (7897)(7897) 809809 (3218)(3218) 562887562887 lt 00001lt 00001
AbdAbd obesityobesity 474474 (7171)(7171) 662662 (2633)(2633) 468867468867 lt 00001lt 00001
Impaired FGImpaired FG 8181 (1225)(1225) 190190 (756)(756) 1478314783 lt 0001lt 0001
Impaired GTImpaired GT 2525 (378)(378) 2525 (099)(099) 2623326233 lt 00001lt 00001
D MD M 215215 (3253)(3253) 297297 (1181)(1181) 165960165960 lt 00001lt 00001
DyslipidemiaDyslipidemia 467467 (5719)(5719) 999999 (3974)(3974) 4875148751 lt 00001lt 00001
HypertensionHypertension 464464 (7020)(7020) 10711071 (4260)(4260) 159547159547 lt 00001lt 00001
Features Fatty liver n=661 ()
No fatty liver n=2514 ()
T-value p-value
Fan JG et al JGH 2005 201825-32
Less than high Less than high school school educationeducation
306306 (4629)(4629) 825825 (3282)(3282) 4144141441 lt0001lt0001
PovertyPoverty--toto--income income ratiolt1ratiolt1
4949 (741)(741) 245245 (975)(975) 33883388 0065700657
Physical inactivityPhysical inactivity 471471 (7126)(7126) 14721472 (5855)(5855) 3555835558 lt00001lt00001
Current cigarette Current cigarette smokingsmoking
8787 (1316)(1316) 276276 (1098)(1098) 24632463 0116501165
Current habitual Current habitual drinkingdrinking
6161 (923)(923) 181181 (720)(720) 30583058 0080300803
Other Features in Groups with amp without Fatty LiverOther Features in Groups with amp without Fatty LiverFeatures With fatty liver
n=661 ()No fatty liver n=2514 ()
T-value p-value
Fan JG et al J Hepatol 2005 43508-14
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Fatty liver in given specific Chinese populationFatty liver in given specific Chinese population
Labor workers in Labor workers in DaqingDaqing LiaoninLiaonin (n=4100)(n=4100) 5 5
Labor workers in Beijing Labor workers in Beijing (n=1050)(n=1050) 11 11
Employees in Employees in ShaoxingShaoxing Zhejiang Zhejiang (n=11372)(n=11372) 10 10
White collars in Beijing White collars in Beijing (n=818)(n=818) 18 18
White collars in Shanghai White collars in Shanghai (n=4009)(n=4009) 13 13
Among 6553 employees in Lianyungang Jiangsu Among 6553 employees in Lianyungang Jiangsu retired cadre 10 policemen 9 clerk 6 retired cadre 10 policemen 9 clerk 6 workmen 4workmen 4
Fan JG Fan JG ShijieShijie HuarenHuaren XiaohuaXiaohua ZazhiZazhi 200196200196--1010
Epidemiological studies in FLDEpidemiological studies in FLD
Case definitionCase definition
Liver biopsyLiver biopsy
CT scanCT scan
UltrasoundUltrasound
ALTASTGGTALTASTGGT
Sampling frameSampling frame
PopulationPopulation
CommunityCommunity
Clinical basedClinical based
Hospital basedHospital based
----ConsecutiveNonConsecutiveNon--consecutiveconsecutive
Ultrasound of fatty liverUltrasound of fatty liver
Fatty liver in general population in ChinaFatty liver in general population in China
CityYearCityYear PrevalencePrevalence EtiologyEtiology Others Others Shanghai2005Shanghai2005 173173 NAFL 15 NAFL 15
AFL 08AFL 08Other 12Other 12
Drinking 13Drinking 13
Guangzhou2007Guangzhou2007 145145 NAFL 117NAFL 117AFL 05AFL 05Other 18Other 18
Children 13Children 13
XiXirsquorsquoan2008an2008 136136 NAFL 147NAFL 147AFL 87AFL 87
Drinking 66Drinking 66
Chengdu2009Chengdu2009 125125 NAFL 63 NAFL 63 AFL 26AFL 26Other 36Other 36
Beijing2013Beijing2013 351351 NAFL 313NAFL 313AFL 41AFL 41
Fan J Hepatol 2005 43508-14 Zhou WJG 2007136419-24 Yan Hepatol Int 2008 2S86-S87 Li HBPD Int 20098377-82Yan JGH 2013 281654-9
Prevalence of Fatty Liver in Shanghai Adults Prevalence of Fatty Liver in Shanghai Adults
Total 17Total 17
Male 19 Male 19
Female 15Female 15
NAFLD 15NAFLD 15
AFL 08AFL 08
Mixed FL 12Mixed FL 12
Fan JG et al J Hepatol 2005 43508ndash514
5 7
NAFLD 88
AFLMixed FL
Increased prevalence of fatty liver in ChinaIncreased prevalence of fatty liver in China
CityCity PeriodPeriod SubjectsSubjects Trend Trend BeijingBeijing 19981998--20032003 Administrative Administrative
officersofficers23 to 2623 to 26
ShanghaiShanghai 19951995--20022002 Factory Factory workersworkers
4 to 144 to 14
WuhanWuhan 19951995--20042004 Office workersOffice workers 125 to 125 to 245245
Fan JG JGH 200722663-8 Wang Z Postgrad Med J 200783192-5 unpublished
Increased prevalence of FL in Shanghai factory Increased prevalence of FL in Shanghai factory
workers between 1995 and 2002workers between 1995 and 2002
0
10
20
30
40
50
60
1995- 1997- 1999- 2001-
Fatty liver
Habitualdrinking
FLAbnormalALT
Obesity
Daibetes
Hypertension
Hyper-TG
Hyper-TC
Fan JG et al J Gastroenterol Hepatol 200722663-68
Incidence of NAFLD in ShanghaiIncidence of NAFLD in Shanghai
5226 non5226 non--drinking workers without USdrinking workers without US--fatty liver at fatty liver at baseline baseline
After 2After 2--year followyear follow--up 310 pts up 310 pts (62) were found to (62) were found to have NAFLD have NAFLD
Incidence of NAFLD Incidence of NAFLD (3 new cases100 people year)(3 new cases100 people year) is equal to is equal to that in that in DionysosDionysos studystudy
The baseline BMI serum triglyceride and their subtle The baseline BMI serum triglyceride and their subtle gain during followgain during follow--up were independent predictors of up were independent predictors of incident of NAFLD incident of NAFLD
Fan et al Hepatol International 2010
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
0
10
20
30
40
16-19 20-29 30-39 40-49 50-59 60-69 70 up
Age
AllMaleFemale
Prevalence of NAFLD increases with age (plt00001) peak 60-69 yrPrevalence of NALFD increases with age in male (p=000011) and female (plt00001)Peak prevalence male 40-49 female 60-69 yr
Fan JG et al J Hepatol 2005
Age- amp sex- related prevalence of fatty liver in Shanghai
Risk factor for fatty liverRisk factor for fatty liver disease disease among Shanghai administrative officersamong Shanghai administrative officers
Risk factorsRisk factors
CCentral obesityentral obesity
ObesityObesity
DyslipidemiaDyslipidemia
DiabetesDiabetes
HypertensionHypertension
Heavy alcohol drinkingHeavy alcohol drinking
Eat or sleep too muchEat or sleep too much
High fat dietHigh fat diet
Physical inactivityPhysical inactivity
Protective factorsProtective factors
ExerciseExercise
Mild alcohol drinkingMild alcohol drinking
Work in moderate stressWork in moderate stress
Fan JG et al Chin J Prev Med 1997 JGH 2013
Criteria for obesity and Criteria for obesity and MetSMetS ethnic differencesethnic differences
Only 2Only 2--3 of Asians 3 of Asians classified as obesity by classified as obesity by Western criteria Western criteria
Compared to Caucasians Compared to Caucasians with same BMI Asian with same BMI Asian people has more visceral people has more visceral fat and less lean body fat and less lean body massmass
Regional criteria of Regional criteria of obesitycentral obesity obesitycentral obesity and and MetSMetS are used in most are used in most Asian studiesAsian studies
IDF Central obesity by waist circumferenceIDF Central obesity by waist circumference
Ethnic groupEthnic group MaleMale FemaleFemale
EuropridsEuroprids 94 cm94 cm 80 cm80 cm
US likelyUS likely 102 cm102 cm 88 cm88 cm
Lancet 2005 3661059
Ethnic groupEthnic group MaleMale FemaleFemale
South Asians South Asians ChineseChinese
90 cm90 cm 80 cm80 cm
JapaneseJapanese 85 cm85 cm 90 cm90 cm
MetSMetS Features in Groups with amp without FLFeatures in Groups with amp without FL
OverweightOverweightObesityObesity
522522 (7897)(7897) 809809 (3218)(3218) 562887562887 lt 00001lt 00001
AbdAbd obesityobesity 474474 (7171)(7171) 662662 (2633)(2633) 468867468867 lt 00001lt 00001
Impaired FGImpaired FG 8181 (1225)(1225) 190190 (756)(756) 1478314783 lt 0001lt 0001
Impaired GTImpaired GT 2525 (378)(378) 2525 (099)(099) 2623326233 lt 00001lt 00001
D MD M 215215 (3253)(3253) 297297 (1181)(1181) 165960165960 lt 00001lt 00001
DyslipidemiaDyslipidemia 467467 (5719)(5719) 999999 (3974)(3974) 4875148751 lt 00001lt 00001
HypertensionHypertension 464464 (7020)(7020) 10711071 (4260)(4260) 159547159547 lt 00001lt 00001
Features Fatty liver n=661 ()
No fatty liver n=2514 ()
T-value p-value
Fan JG et al JGH 2005 201825-32
Less than high Less than high school school educationeducation
306306 (4629)(4629) 825825 (3282)(3282) 4144141441 lt0001lt0001
PovertyPoverty--toto--income income ratiolt1ratiolt1
4949 (741)(741) 245245 (975)(975) 33883388 0065700657
Physical inactivityPhysical inactivity 471471 (7126)(7126) 14721472 (5855)(5855) 3555835558 lt00001lt00001
Current cigarette Current cigarette smokingsmoking
8787 (1316)(1316) 276276 (1098)(1098) 24632463 0116501165
Current habitual Current habitual drinkingdrinking
6161 (923)(923) 181181 (720)(720) 30583058 0080300803
Other Features in Groups with amp without Fatty LiverOther Features in Groups with amp without Fatty LiverFeatures With fatty liver
n=661 ()No fatty liver n=2514 ()
T-value p-value
Fan JG et al J Hepatol 2005 43508-14
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Fatty liver in given specific Chinese populationFatty liver in given specific Chinese population
Labor workers in Labor workers in DaqingDaqing LiaoninLiaonin (n=4100)(n=4100) 5 5
Labor workers in Beijing Labor workers in Beijing (n=1050)(n=1050) 11 11
Employees in Employees in ShaoxingShaoxing Zhejiang Zhejiang (n=11372)(n=11372) 10 10
White collars in Beijing White collars in Beijing (n=818)(n=818) 18 18
White collars in Shanghai White collars in Shanghai (n=4009)(n=4009) 13 13
Among 6553 employees in Lianyungang Jiangsu Among 6553 employees in Lianyungang Jiangsu retired cadre 10 policemen 9 clerk 6 retired cadre 10 policemen 9 clerk 6 workmen 4workmen 4
Fan JG Fan JG ShijieShijie HuarenHuaren XiaohuaXiaohua ZazhiZazhi 200196200196--1010
Epidemiological studies in FLDEpidemiological studies in FLD
Case definitionCase definition
Liver biopsyLiver biopsy
CT scanCT scan
UltrasoundUltrasound
ALTASTGGTALTASTGGT
Sampling frameSampling frame
PopulationPopulation
CommunityCommunity
Clinical basedClinical based
Hospital basedHospital based
----ConsecutiveNonConsecutiveNon--consecutiveconsecutive
Ultrasound of fatty liverUltrasound of fatty liver
Fatty liver in general population in ChinaFatty liver in general population in China
CityYearCityYear PrevalencePrevalence EtiologyEtiology Others Others Shanghai2005Shanghai2005 173173 NAFL 15 NAFL 15
AFL 08AFL 08Other 12Other 12
Drinking 13Drinking 13
Guangzhou2007Guangzhou2007 145145 NAFL 117NAFL 117AFL 05AFL 05Other 18Other 18
Children 13Children 13
XiXirsquorsquoan2008an2008 136136 NAFL 147NAFL 147AFL 87AFL 87
Drinking 66Drinking 66
Chengdu2009Chengdu2009 125125 NAFL 63 NAFL 63 AFL 26AFL 26Other 36Other 36
Beijing2013Beijing2013 351351 NAFL 313NAFL 313AFL 41AFL 41
Fan J Hepatol 2005 43508-14 Zhou WJG 2007136419-24 Yan Hepatol Int 2008 2S86-S87 Li HBPD Int 20098377-82Yan JGH 2013 281654-9
Prevalence of Fatty Liver in Shanghai Adults Prevalence of Fatty Liver in Shanghai Adults
Total 17Total 17
Male 19 Male 19
Female 15Female 15
NAFLD 15NAFLD 15
AFL 08AFL 08
Mixed FL 12Mixed FL 12
Fan JG et al J Hepatol 2005 43508ndash514
5 7
NAFLD 88
AFLMixed FL
Increased prevalence of fatty liver in ChinaIncreased prevalence of fatty liver in China
CityCity PeriodPeriod SubjectsSubjects Trend Trend BeijingBeijing 19981998--20032003 Administrative Administrative
officersofficers23 to 2623 to 26
ShanghaiShanghai 19951995--20022002 Factory Factory workersworkers
4 to 144 to 14
WuhanWuhan 19951995--20042004 Office workersOffice workers 125 to 125 to 245245
Fan JG JGH 200722663-8 Wang Z Postgrad Med J 200783192-5 unpublished
Increased prevalence of FL in Shanghai factory Increased prevalence of FL in Shanghai factory
workers between 1995 and 2002workers between 1995 and 2002
0
10
20
30
40
50
60
1995- 1997- 1999- 2001-
Fatty liver
Habitualdrinking
FLAbnormalALT
Obesity
Daibetes
Hypertension
Hyper-TG
Hyper-TC
Fan JG et al J Gastroenterol Hepatol 200722663-68
Incidence of NAFLD in ShanghaiIncidence of NAFLD in Shanghai
5226 non5226 non--drinking workers without USdrinking workers without US--fatty liver at fatty liver at baseline baseline
After 2After 2--year followyear follow--up 310 pts up 310 pts (62) were found to (62) were found to have NAFLD have NAFLD
Incidence of NAFLD Incidence of NAFLD (3 new cases100 people year)(3 new cases100 people year) is equal to is equal to that in that in DionysosDionysos studystudy
The baseline BMI serum triglyceride and their subtle The baseline BMI serum triglyceride and their subtle gain during followgain during follow--up were independent predictors of up were independent predictors of incident of NAFLD incident of NAFLD
Fan et al Hepatol International 2010
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
0
10
20
30
40
16-19 20-29 30-39 40-49 50-59 60-69 70 up
Age
AllMaleFemale
Prevalence of NAFLD increases with age (plt00001) peak 60-69 yrPrevalence of NALFD increases with age in male (p=000011) and female (plt00001)Peak prevalence male 40-49 female 60-69 yr
Fan JG et al J Hepatol 2005
Age- amp sex- related prevalence of fatty liver in Shanghai
Risk factor for fatty liverRisk factor for fatty liver disease disease among Shanghai administrative officersamong Shanghai administrative officers
Risk factorsRisk factors
CCentral obesityentral obesity
ObesityObesity
DyslipidemiaDyslipidemia
DiabetesDiabetes
HypertensionHypertension
Heavy alcohol drinkingHeavy alcohol drinking
Eat or sleep too muchEat or sleep too much
High fat dietHigh fat diet
Physical inactivityPhysical inactivity
Protective factorsProtective factors
ExerciseExercise
Mild alcohol drinkingMild alcohol drinking
Work in moderate stressWork in moderate stress
Fan JG et al Chin J Prev Med 1997 JGH 2013
Criteria for obesity and Criteria for obesity and MetSMetS ethnic differencesethnic differences
Only 2Only 2--3 of Asians 3 of Asians classified as obesity by classified as obesity by Western criteria Western criteria
Compared to Caucasians Compared to Caucasians with same BMI Asian with same BMI Asian people has more visceral people has more visceral fat and less lean body fat and less lean body massmass
Regional criteria of Regional criteria of obesitycentral obesity obesitycentral obesity and and MetSMetS are used in most are used in most Asian studiesAsian studies
IDF Central obesity by waist circumferenceIDF Central obesity by waist circumference
Ethnic groupEthnic group MaleMale FemaleFemale
EuropridsEuroprids 94 cm94 cm 80 cm80 cm
US likelyUS likely 102 cm102 cm 88 cm88 cm
Lancet 2005 3661059
Ethnic groupEthnic group MaleMale FemaleFemale
South Asians South Asians ChineseChinese
90 cm90 cm 80 cm80 cm
JapaneseJapanese 85 cm85 cm 90 cm90 cm
MetSMetS Features in Groups with amp without FLFeatures in Groups with amp without FL
OverweightOverweightObesityObesity
522522 (7897)(7897) 809809 (3218)(3218) 562887562887 lt 00001lt 00001
AbdAbd obesityobesity 474474 (7171)(7171) 662662 (2633)(2633) 468867468867 lt 00001lt 00001
Impaired FGImpaired FG 8181 (1225)(1225) 190190 (756)(756) 1478314783 lt 0001lt 0001
Impaired GTImpaired GT 2525 (378)(378) 2525 (099)(099) 2623326233 lt 00001lt 00001
D MD M 215215 (3253)(3253) 297297 (1181)(1181) 165960165960 lt 00001lt 00001
DyslipidemiaDyslipidemia 467467 (5719)(5719) 999999 (3974)(3974) 4875148751 lt 00001lt 00001
HypertensionHypertension 464464 (7020)(7020) 10711071 (4260)(4260) 159547159547 lt 00001lt 00001
Features Fatty liver n=661 ()
No fatty liver n=2514 ()
T-value p-value
Fan JG et al JGH 2005 201825-32
Less than high Less than high school school educationeducation
306306 (4629)(4629) 825825 (3282)(3282) 4144141441 lt0001lt0001
PovertyPoverty--toto--income income ratiolt1ratiolt1
4949 (741)(741) 245245 (975)(975) 33883388 0065700657
Physical inactivityPhysical inactivity 471471 (7126)(7126) 14721472 (5855)(5855) 3555835558 lt00001lt00001
Current cigarette Current cigarette smokingsmoking
8787 (1316)(1316) 276276 (1098)(1098) 24632463 0116501165
Current habitual Current habitual drinkingdrinking
6161 (923)(923) 181181 (720)(720) 30583058 0080300803
Other Features in Groups with amp without Fatty LiverOther Features in Groups with amp without Fatty LiverFeatures With fatty liver
n=661 ()No fatty liver n=2514 ()
T-value p-value
Fan JG et al J Hepatol 2005 43508-14
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Epidemiological studies in FLDEpidemiological studies in FLD
Case definitionCase definition
Liver biopsyLiver biopsy
CT scanCT scan
UltrasoundUltrasound
ALTASTGGTALTASTGGT
Sampling frameSampling frame
PopulationPopulation
CommunityCommunity
Clinical basedClinical based
Hospital basedHospital based
----ConsecutiveNonConsecutiveNon--consecutiveconsecutive
Ultrasound of fatty liverUltrasound of fatty liver
Fatty liver in general population in ChinaFatty liver in general population in China
CityYearCityYear PrevalencePrevalence EtiologyEtiology Others Others Shanghai2005Shanghai2005 173173 NAFL 15 NAFL 15
AFL 08AFL 08Other 12Other 12
Drinking 13Drinking 13
Guangzhou2007Guangzhou2007 145145 NAFL 117NAFL 117AFL 05AFL 05Other 18Other 18
Children 13Children 13
XiXirsquorsquoan2008an2008 136136 NAFL 147NAFL 147AFL 87AFL 87
Drinking 66Drinking 66
Chengdu2009Chengdu2009 125125 NAFL 63 NAFL 63 AFL 26AFL 26Other 36Other 36
Beijing2013Beijing2013 351351 NAFL 313NAFL 313AFL 41AFL 41
Fan J Hepatol 2005 43508-14 Zhou WJG 2007136419-24 Yan Hepatol Int 2008 2S86-S87 Li HBPD Int 20098377-82Yan JGH 2013 281654-9
Prevalence of Fatty Liver in Shanghai Adults Prevalence of Fatty Liver in Shanghai Adults
Total 17Total 17
Male 19 Male 19
Female 15Female 15
NAFLD 15NAFLD 15
AFL 08AFL 08
Mixed FL 12Mixed FL 12
Fan JG et al J Hepatol 2005 43508ndash514
5 7
NAFLD 88
AFLMixed FL
Increased prevalence of fatty liver in ChinaIncreased prevalence of fatty liver in China
CityCity PeriodPeriod SubjectsSubjects Trend Trend BeijingBeijing 19981998--20032003 Administrative Administrative
officersofficers23 to 2623 to 26
ShanghaiShanghai 19951995--20022002 Factory Factory workersworkers
4 to 144 to 14
WuhanWuhan 19951995--20042004 Office workersOffice workers 125 to 125 to 245245
Fan JG JGH 200722663-8 Wang Z Postgrad Med J 200783192-5 unpublished
Increased prevalence of FL in Shanghai factory Increased prevalence of FL in Shanghai factory
workers between 1995 and 2002workers between 1995 and 2002
0
10
20
30
40
50
60
1995- 1997- 1999- 2001-
Fatty liver
Habitualdrinking
FLAbnormalALT
Obesity
Daibetes
Hypertension
Hyper-TG
Hyper-TC
Fan JG et al J Gastroenterol Hepatol 200722663-68
Incidence of NAFLD in ShanghaiIncidence of NAFLD in Shanghai
5226 non5226 non--drinking workers without USdrinking workers without US--fatty liver at fatty liver at baseline baseline
After 2After 2--year followyear follow--up 310 pts up 310 pts (62) were found to (62) were found to have NAFLD have NAFLD
Incidence of NAFLD Incidence of NAFLD (3 new cases100 people year)(3 new cases100 people year) is equal to is equal to that in that in DionysosDionysos studystudy
The baseline BMI serum triglyceride and their subtle The baseline BMI serum triglyceride and their subtle gain during followgain during follow--up were independent predictors of up were independent predictors of incident of NAFLD incident of NAFLD
Fan et al Hepatol International 2010
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
0
10
20
30
40
16-19 20-29 30-39 40-49 50-59 60-69 70 up
Age
AllMaleFemale
Prevalence of NAFLD increases with age (plt00001) peak 60-69 yrPrevalence of NALFD increases with age in male (p=000011) and female (plt00001)Peak prevalence male 40-49 female 60-69 yr
Fan JG et al J Hepatol 2005
Age- amp sex- related prevalence of fatty liver in Shanghai
Risk factor for fatty liverRisk factor for fatty liver disease disease among Shanghai administrative officersamong Shanghai administrative officers
Risk factorsRisk factors
CCentral obesityentral obesity
ObesityObesity
DyslipidemiaDyslipidemia
DiabetesDiabetes
HypertensionHypertension
Heavy alcohol drinkingHeavy alcohol drinking
Eat or sleep too muchEat or sleep too much
High fat dietHigh fat diet
Physical inactivityPhysical inactivity
Protective factorsProtective factors
ExerciseExercise
Mild alcohol drinkingMild alcohol drinking
Work in moderate stressWork in moderate stress
Fan JG et al Chin J Prev Med 1997 JGH 2013
Criteria for obesity and Criteria for obesity and MetSMetS ethnic differencesethnic differences
Only 2Only 2--3 of Asians 3 of Asians classified as obesity by classified as obesity by Western criteria Western criteria
Compared to Caucasians Compared to Caucasians with same BMI Asian with same BMI Asian people has more visceral people has more visceral fat and less lean body fat and less lean body massmass
Regional criteria of Regional criteria of obesitycentral obesity obesitycentral obesity and and MetSMetS are used in most are used in most Asian studiesAsian studies
IDF Central obesity by waist circumferenceIDF Central obesity by waist circumference
Ethnic groupEthnic group MaleMale FemaleFemale
EuropridsEuroprids 94 cm94 cm 80 cm80 cm
US likelyUS likely 102 cm102 cm 88 cm88 cm
Lancet 2005 3661059
Ethnic groupEthnic group MaleMale FemaleFemale
South Asians South Asians ChineseChinese
90 cm90 cm 80 cm80 cm
JapaneseJapanese 85 cm85 cm 90 cm90 cm
MetSMetS Features in Groups with amp without FLFeatures in Groups with amp without FL
OverweightOverweightObesityObesity
522522 (7897)(7897) 809809 (3218)(3218) 562887562887 lt 00001lt 00001
AbdAbd obesityobesity 474474 (7171)(7171) 662662 (2633)(2633) 468867468867 lt 00001lt 00001
Impaired FGImpaired FG 8181 (1225)(1225) 190190 (756)(756) 1478314783 lt 0001lt 0001
Impaired GTImpaired GT 2525 (378)(378) 2525 (099)(099) 2623326233 lt 00001lt 00001
D MD M 215215 (3253)(3253) 297297 (1181)(1181) 165960165960 lt 00001lt 00001
DyslipidemiaDyslipidemia 467467 (5719)(5719) 999999 (3974)(3974) 4875148751 lt 00001lt 00001
HypertensionHypertension 464464 (7020)(7020) 10711071 (4260)(4260) 159547159547 lt 00001lt 00001
Features Fatty liver n=661 ()
No fatty liver n=2514 ()
T-value p-value
Fan JG et al JGH 2005 201825-32
Less than high Less than high school school educationeducation
306306 (4629)(4629) 825825 (3282)(3282) 4144141441 lt0001lt0001
PovertyPoverty--toto--income income ratiolt1ratiolt1
4949 (741)(741) 245245 (975)(975) 33883388 0065700657
Physical inactivityPhysical inactivity 471471 (7126)(7126) 14721472 (5855)(5855) 3555835558 lt00001lt00001
Current cigarette Current cigarette smokingsmoking
8787 (1316)(1316) 276276 (1098)(1098) 24632463 0116501165
Current habitual Current habitual drinkingdrinking
6161 (923)(923) 181181 (720)(720) 30583058 0080300803
Other Features in Groups with amp without Fatty LiverOther Features in Groups with amp without Fatty LiverFeatures With fatty liver
n=661 ()No fatty liver n=2514 ()
T-value p-value
Fan JG et al J Hepatol 2005 43508-14
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Ultrasound of fatty liverUltrasound of fatty liver
Fatty liver in general population in ChinaFatty liver in general population in China
CityYearCityYear PrevalencePrevalence EtiologyEtiology Others Others Shanghai2005Shanghai2005 173173 NAFL 15 NAFL 15
AFL 08AFL 08Other 12Other 12
Drinking 13Drinking 13
Guangzhou2007Guangzhou2007 145145 NAFL 117NAFL 117AFL 05AFL 05Other 18Other 18
Children 13Children 13
XiXirsquorsquoan2008an2008 136136 NAFL 147NAFL 147AFL 87AFL 87
Drinking 66Drinking 66
Chengdu2009Chengdu2009 125125 NAFL 63 NAFL 63 AFL 26AFL 26Other 36Other 36
Beijing2013Beijing2013 351351 NAFL 313NAFL 313AFL 41AFL 41
Fan J Hepatol 2005 43508-14 Zhou WJG 2007136419-24 Yan Hepatol Int 2008 2S86-S87 Li HBPD Int 20098377-82Yan JGH 2013 281654-9
Prevalence of Fatty Liver in Shanghai Adults Prevalence of Fatty Liver in Shanghai Adults
Total 17Total 17
Male 19 Male 19
Female 15Female 15
NAFLD 15NAFLD 15
AFL 08AFL 08
Mixed FL 12Mixed FL 12
Fan JG et al J Hepatol 2005 43508ndash514
5 7
NAFLD 88
AFLMixed FL
Increased prevalence of fatty liver in ChinaIncreased prevalence of fatty liver in China
CityCity PeriodPeriod SubjectsSubjects Trend Trend BeijingBeijing 19981998--20032003 Administrative Administrative
officersofficers23 to 2623 to 26
ShanghaiShanghai 19951995--20022002 Factory Factory workersworkers
4 to 144 to 14
WuhanWuhan 19951995--20042004 Office workersOffice workers 125 to 125 to 245245
Fan JG JGH 200722663-8 Wang Z Postgrad Med J 200783192-5 unpublished
Increased prevalence of FL in Shanghai factory Increased prevalence of FL in Shanghai factory
workers between 1995 and 2002workers between 1995 and 2002
0
10
20
30
40
50
60
1995- 1997- 1999- 2001-
Fatty liver
Habitualdrinking
FLAbnormalALT
Obesity
Daibetes
Hypertension
Hyper-TG
Hyper-TC
Fan JG et al J Gastroenterol Hepatol 200722663-68
Incidence of NAFLD in ShanghaiIncidence of NAFLD in Shanghai
5226 non5226 non--drinking workers without USdrinking workers without US--fatty liver at fatty liver at baseline baseline
After 2After 2--year followyear follow--up 310 pts up 310 pts (62) were found to (62) were found to have NAFLD have NAFLD
Incidence of NAFLD Incidence of NAFLD (3 new cases100 people year)(3 new cases100 people year) is equal to is equal to that in that in DionysosDionysos studystudy
The baseline BMI serum triglyceride and their subtle The baseline BMI serum triglyceride and their subtle gain during followgain during follow--up were independent predictors of up were independent predictors of incident of NAFLD incident of NAFLD
Fan et al Hepatol International 2010
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
0
10
20
30
40
16-19 20-29 30-39 40-49 50-59 60-69 70 up
Age
AllMaleFemale
Prevalence of NAFLD increases with age (plt00001) peak 60-69 yrPrevalence of NALFD increases with age in male (p=000011) and female (plt00001)Peak prevalence male 40-49 female 60-69 yr
Fan JG et al J Hepatol 2005
Age- amp sex- related prevalence of fatty liver in Shanghai
Risk factor for fatty liverRisk factor for fatty liver disease disease among Shanghai administrative officersamong Shanghai administrative officers
Risk factorsRisk factors
CCentral obesityentral obesity
ObesityObesity
DyslipidemiaDyslipidemia
DiabetesDiabetes
HypertensionHypertension
Heavy alcohol drinkingHeavy alcohol drinking
Eat or sleep too muchEat or sleep too much
High fat dietHigh fat diet
Physical inactivityPhysical inactivity
Protective factorsProtective factors
ExerciseExercise
Mild alcohol drinkingMild alcohol drinking
Work in moderate stressWork in moderate stress
Fan JG et al Chin J Prev Med 1997 JGH 2013
Criteria for obesity and Criteria for obesity and MetSMetS ethnic differencesethnic differences
Only 2Only 2--3 of Asians 3 of Asians classified as obesity by classified as obesity by Western criteria Western criteria
Compared to Caucasians Compared to Caucasians with same BMI Asian with same BMI Asian people has more visceral people has more visceral fat and less lean body fat and less lean body massmass
Regional criteria of Regional criteria of obesitycentral obesity obesitycentral obesity and and MetSMetS are used in most are used in most Asian studiesAsian studies
IDF Central obesity by waist circumferenceIDF Central obesity by waist circumference
Ethnic groupEthnic group MaleMale FemaleFemale
EuropridsEuroprids 94 cm94 cm 80 cm80 cm
US likelyUS likely 102 cm102 cm 88 cm88 cm
Lancet 2005 3661059
Ethnic groupEthnic group MaleMale FemaleFemale
South Asians South Asians ChineseChinese
90 cm90 cm 80 cm80 cm
JapaneseJapanese 85 cm85 cm 90 cm90 cm
MetSMetS Features in Groups with amp without FLFeatures in Groups with amp without FL
OverweightOverweightObesityObesity
522522 (7897)(7897) 809809 (3218)(3218) 562887562887 lt 00001lt 00001
AbdAbd obesityobesity 474474 (7171)(7171) 662662 (2633)(2633) 468867468867 lt 00001lt 00001
Impaired FGImpaired FG 8181 (1225)(1225) 190190 (756)(756) 1478314783 lt 0001lt 0001
Impaired GTImpaired GT 2525 (378)(378) 2525 (099)(099) 2623326233 lt 00001lt 00001
D MD M 215215 (3253)(3253) 297297 (1181)(1181) 165960165960 lt 00001lt 00001
DyslipidemiaDyslipidemia 467467 (5719)(5719) 999999 (3974)(3974) 4875148751 lt 00001lt 00001
HypertensionHypertension 464464 (7020)(7020) 10711071 (4260)(4260) 159547159547 lt 00001lt 00001
Features Fatty liver n=661 ()
No fatty liver n=2514 ()
T-value p-value
Fan JG et al JGH 2005 201825-32
Less than high Less than high school school educationeducation
306306 (4629)(4629) 825825 (3282)(3282) 4144141441 lt0001lt0001
PovertyPoverty--toto--income income ratiolt1ratiolt1
4949 (741)(741) 245245 (975)(975) 33883388 0065700657
Physical inactivityPhysical inactivity 471471 (7126)(7126) 14721472 (5855)(5855) 3555835558 lt00001lt00001
Current cigarette Current cigarette smokingsmoking
8787 (1316)(1316) 276276 (1098)(1098) 24632463 0116501165
Current habitual Current habitual drinkingdrinking
6161 (923)(923) 181181 (720)(720) 30583058 0080300803
Other Features in Groups with amp without Fatty LiverOther Features in Groups with amp without Fatty LiverFeatures With fatty liver
n=661 ()No fatty liver n=2514 ()
T-value p-value
Fan JG et al J Hepatol 2005 43508-14
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Fatty liver in general population in ChinaFatty liver in general population in China
CityYearCityYear PrevalencePrevalence EtiologyEtiology Others Others Shanghai2005Shanghai2005 173173 NAFL 15 NAFL 15
AFL 08AFL 08Other 12Other 12
Drinking 13Drinking 13
Guangzhou2007Guangzhou2007 145145 NAFL 117NAFL 117AFL 05AFL 05Other 18Other 18
Children 13Children 13
XiXirsquorsquoan2008an2008 136136 NAFL 147NAFL 147AFL 87AFL 87
Drinking 66Drinking 66
Chengdu2009Chengdu2009 125125 NAFL 63 NAFL 63 AFL 26AFL 26Other 36Other 36
Beijing2013Beijing2013 351351 NAFL 313NAFL 313AFL 41AFL 41
Fan J Hepatol 2005 43508-14 Zhou WJG 2007136419-24 Yan Hepatol Int 2008 2S86-S87 Li HBPD Int 20098377-82Yan JGH 2013 281654-9
Prevalence of Fatty Liver in Shanghai Adults Prevalence of Fatty Liver in Shanghai Adults
Total 17Total 17
Male 19 Male 19
Female 15Female 15
NAFLD 15NAFLD 15
AFL 08AFL 08
Mixed FL 12Mixed FL 12
Fan JG et al J Hepatol 2005 43508ndash514
5 7
NAFLD 88
AFLMixed FL
Increased prevalence of fatty liver in ChinaIncreased prevalence of fatty liver in China
CityCity PeriodPeriod SubjectsSubjects Trend Trend BeijingBeijing 19981998--20032003 Administrative Administrative
officersofficers23 to 2623 to 26
ShanghaiShanghai 19951995--20022002 Factory Factory workersworkers
4 to 144 to 14
WuhanWuhan 19951995--20042004 Office workersOffice workers 125 to 125 to 245245
Fan JG JGH 200722663-8 Wang Z Postgrad Med J 200783192-5 unpublished
Increased prevalence of FL in Shanghai factory Increased prevalence of FL in Shanghai factory
workers between 1995 and 2002workers between 1995 and 2002
0
10
20
30
40
50
60
1995- 1997- 1999- 2001-
Fatty liver
Habitualdrinking
FLAbnormalALT
Obesity
Daibetes
Hypertension
Hyper-TG
Hyper-TC
Fan JG et al J Gastroenterol Hepatol 200722663-68
Incidence of NAFLD in ShanghaiIncidence of NAFLD in Shanghai
5226 non5226 non--drinking workers without USdrinking workers without US--fatty liver at fatty liver at baseline baseline
After 2After 2--year followyear follow--up 310 pts up 310 pts (62) were found to (62) were found to have NAFLD have NAFLD
Incidence of NAFLD Incidence of NAFLD (3 new cases100 people year)(3 new cases100 people year) is equal to is equal to that in that in DionysosDionysos studystudy
The baseline BMI serum triglyceride and their subtle The baseline BMI serum triglyceride and their subtle gain during followgain during follow--up were independent predictors of up were independent predictors of incident of NAFLD incident of NAFLD
Fan et al Hepatol International 2010
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
0
10
20
30
40
16-19 20-29 30-39 40-49 50-59 60-69 70 up
Age
AllMaleFemale
Prevalence of NAFLD increases with age (plt00001) peak 60-69 yrPrevalence of NALFD increases with age in male (p=000011) and female (plt00001)Peak prevalence male 40-49 female 60-69 yr
Fan JG et al J Hepatol 2005
Age- amp sex- related prevalence of fatty liver in Shanghai
Risk factor for fatty liverRisk factor for fatty liver disease disease among Shanghai administrative officersamong Shanghai administrative officers
Risk factorsRisk factors
CCentral obesityentral obesity
ObesityObesity
DyslipidemiaDyslipidemia
DiabetesDiabetes
HypertensionHypertension
Heavy alcohol drinkingHeavy alcohol drinking
Eat or sleep too muchEat or sleep too much
High fat dietHigh fat diet
Physical inactivityPhysical inactivity
Protective factorsProtective factors
ExerciseExercise
Mild alcohol drinkingMild alcohol drinking
Work in moderate stressWork in moderate stress
Fan JG et al Chin J Prev Med 1997 JGH 2013
Criteria for obesity and Criteria for obesity and MetSMetS ethnic differencesethnic differences
Only 2Only 2--3 of Asians 3 of Asians classified as obesity by classified as obesity by Western criteria Western criteria
Compared to Caucasians Compared to Caucasians with same BMI Asian with same BMI Asian people has more visceral people has more visceral fat and less lean body fat and less lean body massmass
Regional criteria of Regional criteria of obesitycentral obesity obesitycentral obesity and and MetSMetS are used in most are used in most Asian studiesAsian studies
IDF Central obesity by waist circumferenceIDF Central obesity by waist circumference
Ethnic groupEthnic group MaleMale FemaleFemale
EuropridsEuroprids 94 cm94 cm 80 cm80 cm
US likelyUS likely 102 cm102 cm 88 cm88 cm
Lancet 2005 3661059
Ethnic groupEthnic group MaleMale FemaleFemale
South Asians South Asians ChineseChinese
90 cm90 cm 80 cm80 cm
JapaneseJapanese 85 cm85 cm 90 cm90 cm
MetSMetS Features in Groups with amp without FLFeatures in Groups with amp without FL
OverweightOverweightObesityObesity
522522 (7897)(7897) 809809 (3218)(3218) 562887562887 lt 00001lt 00001
AbdAbd obesityobesity 474474 (7171)(7171) 662662 (2633)(2633) 468867468867 lt 00001lt 00001
Impaired FGImpaired FG 8181 (1225)(1225) 190190 (756)(756) 1478314783 lt 0001lt 0001
Impaired GTImpaired GT 2525 (378)(378) 2525 (099)(099) 2623326233 lt 00001lt 00001
D MD M 215215 (3253)(3253) 297297 (1181)(1181) 165960165960 lt 00001lt 00001
DyslipidemiaDyslipidemia 467467 (5719)(5719) 999999 (3974)(3974) 4875148751 lt 00001lt 00001
HypertensionHypertension 464464 (7020)(7020) 10711071 (4260)(4260) 159547159547 lt 00001lt 00001
Features Fatty liver n=661 ()
No fatty liver n=2514 ()
T-value p-value
Fan JG et al JGH 2005 201825-32
Less than high Less than high school school educationeducation
306306 (4629)(4629) 825825 (3282)(3282) 4144141441 lt0001lt0001
PovertyPoverty--toto--income income ratiolt1ratiolt1
4949 (741)(741) 245245 (975)(975) 33883388 0065700657
Physical inactivityPhysical inactivity 471471 (7126)(7126) 14721472 (5855)(5855) 3555835558 lt00001lt00001
Current cigarette Current cigarette smokingsmoking
8787 (1316)(1316) 276276 (1098)(1098) 24632463 0116501165
Current habitual Current habitual drinkingdrinking
6161 (923)(923) 181181 (720)(720) 30583058 0080300803
Other Features in Groups with amp without Fatty LiverOther Features in Groups with amp without Fatty LiverFeatures With fatty liver
n=661 ()No fatty liver n=2514 ()
T-value p-value
Fan JG et al J Hepatol 2005 43508-14
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Prevalence of Fatty Liver in Shanghai Adults Prevalence of Fatty Liver in Shanghai Adults
Total 17Total 17
Male 19 Male 19
Female 15Female 15
NAFLD 15NAFLD 15
AFL 08AFL 08
Mixed FL 12Mixed FL 12
Fan JG et al J Hepatol 2005 43508ndash514
5 7
NAFLD 88
AFLMixed FL
Increased prevalence of fatty liver in ChinaIncreased prevalence of fatty liver in China
CityCity PeriodPeriod SubjectsSubjects Trend Trend BeijingBeijing 19981998--20032003 Administrative Administrative
officersofficers23 to 2623 to 26
ShanghaiShanghai 19951995--20022002 Factory Factory workersworkers
4 to 144 to 14
WuhanWuhan 19951995--20042004 Office workersOffice workers 125 to 125 to 245245
Fan JG JGH 200722663-8 Wang Z Postgrad Med J 200783192-5 unpublished
Increased prevalence of FL in Shanghai factory Increased prevalence of FL in Shanghai factory
workers between 1995 and 2002workers between 1995 and 2002
0
10
20
30
40
50
60
1995- 1997- 1999- 2001-
Fatty liver
Habitualdrinking
FLAbnormalALT
Obesity
Daibetes
Hypertension
Hyper-TG
Hyper-TC
Fan JG et al J Gastroenterol Hepatol 200722663-68
Incidence of NAFLD in ShanghaiIncidence of NAFLD in Shanghai
5226 non5226 non--drinking workers without USdrinking workers without US--fatty liver at fatty liver at baseline baseline
After 2After 2--year followyear follow--up 310 pts up 310 pts (62) were found to (62) were found to have NAFLD have NAFLD
Incidence of NAFLD Incidence of NAFLD (3 new cases100 people year)(3 new cases100 people year) is equal to is equal to that in that in DionysosDionysos studystudy
The baseline BMI serum triglyceride and their subtle The baseline BMI serum triglyceride and their subtle gain during followgain during follow--up were independent predictors of up were independent predictors of incident of NAFLD incident of NAFLD
Fan et al Hepatol International 2010
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
0
10
20
30
40
16-19 20-29 30-39 40-49 50-59 60-69 70 up
Age
AllMaleFemale
Prevalence of NAFLD increases with age (plt00001) peak 60-69 yrPrevalence of NALFD increases with age in male (p=000011) and female (plt00001)Peak prevalence male 40-49 female 60-69 yr
Fan JG et al J Hepatol 2005
Age- amp sex- related prevalence of fatty liver in Shanghai
Risk factor for fatty liverRisk factor for fatty liver disease disease among Shanghai administrative officersamong Shanghai administrative officers
Risk factorsRisk factors
CCentral obesityentral obesity
ObesityObesity
DyslipidemiaDyslipidemia
DiabetesDiabetes
HypertensionHypertension
Heavy alcohol drinkingHeavy alcohol drinking
Eat or sleep too muchEat or sleep too much
High fat dietHigh fat diet
Physical inactivityPhysical inactivity
Protective factorsProtective factors
ExerciseExercise
Mild alcohol drinkingMild alcohol drinking
Work in moderate stressWork in moderate stress
Fan JG et al Chin J Prev Med 1997 JGH 2013
Criteria for obesity and Criteria for obesity and MetSMetS ethnic differencesethnic differences
Only 2Only 2--3 of Asians 3 of Asians classified as obesity by classified as obesity by Western criteria Western criteria
Compared to Caucasians Compared to Caucasians with same BMI Asian with same BMI Asian people has more visceral people has more visceral fat and less lean body fat and less lean body massmass
Regional criteria of Regional criteria of obesitycentral obesity obesitycentral obesity and and MetSMetS are used in most are used in most Asian studiesAsian studies
IDF Central obesity by waist circumferenceIDF Central obesity by waist circumference
Ethnic groupEthnic group MaleMale FemaleFemale
EuropridsEuroprids 94 cm94 cm 80 cm80 cm
US likelyUS likely 102 cm102 cm 88 cm88 cm
Lancet 2005 3661059
Ethnic groupEthnic group MaleMale FemaleFemale
South Asians South Asians ChineseChinese
90 cm90 cm 80 cm80 cm
JapaneseJapanese 85 cm85 cm 90 cm90 cm
MetSMetS Features in Groups with amp without FLFeatures in Groups with amp without FL
OverweightOverweightObesityObesity
522522 (7897)(7897) 809809 (3218)(3218) 562887562887 lt 00001lt 00001
AbdAbd obesityobesity 474474 (7171)(7171) 662662 (2633)(2633) 468867468867 lt 00001lt 00001
Impaired FGImpaired FG 8181 (1225)(1225) 190190 (756)(756) 1478314783 lt 0001lt 0001
Impaired GTImpaired GT 2525 (378)(378) 2525 (099)(099) 2623326233 lt 00001lt 00001
D MD M 215215 (3253)(3253) 297297 (1181)(1181) 165960165960 lt 00001lt 00001
DyslipidemiaDyslipidemia 467467 (5719)(5719) 999999 (3974)(3974) 4875148751 lt 00001lt 00001
HypertensionHypertension 464464 (7020)(7020) 10711071 (4260)(4260) 159547159547 lt 00001lt 00001
Features Fatty liver n=661 ()
No fatty liver n=2514 ()
T-value p-value
Fan JG et al JGH 2005 201825-32
Less than high Less than high school school educationeducation
306306 (4629)(4629) 825825 (3282)(3282) 4144141441 lt0001lt0001
PovertyPoverty--toto--income income ratiolt1ratiolt1
4949 (741)(741) 245245 (975)(975) 33883388 0065700657
Physical inactivityPhysical inactivity 471471 (7126)(7126) 14721472 (5855)(5855) 3555835558 lt00001lt00001
Current cigarette Current cigarette smokingsmoking
8787 (1316)(1316) 276276 (1098)(1098) 24632463 0116501165
Current habitual Current habitual drinkingdrinking
6161 (923)(923) 181181 (720)(720) 30583058 0080300803
Other Features in Groups with amp without Fatty LiverOther Features in Groups with amp without Fatty LiverFeatures With fatty liver
n=661 ()No fatty liver n=2514 ()
T-value p-value
Fan JG et al J Hepatol 2005 43508-14
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Increased prevalence of fatty liver in ChinaIncreased prevalence of fatty liver in China
CityCity PeriodPeriod SubjectsSubjects Trend Trend BeijingBeijing 19981998--20032003 Administrative Administrative
officersofficers23 to 2623 to 26
ShanghaiShanghai 19951995--20022002 Factory Factory workersworkers
4 to 144 to 14
WuhanWuhan 19951995--20042004 Office workersOffice workers 125 to 125 to 245245
Fan JG JGH 200722663-8 Wang Z Postgrad Med J 200783192-5 unpublished
Increased prevalence of FL in Shanghai factory Increased prevalence of FL in Shanghai factory
workers between 1995 and 2002workers between 1995 and 2002
0
10
20
30
40
50
60
1995- 1997- 1999- 2001-
Fatty liver
Habitualdrinking
FLAbnormalALT
Obesity
Daibetes
Hypertension
Hyper-TG
Hyper-TC
Fan JG et al J Gastroenterol Hepatol 200722663-68
Incidence of NAFLD in ShanghaiIncidence of NAFLD in Shanghai
5226 non5226 non--drinking workers without USdrinking workers without US--fatty liver at fatty liver at baseline baseline
After 2After 2--year followyear follow--up 310 pts up 310 pts (62) were found to (62) were found to have NAFLD have NAFLD
Incidence of NAFLD Incidence of NAFLD (3 new cases100 people year)(3 new cases100 people year) is equal to is equal to that in that in DionysosDionysos studystudy
The baseline BMI serum triglyceride and their subtle The baseline BMI serum triglyceride and their subtle gain during followgain during follow--up were independent predictors of up were independent predictors of incident of NAFLD incident of NAFLD
Fan et al Hepatol International 2010
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
0
10
20
30
40
16-19 20-29 30-39 40-49 50-59 60-69 70 up
Age
AllMaleFemale
Prevalence of NAFLD increases with age (plt00001) peak 60-69 yrPrevalence of NALFD increases with age in male (p=000011) and female (plt00001)Peak prevalence male 40-49 female 60-69 yr
Fan JG et al J Hepatol 2005
Age- amp sex- related prevalence of fatty liver in Shanghai
Risk factor for fatty liverRisk factor for fatty liver disease disease among Shanghai administrative officersamong Shanghai administrative officers
Risk factorsRisk factors
CCentral obesityentral obesity
ObesityObesity
DyslipidemiaDyslipidemia
DiabetesDiabetes
HypertensionHypertension
Heavy alcohol drinkingHeavy alcohol drinking
Eat or sleep too muchEat or sleep too much
High fat dietHigh fat diet
Physical inactivityPhysical inactivity
Protective factorsProtective factors
ExerciseExercise
Mild alcohol drinkingMild alcohol drinking
Work in moderate stressWork in moderate stress
Fan JG et al Chin J Prev Med 1997 JGH 2013
Criteria for obesity and Criteria for obesity and MetSMetS ethnic differencesethnic differences
Only 2Only 2--3 of Asians 3 of Asians classified as obesity by classified as obesity by Western criteria Western criteria
Compared to Caucasians Compared to Caucasians with same BMI Asian with same BMI Asian people has more visceral people has more visceral fat and less lean body fat and less lean body massmass
Regional criteria of Regional criteria of obesitycentral obesity obesitycentral obesity and and MetSMetS are used in most are used in most Asian studiesAsian studies
IDF Central obesity by waist circumferenceIDF Central obesity by waist circumference
Ethnic groupEthnic group MaleMale FemaleFemale
EuropridsEuroprids 94 cm94 cm 80 cm80 cm
US likelyUS likely 102 cm102 cm 88 cm88 cm
Lancet 2005 3661059
Ethnic groupEthnic group MaleMale FemaleFemale
South Asians South Asians ChineseChinese
90 cm90 cm 80 cm80 cm
JapaneseJapanese 85 cm85 cm 90 cm90 cm
MetSMetS Features in Groups with amp without FLFeatures in Groups with amp without FL
OverweightOverweightObesityObesity
522522 (7897)(7897) 809809 (3218)(3218) 562887562887 lt 00001lt 00001
AbdAbd obesityobesity 474474 (7171)(7171) 662662 (2633)(2633) 468867468867 lt 00001lt 00001
Impaired FGImpaired FG 8181 (1225)(1225) 190190 (756)(756) 1478314783 lt 0001lt 0001
Impaired GTImpaired GT 2525 (378)(378) 2525 (099)(099) 2623326233 lt 00001lt 00001
D MD M 215215 (3253)(3253) 297297 (1181)(1181) 165960165960 lt 00001lt 00001
DyslipidemiaDyslipidemia 467467 (5719)(5719) 999999 (3974)(3974) 4875148751 lt 00001lt 00001
HypertensionHypertension 464464 (7020)(7020) 10711071 (4260)(4260) 159547159547 lt 00001lt 00001
Features Fatty liver n=661 ()
No fatty liver n=2514 ()
T-value p-value
Fan JG et al JGH 2005 201825-32
Less than high Less than high school school educationeducation
306306 (4629)(4629) 825825 (3282)(3282) 4144141441 lt0001lt0001
PovertyPoverty--toto--income income ratiolt1ratiolt1
4949 (741)(741) 245245 (975)(975) 33883388 0065700657
Physical inactivityPhysical inactivity 471471 (7126)(7126) 14721472 (5855)(5855) 3555835558 lt00001lt00001
Current cigarette Current cigarette smokingsmoking
8787 (1316)(1316) 276276 (1098)(1098) 24632463 0116501165
Current habitual Current habitual drinkingdrinking
6161 (923)(923) 181181 (720)(720) 30583058 0080300803
Other Features in Groups with amp without Fatty LiverOther Features in Groups with amp without Fatty LiverFeatures With fatty liver
n=661 ()No fatty liver n=2514 ()
T-value p-value
Fan JG et al J Hepatol 2005 43508-14
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Increased prevalence of FL in Shanghai factory Increased prevalence of FL in Shanghai factory
workers between 1995 and 2002workers between 1995 and 2002
0
10
20
30
40
50
60
1995- 1997- 1999- 2001-
Fatty liver
Habitualdrinking
FLAbnormalALT
Obesity
Daibetes
Hypertension
Hyper-TG
Hyper-TC
Fan JG et al J Gastroenterol Hepatol 200722663-68
Incidence of NAFLD in ShanghaiIncidence of NAFLD in Shanghai
5226 non5226 non--drinking workers without USdrinking workers without US--fatty liver at fatty liver at baseline baseline
After 2After 2--year followyear follow--up 310 pts up 310 pts (62) were found to (62) were found to have NAFLD have NAFLD
Incidence of NAFLD Incidence of NAFLD (3 new cases100 people year)(3 new cases100 people year) is equal to is equal to that in that in DionysosDionysos studystudy
The baseline BMI serum triglyceride and their subtle The baseline BMI serum triglyceride and their subtle gain during followgain during follow--up were independent predictors of up were independent predictors of incident of NAFLD incident of NAFLD
Fan et al Hepatol International 2010
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
0
10
20
30
40
16-19 20-29 30-39 40-49 50-59 60-69 70 up
Age
AllMaleFemale
Prevalence of NAFLD increases with age (plt00001) peak 60-69 yrPrevalence of NALFD increases with age in male (p=000011) and female (plt00001)Peak prevalence male 40-49 female 60-69 yr
Fan JG et al J Hepatol 2005
Age- amp sex- related prevalence of fatty liver in Shanghai
Risk factor for fatty liverRisk factor for fatty liver disease disease among Shanghai administrative officersamong Shanghai administrative officers
Risk factorsRisk factors
CCentral obesityentral obesity
ObesityObesity
DyslipidemiaDyslipidemia
DiabetesDiabetes
HypertensionHypertension
Heavy alcohol drinkingHeavy alcohol drinking
Eat or sleep too muchEat or sleep too much
High fat dietHigh fat diet
Physical inactivityPhysical inactivity
Protective factorsProtective factors
ExerciseExercise
Mild alcohol drinkingMild alcohol drinking
Work in moderate stressWork in moderate stress
Fan JG et al Chin J Prev Med 1997 JGH 2013
Criteria for obesity and Criteria for obesity and MetSMetS ethnic differencesethnic differences
Only 2Only 2--3 of Asians 3 of Asians classified as obesity by classified as obesity by Western criteria Western criteria
Compared to Caucasians Compared to Caucasians with same BMI Asian with same BMI Asian people has more visceral people has more visceral fat and less lean body fat and less lean body massmass
Regional criteria of Regional criteria of obesitycentral obesity obesitycentral obesity and and MetSMetS are used in most are used in most Asian studiesAsian studies
IDF Central obesity by waist circumferenceIDF Central obesity by waist circumference
Ethnic groupEthnic group MaleMale FemaleFemale
EuropridsEuroprids 94 cm94 cm 80 cm80 cm
US likelyUS likely 102 cm102 cm 88 cm88 cm
Lancet 2005 3661059
Ethnic groupEthnic group MaleMale FemaleFemale
South Asians South Asians ChineseChinese
90 cm90 cm 80 cm80 cm
JapaneseJapanese 85 cm85 cm 90 cm90 cm
MetSMetS Features in Groups with amp without FLFeatures in Groups with amp without FL
OverweightOverweightObesityObesity
522522 (7897)(7897) 809809 (3218)(3218) 562887562887 lt 00001lt 00001
AbdAbd obesityobesity 474474 (7171)(7171) 662662 (2633)(2633) 468867468867 lt 00001lt 00001
Impaired FGImpaired FG 8181 (1225)(1225) 190190 (756)(756) 1478314783 lt 0001lt 0001
Impaired GTImpaired GT 2525 (378)(378) 2525 (099)(099) 2623326233 lt 00001lt 00001
D MD M 215215 (3253)(3253) 297297 (1181)(1181) 165960165960 lt 00001lt 00001
DyslipidemiaDyslipidemia 467467 (5719)(5719) 999999 (3974)(3974) 4875148751 lt 00001lt 00001
HypertensionHypertension 464464 (7020)(7020) 10711071 (4260)(4260) 159547159547 lt 00001lt 00001
Features Fatty liver n=661 ()
No fatty liver n=2514 ()
T-value p-value
Fan JG et al JGH 2005 201825-32
Less than high Less than high school school educationeducation
306306 (4629)(4629) 825825 (3282)(3282) 4144141441 lt0001lt0001
PovertyPoverty--toto--income income ratiolt1ratiolt1
4949 (741)(741) 245245 (975)(975) 33883388 0065700657
Physical inactivityPhysical inactivity 471471 (7126)(7126) 14721472 (5855)(5855) 3555835558 lt00001lt00001
Current cigarette Current cigarette smokingsmoking
8787 (1316)(1316) 276276 (1098)(1098) 24632463 0116501165
Current habitual Current habitual drinkingdrinking
6161 (923)(923) 181181 (720)(720) 30583058 0080300803
Other Features in Groups with amp without Fatty LiverOther Features in Groups with amp without Fatty LiverFeatures With fatty liver
n=661 ()No fatty liver n=2514 ()
T-value p-value
Fan JG et al J Hepatol 2005 43508-14
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Incidence of NAFLD in ShanghaiIncidence of NAFLD in Shanghai
5226 non5226 non--drinking workers without USdrinking workers without US--fatty liver at fatty liver at baseline baseline
After 2After 2--year followyear follow--up 310 pts up 310 pts (62) were found to (62) were found to have NAFLD have NAFLD
Incidence of NAFLD Incidence of NAFLD (3 new cases100 people year)(3 new cases100 people year) is equal to is equal to that in that in DionysosDionysos studystudy
The baseline BMI serum triglyceride and their subtle The baseline BMI serum triglyceride and their subtle gain during followgain during follow--up were independent predictors of up were independent predictors of incident of NAFLD incident of NAFLD
Fan et al Hepatol International 2010
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
0
10
20
30
40
16-19 20-29 30-39 40-49 50-59 60-69 70 up
Age
AllMaleFemale
Prevalence of NAFLD increases with age (plt00001) peak 60-69 yrPrevalence of NALFD increases with age in male (p=000011) and female (plt00001)Peak prevalence male 40-49 female 60-69 yr
Fan JG et al J Hepatol 2005
Age- amp sex- related prevalence of fatty liver in Shanghai
Risk factor for fatty liverRisk factor for fatty liver disease disease among Shanghai administrative officersamong Shanghai administrative officers
Risk factorsRisk factors
CCentral obesityentral obesity
ObesityObesity
DyslipidemiaDyslipidemia
DiabetesDiabetes
HypertensionHypertension
Heavy alcohol drinkingHeavy alcohol drinking
Eat or sleep too muchEat or sleep too much
High fat dietHigh fat diet
Physical inactivityPhysical inactivity
Protective factorsProtective factors
ExerciseExercise
Mild alcohol drinkingMild alcohol drinking
Work in moderate stressWork in moderate stress
Fan JG et al Chin J Prev Med 1997 JGH 2013
Criteria for obesity and Criteria for obesity and MetSMetS ethnic differencesethnic differences
Only 2Only 2--3 of Asians 3 of Asians classified as obesity by classified as obesity by Western criteria Western criteria
Compared to Caucasians Compared to Caucasians with same BMI Asian with same BMI Asian people has more visceral people has more visceral fat and less lean body fat and less lean body massmass
Regional criteria of Regional criteria of obesitycentral obesity obesitycentral obesity and and MetSMetS are used in most are used in most Asian studiesAsian studies
IDF Central obesity by waist circumferenceIDF Central obesity by waist circumference
Ethnic groupEthnic group MaleMale FemaleFemale
EuropridsEuroprids 94 cm94 cm 80 cm80 cm
US likelyUS likely 102 cm102 cm 88 cm88 cm
Lancet 2005 3661059
Ethnic groupEthnic group MaleMale FemaleFemale
South Asians South Asians ChineseChinese
90 cm90 cm 80 cm80 cm
JapaneseJapanese 85 cm85 cm 90 cm90 cm
MetSMetS Features in Groups with amp without FLFeatures in Groups with amp without FL
OverweightOverweightObesityObesity
522522 (7897)(7897) 809809 (3218)(3218) 562887562887 lt 00001lt 00001
AbdAbd obesityobesity 474474 (7171)(7171) 662662 (2633)(2633) 468867468867 lt 00001lt 00001
Impaired FGImpaired FG 8181 (1225)(1225) 190190 (756)(756) 1478314783 lt 0001lt 0001
Impaired GTImpaired GT 2525 (378)(378) 2525 (099)(099) 2623326233 lt 00001lt 00001
D MD M 215215 (3253)(3253) 297297 (1181)(1181) 165960165960 lt 00001lt 00001
DyslipidemiaDyslipidemia 467467 (5719)(5719) 999999 (3974)(3974) 4875148751 lt 00001lt 00001
HypertensionHypertension 464464 (7020)(7020) 10711071 (4260)(4260) 159547159547 lt 00001lt 00001
Features Fatty liver n=661 ()
No fatty liver n=2514 ()
T-value p-value
Fan JG et al JGH 2005 201825-32
Less than high Less than high school school educationeducation
306306 (4629)(4629) 825825 (3282)(3282) 4144141441 lt0001lt0001
PovertyPoverty--toto--income income ratiolt1ratiolt1
4949 (741)(741) 245245 (975)(975) 33883388 0065700657
Physical inactivityPhysical inactivity 471471 (7126)(7126) 14721472 (5855)(5855) 3555835558 lt00001lt00001
Current cigarette Current cigarette smokingsmoking
8787 (1316)(1316) 276276 (1098)(1098) 24632463 0116501165
Current habitual Current habitual drinkingdrinking
6161 (923)(923) 181181 (720)(720) 30583058 0080300803
Other Features in Groups with amp without Fatty LiverOther Features in Groups with amp without Fatty LiverFeatures With fatty liver
n=661 ()No fatty liver n=2514 ()
T-value p-value
Fan JG et al J Hepatol 2005 43508-14
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
0
10
20
30
40
16-19 20-29 30-39 40-49 50-59 60-69 70 up
Age
AllMaleFemale
Prevalence of NAFLD increases with age (plt00001) peak 60-69 yrPrevalence of NALFD increases with age in male (p=000011) and female (plt00001)Peak prevalence male 40-49 female 60-69 yr
Fan JG et al J Hepatol 2005
Age- amp sex- related prevalence of fatty liver in Shanghai
Risk factor for fatty liverRisk factor for fatty liver disease disease among Shanghai administrative officersamong Shanghai administrative officers
Risk factorsRisk factors
CCentral obesityentral obesity
ObesityObesity
DyslipidemiaDyslipidemia
DiabetesDiabetes
HypertensionHypertension
Heavy alcohol drinkingHeavy alcohol drinking
Eat or sleep too muchEat or sleep too much
High fat dietHigh fat diet
Physical inactivityPhysical inactivity
Protective factorsProtective factors
ExerciseExercise
Mild alcohol drinkingMild alcohol drinking
Work in moderate stressWork in moderate stress
Fan JG et al Chin J Prev Med 1997 JGH 2013
Criteria for obesity and Criteria for obesity and MetSMetS ethnic differencesethnic differences
Only 2Only 2--3 of Asians 3 of Asians classified as obesity by classified as obesity by Western criteria Western criteria
Compared to Caucasians Compared to Caucasians with same BMI Asian with same BMI Asian people has more visceral people has more visceral fat and less lean body fat and less lean body massmass
Regional criteria of Regional criteria of obesitycentral obesity obesitycentral obesity and and MetSMetS are used in most are used in most Asian studiesAsian studies
IDF Central obesity by waist circumferenceIDF Central obesity by waist circumference
Ethnic groupEthnic group MaleMale FemaleFemale
EuropridsEuroprids 94 cm94 cm 80 cm80 cm
US likelyUS likely 102 cm102 cm 88 cm88 cm
Lancet 2005 3661059
Ethnic groupEthnic group MaleMale FemaleFemale
South Asians South Asians ChineseChinese
90 cm90 cm 80 cm80 cm
JapaneseJapanese 85 cm85 cm 90 cm90 cm
MetSMetS Features in Groups with amp without FLFeatures in Groups with amp without FL
OverweightOverweightObesityObesity
522522 (7897)(7897) 809809 (3218)(3218) 562887562887 lt 00001lt 00001
AbdAbd obesityobesity 474474 (7171)(7171) 662662 (2633)(2633) 468867468867 lt 00001lt 00001
Impaired FGImpaired FG 8181 (1225)(1225) 190190 (756)(756) 1478314783 lt 0001lt 0001
Impaired GTImpaired GT 2525 (378)(378) 2525 (099)(099) 2623326233 lt 00001lt 00001
D MD M 215215 (3253)(3253) 297297 (1181)(1181) 165960165960 lt 00001lt 00001
DyslipidemiaDyslipidemia 467467 (5719)(5719) 999999 (3974)(3974) 4875148751 lt 00001lt 00001
HypertensionHypertension 464464 (7020)(7020) 10711071 (4260)(4260) 159547159547 lt 00001lt 00001
Features Fatty liver n=661 ()
No fatty liver n=2514 ()
T-value p-value
Fan JG et al JGH 2005 201825-32
Less than high Less than high school school educationeducation
306306 (4629)(4629) 825825 (3282)(3282) 4144141441 lt0001lt0001
PovertyPoverty--toto--income income ratiolt1ratiolt1
4949 (741)(741) 245245 (975)(975) 33883388 0065700657
Physical inactivityPhysical inactivity 471471 (7126)(7126) 14721472 (5855)(5855) 3555835558 lt00001lt00001
Current cigarette Current cigarette smokingsmoking
8787 (1316)(1316) 276276 (1098)(1098) 24632463 0116501165
Current habitual Current habitual drinkingdrinking
6161 (923)(923) 181181 (720)(720) 30583058 0080300803
Other Features in Groups with amp without Fatty LiverOther Features in Groups with amp without Fatty LiverFeatures With fatty liver
n=661 ()No fatty liver n=2514 ()
T-value p-value
Fan JG et al J Hepatol 2005 43508-14
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
0
10
20
30
40
16-19 20-29 30-39 40-49 50-59 60-69 70 up
Age
AllMaleFemale
Prevalence of NAFLD increases with age (plt00001) peak 60-69 yrPrevalence of NALFD increases with age in male (p=000011) and female (plt00001)Peak prevalence male 40-49 female 60-69 yr
Fan JG et al J Hepatol 2005
Age- amp sex- related prevalence of fatty liver in Shanghai
Risk factor for fatty liverRisk factor for fatty liver disease disease among Shanghai administrative officersamong Shanghai administrative officers
Risk factorsRisk factors
CCentral obesityentral obesity
ObesityObesity
DyslipidemiaDyslipidemia
DiabetesDiabetes
HypertensionHypertension
Heavy alcohol drinkingHeavy alcohol drinking
Eat or sleep too muchEat or sleep too much
High fat dietHigh fat diet
Physical inactivityPhysical inactivity
Protective factorsProtective factors
ExerciseExercise
Mild alcohol drinkingMild alcohol drinking
Work in moderate stressWork in moderate stress
Fan JG et al Chin J Prev Med 1997 JGH 2013
Criteria for obesity and Criteria for obesity and MetSMetS ethnic differencesethnic differences
Only 2Only 2--3 of Asians 3 of Asians classified as obesity by classified as obesity by Western criteria Western criteria
Compared to Caucasians Compared to Caucasians with same BMI Asian with same BMI Asian people has more visceral people has more visceral fat and less lean body fat and less lean body massmass
Regional criteria of Regional criteria of obesitycentral obesity obesitycentral obesity and and MetSMetS are used in most are used in most Asian studiesAsian studies
IDF Central obesity by waist circumferenceIDF Central obesity by waist circumference
Ethnic groupEthnic group MaleMale FemaleFemale
EuropridsEuroprids 94 cm94 cm 80 cm80 cm
US likelyUS likely 102 cm102 cm 88 cm88 cm
Lancet 2005 3661059
Ethnic groupEthnic group MaleMale FemaleFemale
South Asians South Asians ChineseChinese
90 cm90 cm 80 cm80 cm
JapaneseJapanese 85 cm85 cm 90 cm90 cm
MetSMetS Features in Groups with amp without FLFeatures in Groups with amp without FL
OverweightOverweightObesityObesity
522522 (7897)(7897) 809809 (3218)(3218) 562887562887 lt 00001lt 00001
AbdAbd obesityobesity 474474 (7171)(7171) 662662 (2633)(2633) 468867468867 lt 00001lt 00001
Impaired FGImpaired FG 8181 (1225)(1225) 190190 (756)(756) 1478314783 lt 0001lt 0001
Impaired GTImpaired GT 2525 (378)(378) 2525 (099)(099) 2623326233 lt 00001lt 00001
D MD M 215215 (3253)(3253) 297297 (1181)(1181) 165960165960 lt 00001lt 00001
DyslipidemiaDyslipidemia 467467 (5719)(5719) 999999 (3974)(3974) 4875148751 lt 00001lt 00001
HypertensionHypertension 464464 (7020)(7020) 10711071 (4260)(4260) 159547159547 lt 00001lt 00001
Features Fatty liver n=661 ()
No fatty liver n=2514 ()
T-value p-value
Fan JG et al JGH 2005 201825-32
Less than high Less than high school school educationeducation
306306 (4629)(4629) 825825 (3282)(3282) 4144141441 lt0001lt0001
PovertyPoverty--toto--income income ratiolt1ratiolt1
4949 (741)(741) 245245 (975)(975) 33883388 0065700657
Physical inactivityPhysical inactivity 471471 (7126)(7126) 14721472 (5855)(5855) 3555835558 lt00001lt00001
Current cigarette Current cigarette smokingsmoking
8787 (1316)(1316) 276276 (1098)(1098) 24632463 0116501165
Current habitual Current habitual drinkingdrinking
6161 (923)(923) 181181 (720)(720) 30583058 0080300803
Other Features in Groups with amp without Fatty LiverOther Features in Groups with amp without Fatty LiverFeatures With fatty liver
n=661 ()No fatty liver n=2514 ()
T-value p-value
Fan JG et al J Hepatol 2005 43508-14
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Risk factor for fatty liverRisk factor for fatty liver disease disease among Shanghai administrative officersamong Shanghai administrative officers
Risk factorsRisk factors
CCentral obesityentral obesity
ObesityObesity
DyslipidemiaDyslipidemia
DiabetesDiabetes
HypertensionHypertension
Heavy alcohol drinkingHeavy alcohol drinking
Eat or sleep too muchEat or sleep too much
High fat dietHigh fat diet
Physical inactivityPhysical inactivity
Protective factorsProtective factors
ExerciseExercise
Mild alcohol drinkingMild alcohol drinking
Work in moderate stressWork in moderate stress
Fan JG et al Chin J Prev Med 1997 JGH 2013
Criteria for obesity and Criteria for obesity and MetSMetS ethnic differencesethnic differences
Only 2Only 2--3 of Asians 3 of Asians classified as obesity by classified as obesity by Western criteria Western criteria
Compared to Caucasians Compared to Caucasians with same BMI Asian with same BMI Asian people has more visceral people has more visceral fat and less lean body fat and less lean body massmass
Regional criteria of Regional criteria of obesitycentral obesity obesitycentral obesity and and MetSMetS are used in most are used in most Asian studiesAsian studies
IDF Central obesity by waist circumferenceIDF Central obesity by waist circumference
Ethnic groupEthnic group MaleMale FemaleFemale
EuropridsEuroprids 94 cm94 cm 80 cm80 cm
US likelyUS likely 102 cm102 cm 88 cm88 cm
Lancet 2005 3661059
Ethnic groupEthnic group MaleMale FemaleFemale
South Asians South Asians ChineseChinese
90 cm90 cm 80 cm80 cm
JapaneseJapanese 85 cm85 cm 90 cm90 cm
MetSMetS Features in Groups with amp without FLFeatures in Groups with amp without FL
OverweightOverweightObesityObesity
522522 (7897)(7897) 809809 (3218)(3218) 562887562887 lt 00001lt 00001
AbdAbd obesityobesity 474474 (7171)(7171) 662662 (2633)(2633) 468867468867 lt 00001lt 00001
Impaired FGImpaired FG 8181 (1225)(1225) 190190 (756)(756) 1478314783 lt 0001lt 0001
Impaired GTImpaired GT 2525 (378)(378) 2525 (099)(099) 2623326233 lt 00001lt 00001
D MD M 215215 (3253)(3253) 297297 (1181)(1181) 165960165960 lt 00001lt 00001
DyslipidemiaDyslipidemia 467467 (5719)(5719) 999999 (3974)(3974) 4875148751 lt 00001lt 00001
HypertensionHypertension 464464 (7020)(7020) 10711071 (4260)(4260) 159547159547 lt 00001lt 00001
Features Fatty liver n=661 ()
No fatty liver n=2514 ()
T-value p-value
Fan JG et al JGH 2005 201825-32
Less than high Less than high school school educationeducation
306306 (4629)(4629) 825825 (3282)(3282) 4144141441 lt0001lt0001
PovertyPoverty--toto--income income ratiolt1ratiolt1
4949 (741)(741) 245245 (975)(975) 33883388 0065700657
Physical inactivityPhysical inactivity 471471 (7126)(7126) 14721472 (5855)(5855) 3555835558 lt00001lt00001
Current cigarette Current cigarette smokingsmoking
8787 (1316)(1316) 276276 (1098)(1098) 24632463 0116501165
Current habitual Current habitual drinkingdrinking
6161 (923)(923) 181181 (720)(720) 30583058 0080300803
Other Features in Groups with amp without Fatty LiverOther Features in Groups with amp without Fatty LiverFeatures With fatty liver
n=661 ()No fatty liver n=2514 ()
T-value p-value
Fan JG et al J Hepatol 2005 43508-14
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Criteria for obesity and Criteria for obesity and MetSMetS ethnic differencesethnic differences
Only 2Only 2--3 of Asians 3 of Asians classified as obesity by classified as obesity by Western criteria Western criteria
Compared to Caucasians Compared to Caucasians with same BMI Asian with same BMI Asian people has more visceral people has more visceral fat and less lean body fat and less lean body massmass
Regional criteria of Regional criteria of obesitycentral obesity obesitycentral obesity and and MetSMetS are used in most are used in most Asian studiesAsian studies
IDF Central obesity by waist circumferenceIDF Central obesity by waist circumference
Ethnic groupEthnic group MaleMale FemaleFemale
EuropridsEuroprids 94 cm94 cm 80 cm80 cm
US likelyUS likely 102 cm102 cm 88 cm88 cm
Lancet 2005 3661059
Ethnic groupEthnic group MaleMale FemaleFemale
South Asians South Asians ChineseChinese
90 cm90 cm 80 cm80 cm
JapaneseJapanese 85 cm85 cm 90 cm90 cm
MetSMetS Features in Groups with amp without FLFeatures in Groups with amp without FL
OverweightOverweightObesityObesity
522522 (7897)(7897) 809809 (3218)(3218) 562887562887 lt 00001lt 00001
AbdAbd obesityobesity 474474 (7171)(7171) 662662 (2633)(2633) 468867468867 lt 00001lt 00001
Impaired FGImpaired FG 8181 (1225)(1225) 190190 (756)(756) 1478314783 lt 0001lt 0001
Impaired GTImpaired GT 2525 (378)(378) 2525 (099)(099) 2623326233 lt 00001lt 00001
D MD M 215215 (3253)(3253) 297297 (1181)(1181) 165960165960 lt 00001lt 00001
DyslipidemiaDyslipidemia 467467 (5719)(5719) 999999 (3974)(3974) 4875148751 lt 00001lt 00001
HypertensionHypertension 464464 (7020)(7020) 10711071 (4260)(4260) 159547159547 lt 00001lt 00001
Features Fatty liver n=661 ()
No fatty liver n=2514 ()
T-value p-value
Fan JG et al JGH 2005 201825-32
Less than high Less than high school school educationeducation
306306 (4629)(4629) 825825 (3282)(3282) 4144141441 lt0001lt0001
PovertyPoverty--toto--income income ratiolt1ratiolt1
4949 (741)(741) 245245 (975)(975) 33883388 0065700657
Physical inactivityPhysical inactivity 471471 (7126)(7126) 14721472 (5855)(5855) 3555835558 lt00001lt00001
Current cigarette Current cigarette smokingsmoking
8787 (1316)(1316) 276276 (1098)(1098) 24632463 0116501165
Current habitual Current habitual drinkingdrinking
6161 (923)(923) 181181 (720)(720) 30583058 0080300803
Other Features in Groups with amp without Fatty LiverOther Features in Groups with amp without Fatty LiverFeatures With fatty liver
n=661 ()No fatty liver n=2514 ()
T-value p-value
Fan JG et al J Hepatol 2005 43508-14
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
IDF Central obesity by waist circumferenceIDF Central obesity by waist circumference
Ethnic groupEthnic group MaleMale FemaleFemale
EuropridsEuroprids 94 cm94 cm 80 cm80 cm
US likelyUS likely 102 cm102 cm 88 cm88 cm
Lancet 2005 3661059
Ethnic groupEthnic group MaleMale FemaleFemale
South Asians South Asians ChineseChinese
90 cm90 cm 80 cm80 cm
JapaneseJapanese 85 cm85 cm 90 cm90 cm
MetSMetS Features in Groups with amp without FLFeatures in Groups with amp without FL
OverweightOverweightObesityObesity
522522 (7897)(7897) 809809 (3218)(3218) 562887562887 lt 00001lt 00001
AbdAbd obesityobesity 474474 (7171)(7171) 662662 (2633)(2633) 468867468867 lt 00001lt 00001
Impaired FGImpaired FG 8181 (1225)(1225) 190190 (756)(756) 1478314783 lt 0001lt 0001
Impaired GTImpaired GT 2525 (378)(378) 2525 (099)(099) 2623326233 lt 00001lt 00001
D MD M 215215 (3253)(3253) 297297 (1181)(1181) 165960165960 lt 00001lt 00001
DyslipidemiaDyslipidemia 467467 (5719)(5719) 999999 (3974)(3974) 4875148751 lt 00001lt 00001
HypertensionHypertension 464464 (7020)(7020) 10711071 (4260)(4260) 159547159547 lt 00001lt 00001
Features Fatty liver n=661 ()
No fatty liver n=2514 ()
T-value p-value
Fan JG et al JGH 2005 201825-32
Less than high Less than high school school educationeducation
306306 (4629)(4629) 825825 (3282)(3282) 4144141441 lt0001lt0001
PovertyPoverty--toto--income income ratiolt1ratiolt1
4949 (741)(741) 245245 (975)(975) 33883388 0065700657
Physical inactivityPhysical inactivity 471471 (7126)(7126) 14721472 (5855)(5855) 3555835558 lt00001lt00001
Current cigarette Current cigarette smokingsmoking
8787 (1316)(1316) 276276 (1098)(1098) 24632463 0116501165
Current habitual Current habitual drinkingdrinking
6161 (923)(923) 181181 (720)(720) 30583058 0080300803
Other Features in Groups with amp without Fatty LiverOther Features in Groups with amp without Fatty LiverFeatures With fatty liver
n=661 ()No fatty liver n=2514 ()
T-value p-value
Fan JG et al J Hepatol 2005 43508-14
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
MetSMetS Features in Groups with amp without FLFeatures in Groups with amp without FL
OverweightOverweightObesityObesity
522522 (7897)(7897) 809809 (3218)(3218) 562887562887 lt 00001lt 00001
AbdAbd obesityobesity 474474 (7171)(7171) 662662 (2633)(2633) 468867468867 lt 00001lt 00001
Impaired FGImpaired FG 8181 (1225)(1225) 190190 (756)(756) 1478314783 lt 0001lt 0001
Impaired GTImpaired GT 2525 (378)(378) 2525 (099)(099) 2623326233 lt 00001lt 00001
D MD M 215215 (3253)(3253) 297297 (1181)(1181) 165960165960 lt 00001lt 00001
DyslipidemiaDyslipidemia 467467 (5719)(5719) 999999 (3974)(3974) 4875148751 lt 00001lt 00001
HypertensionHypertension 464464 (7020)(7020) 10711071 (4260)(4260) 159547159547 lt 00001lt 00001
Features Fatty liver n=661 ()
No fatty liver n=2514 ()
T-value p-value
Fan JG et al JGH 2005 201825-32
Less than high Less than high school school educationeducation
306306 (4629)(4629) 825825 (3282)(3282) 4144141441 lt0001lt0001
PovertyPoverty--toto--income income ratiolt1ratiolt1
4949 (741)(741) 245245 (975)(975) 33883388 0065700657
Physical inactivityPhysical inactivity 471471 (7126)(7126) 14721472 (5855)(5855) 3555835558 lt00001lt00001
Current cigarette Current cigarette smokingsmoking
8787 (1316)(1316) 276276 (1098)(1098) 24632463 0116501165
Current habitual Current habitual drinkingdrinking
6161 (923)(923) 181181 (720)(720) 30583058 0080300803
Other Features in Groups with amp without Fatty LiverOther Features in Groups with amp without Fatty LiverFeatures With fatty liver
n=661 ()No fatty liver n=2514 ()
T-value p-value
Fan JG et al J Hepatol 2005 43508-14
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Less than high Less than high school school educationeducation
306306 (4629)(4629) 825825 (3282)(3282) 4144141441 lt0001lt0001
PovertyPoverty--toto--income income ratiolt1ratiolt1
4949 (741)(741) 245245 (975)(975) 33883388 0065700657
Physical inactivityPhysical inactivity 471471 (7126)(7126) 14721472 (5855)(5855) 3555835558 lt00001lt00001
Current cigarette Current cigarette smokingsmoking
8787 (1316)(1316) 276276 (1098)(1098) 24632463 0116501165
Current habitual Current habitual drinkingdrinking
6161 (923)(923) 181181 (720)(720) 30583058 0080300803
Other Features in Groups with amp without Fatty LiverOther Features in Groups with amp without Fatty LiverFeatures With fatty liver
n=661 ()No fatty liver n=2514 ()
T-value p-value
Fan JG et al J Hepatol 2005 43508-14
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Fan JG WJG2008 142418-24
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Group (n) Fatty liver()
Odds Ratio (95 CI)
Control Obesity Drinking
Control (1049)
35 (3)
Excessive drinking (25)
3 (8)
4(11-12)
Obesity (1252)
484 (39)
12(8-17)
3(11-10)
Obesity+ drinking (35)
20 (57)
17(9-32)
5(14-17)
15(09-26)
FL more closely related to obesity than alcoholism
Fan JG et al J Hepatol 200543508-514
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with incidence of NAFLDchanges with incidence of NAFLD
Among 5194 subjects Among 5194 subjects without NAFLD at without NAFLD at baseline 327 (63) baseline 327 (63) developed NAFLD over developed NAFLD over 2 years 2 years
Incident of NAFLD Incident of NAFLD during followduring follow--up was up was related to BMI and related to BMI and serum TG elevations serum TG elevations
-20
-15
-10
-5
0
5
10
15
20
25
30
lt 23 23-25 25-30 gt 30
Incidence of FL
Changes of BMIwith FL
Changes of BMIwithout FL
Fan JG et al Chin J Hepatol 2010
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Relationship of BMI at baseline and its Relationship of BMI at baseline and its changes with remission rate of NAFLDchanges with remission rate of NAFLD
440 subjects with NAFLD 440 subjects with NAFLD at baseline 60 (136) at baseline 60 (136) showed regression at the showed regression at the end of 2end of 2--year followyear follow--upup
Multiple regression analysis Multiple regression analysis showed that NAFLD showed that NAFLD regression associated with regression associated with BMI serum TG level at BMI serum TG level at baseline baseline
and the decreased rate of and the decreased rate of BMI and serum TG level BMI and serum TG level during followduring follow--up up -10
-5
0
5
10
15
20
lt 23 23-25 25-30 gt 30
Remission rate ofFL
Changes of BMIwith FL remission
Changes of BMIpersistent withFL
Zhou C and Fan JG Chin J Intern Med 2012
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Hepatitis B and fatty liver Hepatitis B and fatty liver Causal or coincidentalCausal or coincidental
CHB is the most common etiologic agents of liver CHB is the most common etiologic agents of liver disease in Chinadisease in China
Unlike CHC hepatic Unlike CHC hepatic steatosissteatosis is not commonly is not commonly observed among pts with CHB observed among pts with CHB
Prevalence of Prevalence of histopathologicalhistopathological steatosissteatosis in pts with in pts with CHB is around 28 CHB is around 28 (12(12--76) and increased with the epidemic of 76) and increased with the epidemic of
obesityobesity
Hepatic Hepatic steatosissteatosis in CHB associated with metabolic in CHB associated with metabolic factors not viral onesfactors not viral ones
MetSMetS and and steatosissteatosis seem to increase risk of cirrhosis and HCC in pts with CHBseem to increase risk of cirrhosis and HCC in pts with CHB
Fan JG et al JGH 200823679-81
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Prevalence and predictors of steatosis in CHBPrevalence and predictors of steatosis in CHBAuthorsAuthors Country Country nn SteatosisSteatosis PredictorsPredictors
CzajaCzaja et al 1998et al 1998AltiparmakAltiparmak 20052005Gordon 2005Gordon 2005ThomopoulosThomopoulos 20062006BondiniBondini et al 2007et al 2007CindorukCindoruk et al 2007et al 2007TsochatrizTsochatriz et 2007et 2007Chu et al 2007Chu et al 2007Wang et al 2008Wang et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009MinakariMinakari 20092009PersicoPersico M 2009M 2009
USAUSATurkeyTurkeyAustraliaAustraliaGreeceGreeceUSAUSATurkeyTurkeyGreeceGreeceTaiwanTaiwanTaiwanTaiwanChina China (Shanghai)(Shanghai)
China China (Beijing)(Beijing)
KoreaKoreaIranIranItalyItaly
18181641641717
2332336464
14014021321350505858
191519151531538686
132132126126
22223939767618181919343459595656333314142727515142421212
Not reported BMIgt28 diabetesNot reported BMIgt28 diabetesOlder age BMI Older age BMI dyslipidemiadyslipidemiaWaist circumference FBG Waist circumference FBG cc--peptidpeptidFBG BMIFBG BMIAge obesity Age obesity hypertensiondyslipidemiahypertensiondyslipidemiaBMI cholesterol triglycerideBMI cholesterol triglycerideBMI diabetesBMI diabetesBMI HOMABMI HOMA--IR triglycerideIR triglycerideBMIBMIBMI BMI TGTG AApo B uric acid FBGpo B uric acid FBGAge BMI insulin HOMAAge BMI insulin HOMA--IR IR Tocal Tocal cholesterol triglyceridecholesterol triglycerideBMI triglyceride FBG GGTBMI triglyceride FBG GGTgt30 BMI agegt30 BMI age
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Steatosis in CHB lack of associations with Steatosis in CHB lack of associations with HBV replication and disease severityHBV replication and disease severity
AuthorsAuthors Association with Association with HBeAgHBeAg or or HBV DNAHBV DNA
Worsens fibrosis Worsens fibrosis severityseverity
ElloumiElloumi et al 2008et al 2008Shi et al 2008Shi et al 2008PengPeng et al 2008et al 2008YunYun et al 2009et al 2009Kumar et al 2009Kumar et al 2009MinakariMinakari et al 2009et al 2009PersicoPersico et al 2009et al 2009
NoNoNoNoNoNoNoNoNoNoNoNo
Not mentionedNot mentioned
No No NoNoNoNoNoNoNoNoNoNoNoNo
Park et al 2009Park et al 2009 insulin resistance not associated with histological insulin resistance not associated with histological severityseverity
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Fatty liver amp HBV infection in ChineseFatty liver amp HBV infection in Chinese
Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei
Fan JG et al World J Gastroenterol 2003 Cheng YL et al Plos One 2013
Inverse association between HBV infection and Inverse association between HBV infection and MRSMRS--diagnosed fatty liver diagnosed fatty liver in Hong Kong adultsin Hong Kong adults Wong VWS et al J Hepatol 2012
Inverse association between HBV infection and metabolic syndrome Luo et al Clin Chim Acta 2007 Jan et al Int J Obes 2006 Wong et al J Hepatol 2012
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
SSteatosisteatosis prevalent in CHB and prevalent in CHB and negative negative associated with associated with virologicalvirological factorsfactors
Prevalence of steatosis in patients with CHB infection
0
5
10
15
20
25
30
35
40
45
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
time
prevalence
steatosis 1-4 steatosis ≧ 5
3212 pts (2574 men) with3212 pts (2574 men) with biopsybiopsy--proven CHBproven CHB at at ShundeShunde Hospital between Hospital between 2002 and 2011 were analyzed 2002 and 2011 were analyzed
SSteatosisteatosis was present in 554 (17was present in 554 (1733) pts with annual prevalence increased ) pts with annual prevalence increased over timeover time
Compared to pts without Compared to pts without steatosissteatosis percentage of percentage of serum serum HBeAgHBeAg--positive positive and detectable HBV DNA and and detectable HBV DNA and intrahepaticintrahepatic HBsAgHBsAg-- and and HBcAgHBcAg--positive positive staining were decreased in staining were decreased in steatosissteatosis ptspts
IntrahepaticIntrahepatic HBsAgHBsAg--positive stainingpositive staining isis an independent factor associated an independent factor associated with lower risk of with lower risk of steatosissteatosis iin multivariate n multivariate analysisanalysis
Wang GS and Fan JG J Dig Dis under review
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Is Is steatosissteatosis good or bad to CHBgood or bad to CHB
Hepatic Hepatic steatosissteatosis contribute to contribute to seroclearanceseroclearance of of HBsAgHBsAg in chronic HBV infection in chronic HBV infection Chu CM et al Chu CM et al IntInt J J ObesObes ((LondLond)) 200731871200731871--5Dig 5Dig DisDis SciSci 20132013
MetSMetS increase risk of advanced fibrosis in patients increase risk of advanced fibrosis in patients with CHB infection with CHB infection Shi and Fan Chin J Diabetes 2009Shi and Fan Chin J Diabetes 2009
MetSMetS increase risk of cirrhosis in patients with increase risk of cirrhosis in patients with chronic hepatitis B chronic hepatitis B Wong et al Wong et al GutGut 200958111200958111--77
T2DM increase risk of HCC in chronic hepatitis B T2DM increase risk of HCC in chronic hepatitis B Yu et al J Yu et al J ClinClin OncolOncol 2008 2655762008 265576--8282
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Ye DW et alAASLD2009
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Epidemiology of FLD in ChinaEpidemiology of FLD in China
Prevalence of FLDPrevalence of FLD
Risk factors of FLDRisk factors of FLD
NAFLD and CHBNAFLD and CHB
Clinical settings of NAFLDClinical settings of NAFLD
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Etiologies of CLD in Chinese outEtiologies of CLD in Chinese out--patientspatients
Etiologies of 6106 pts with CLDin Hong Kong
894
51
17
15
13
0 20 40 60 80 100
CHB
CHC
ALD
NAFLD
PBC
Fung KT et al Eur J Gastroenterol Hepatol 200719659-64
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Etiology of fatty liver in liver clinic in ShanghaiEtiology of fatty liver in liver clinic in Shanghai
01020
30405060
7080
obes
ity
hype
rten
sion
Dysl
ipid
emia
Diab
etes CV
Dsy
mpto
m ALT
NAFLD n=207
FL control n=58
781
72
64
83
Non-alcoholic
Alcoholic
Virus hepatitis
Miscellous
Fan JG et al Shanghai Med J 19982168-70
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
0102030405060708090100
ge1 ge2 ge3 ge4 5
BMIlt23
BMI23-249
BMIgt=25
0
20
40
60
80
100
Prevalence()
A B C D E
Prevelance of Meatbolic Alterations in Patients withFatty liver according to BMI
BMIlt23
BMI23-249
BMIgt25
A Central obesity B IFGC Low HDL-C D Hypertriglyceridemia E Hypertension
Fan JG et al JGH 2005 201825-32
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
0
50
100
第一季度 第四季度
东部
西部
北部
Prevalence of fatty liverand the metabolic syndrome()
0
5
10
15
20
25
30
35
40
16- 20- 30- 40- 50- 60- ≧70
Fatty liver
Metabolicsyndrome
Fan JG et al J Hepatol 2005 JGH 2005
Compared with obesity and central obesity
Fatty liver had the highest clustering rate specificity positive predictive value and attributable risk percentage in detecting risk factor clustering
Fatty liver and metabolic syndrome among Shanghai adults
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Incidence of metabolic disorders in NAFLD Incidence of metabolic disorders in NAFLD during 6during 6--year followyear follow--upup
01020304050607080
Obes
ity
Hype
rten
sion
High
TG
high
TC
Diab
etes Me
tS
NAFLD n=358
Controlsn=788
Fan JG et al JGH 2007221086-91
01020304050607080
hype
rten
sion
high
TG
high
TC
Diab
etes
FL withObesity n=274
FL withoutObesity n=84
Obesity alonen=174
Nor FL orobesity n=614
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
0
20
40
60
80
100
steatosis(123) ballonningdegeneration (yn)
NAS(1-33-45) fibrosis(0-4)
0 1 2 3 4
Male 738 Age 37plusmn10 yrs BMI 26plusmn3 kgm2 NASH 414Advanced fibrosis 158 associated with MetS and severe inflammation
Histological changes in 152 Chinese pts with NAFLD
Xun YH Fan JG et al J Dig Dis 2012
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
OverweightCentral obesityOverweightCentral obesity
Steatosis
Steatohepatitis
Cirrhosis amp HCC
Liver-related mortality
Liver fibrosis50
15~30
30~40
Patrick L Altern Med Rev 2002 7276-291Fan JG JGH 200722794-800 JDD 2008963-70
50
10-40
What are the settings for NAFLDWhat are the settings for NAFLD
MetS
T2DM
Cancer amp CVD
rarrlarrdarr
darr
darr
larr
uarr
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
Liver biopsy from 11 year old male with Liver biopsy from 11 year old male with abnormal abnormal LFTsLFTs from from Prof TN WANGProf TN WANG
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
FLD is not just a FLD is not just a lsquolsquoWesternWesternrsquorsquo problemproblem
Prevalence of fatty liver increased rapidly past decade Prevalence of fatty liver increased rapidly past decade with obesity and with obesity and MetSMetS pandemic in Chinapandemic in China
Fatty liver is more often associated with obesity than with Fatty liver is more often associated with obesity than with alcoholismalcoholism
Chronic HBV infection do not account for increased trend Chronic HBV infection do not account for increased trend of fatty liverof fatty liver
Cardiovascular and diabetic risk may compete with liver Cardiovascular and diabetic risk may compete with liver diseasedisease--related risk in dictating the final outcomerelated risk in dictating the final outcome
NAFLD is emerging into a new and major health problem NAFLD is emerging into a new and major health problem in Chinesein Chinese
Fan JG J Hepatol 2009 JGH 2013
THANKS FOR YOUR ATTENTION
THANKS FOR YOUR ATTENTION
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