Non-alcoholic fatty liver disease and childhood obesity

Indian Journal of Pediatrics, Volume 74—April, 2007 401

Correspondence and Reprint requests : Dr. Prof. Narendra K. Arora,Division of Pediatric Gastroenterology, Hepatology and Nutrition,Department of Pediatrics, All India Institute of Medical Sciences,New Delhi-110029 India.

Non-Alcoholic Fatty Liver Disease and ChildhoodObesity

Prashant Mathur, Manoja K Das1 and Narendra K Arora2

Indian Council of Medical Research, New Delhi1INCLEN Trust, New Delhi2Department of Pediatrics, AIIMS & Executive Director, INCLEN Trust, New Delhi.

ABSTRACT

Obesity has emerged as a significant global health problem in the pediatric population. Pediatric liver disease is a seriouscomplication of childhood obesity. Non-alcoholic steatohepatitis (NASH) is an entity in the spectrum of non-alcoholic fatty liverdisease (NAFLD) ranges from fat in the liver – simple steatosis, NASH/ steatohepatitis – fat with in.ammation and/or fibrosisto advanced fibrosis and cirrhosis when fat may no longer be present. NASH is associated with obesity, diabetes, insulinresistance (IR), and hypertriglyceridemia. Children get NAFLD, and the incidence of this pediatric liver disease is rising aschildhood obesity becomes increasingly prevalent. Although much remains to be learned about pediatric NAFLD, it is alreadyevident that children with NASH risk progressive liver damage, including cirrhosis. Liver biopsy is required for definitive diagnosis,and other causes of fatty liver in childhood must be excluded. Gradual weight loss through increased regular exercise and a low-fat, low–refined carbohydrate diet appears to be effective. Drug treatments are being developed. The important message is thatchildhood obesity poses important health problems, including but not limited to potentially severe chronic liver disease. Earlydiagnosis of children who are only overweight is a worthy goal so that strategies to limit obesity can be instituted as early aspossible. Identification of genetic risks is important, but management will invariably require changes in environmental factors.In addition to individual treatment, a multifaceted, societal initiative is required for solving the childhood obesity epidemic.[Indian J Pediatr 2007; 74 (4) : 401-407] E-mail: [email protected]

Key words : Childhood obesity; Non-alcoholic fatty liver disease; Epidemiology; Risk factors; Outcome

Obesity has emerged as a global epidemic in childrenwith a spectrum of psycho-social and medicalconsequences manifesting across the lifespan. Adiposityaffects almost all organs of body, but some systems likecardiovascular and endocrine are affected to a greaterextent than others. Obese children are at higher risk forhypertension, hyperlipidemia, arteriosclerosis, anddiabetes mellitus type-2.1 Chronic liver disease associatedwith obesity has been identified in adults as a distinctidentity since 1970s, and after almost a decade thecondition was reported in children and adolescents.Moran et al provided the first report on severe hepatitisand fibrosis associated with obesity in 3 children aged 10-13 years.2

Non-Alcoholic Fatty Liver Disease (NAFLD) describesa spectrum of liver disease in persons who have not

[Received March 3, 2007; Accepted March 19, 2007]

consumed alcohol in significant amounts so as to causeliver damage, and in whom no other etiology for fattyliver is present. The pathological spectrum ranges fromsimple hepatic steatosis, to infiltration by inflammatorycells and mild to moderate fibrosis (Non-alcoholicSteatohepatitis-NAHS) leading to cirrhosis.3 Withadvancing fibrosis, the steatotic component diminishes sothat in cirrhotic livers fat may no longer be seen.Pathologically, NAFLD is a result of complexhepatocellular metabolic dysfunctions in which insulinaction is deranged, leading to deranged metabolism of fatand free fatty acids and subsequent oxidant mediateddamage to the hepatocytes. Several factors sustain andamplify this cytotoxic mechanism. It is not clear whethersimple hepatic steatosis in children is benign or evolves toNASH over time. Usually the abnormality of liver isdiscovered incidentally while evaluating a child for painabdomen or some other unrelated ailment.

Childhood presents a unique period of growth anddevelopment where the causes of fatty liver areenumerable as compared to adults. Broadly, they can bedivided into:

SYMPOSIUM : Gastroenterology & Hepatology

P. Mathur et al

402 Indian Journal of Pediatrics, Volume 74—April, 2007

1. Hepatic Causesa. Overweight and Obesity relatedb. Metabolic liver diseases (wilson disease,

galactosemia, hereditary fructose intolerance,glycogen storage disorders, sialidosis, mannosidosis,fucosidosis, hereditary tyrosinemia, alpha anti-trypsin deficiency, homocystinuria,abetalipoproteinemia, wolman disease, tangiersdisease)

c. Syndromes (Schwachman-Diamond syndrome,Bardet-Biedel syndrome, Alstrom syndrome,Lipodystrophy syndromes, Turners syndrome,Cohen syndrome, Prader-Willi syndrome, Kabuki-Niikawa-Kuroki syndrome, Dorfman-Chanarinsyndrome, Poly Cystic Ovarian Syndrome)

d. Chronic viral hepatitis Ce. Autoimmune hepatitis, sclerosing cholangitis and

others.

2. Non-Hepatic causes

a. Nutritional: prolonged protein calorie malnutrition,total parenteral nutrition, starvation, intestinalbypass surgery, rapid weight loss,

b. Infections: HIVc. Drugs (glucocorticoids, hypervitaminosis-A,

methotrexate, L-asparginase, zidovidune,amiodarone, didanosine, diltiazem), and toxins(mushrooms- Amanita phalloides)

d. Diabetes mellituse. Inflammatory bowel disease, cystic fibrosis, celiac

disease, nephritic syndrome and others.Thus, one has to consider and rule out several

conditions associated with a fatty liver before labeling apatient with Nonalcoholic fatty liver disease (NAFLD).

This article describes the epidemiology of idiopathicchildhood obesity associated liver involvement.

Prevalence of NAFLD in Overweight and ObeseChildren

The exact prevalence of NASH/ NAFLD is not wellestablished. Based on the biopsies of potential donors fortransplant, autopsy studies of accident victims andhospital based studies, about 2-3% of lean and 15-20% ofobese adult individuals have steatohepatitis.4 Amongchildren the information on its prevalence is scanty.Pooling data from studies performed mainly in tertiarymedical centers, the prevalence of NAFLD in obesechildren has been reported to range from 20 to 77%.4

Worldwide studies conducted amongst overweightand obese children and adolescents have shown liverinvolvement in a significant proportion using variousdiagnostic modalities in isolation or combination. In anItalian multicentric study, abnormal serumaminotransferases were documented in 10-25% of obesechildren.5 In same country, 375 obese children aged 9-16years, 42% had steatosis by sonography and presence of

steatosis correlated well with Body Mass Index (BMI).6 InChinese obese children (n=84) studied, 77% had evidenceof hepatic steatosis on sonography. Both sonographicevidence of steatosis and raised ALT levels weredocumented in 24% children, and these children hadhigher waist-hip ratios than those with simple steatosisand, affected males had greater degree of insulinresistance.4 Amongst overweight and obese Germanchildren (n=182) with no evident co-morbidities, serumALT was at high normal or above normal level in 48% ofthem while mean AST and GGT were normal.7 InCanadian children (n=36; 4-16 years) from multiethnicorigin with body weight ranged from 114-192% of idealweight-for-height, liver biopsy (done in 24 children) hadfeatures of some fibrosis in 71% and cirrhosis in one.About 30% of the cohort had acanthosis nigricans, aknown association with insulin resistance.8

Assessment of Obesity Related Liver Involvement inNAFLD

Investigators have used various methods (either singly orin combination) to determine the prevalence of NAFLDin childhood. The presence, degree and pattern ofaminotransferase elevation are non-specific and do notprovide etiological differentiation when used in isolation.Ultrasound of the liver has been found to be a goodscreening tool for assessment of the degree of fat in theliver, but it does not correlate well with the degree offibrosis. Joseph et al9 reported a sensitivity of 89% andspecificity of 93% in detecting steatosis in the liver, and asensitivity of 77% and specificity of 89% in detectingincreased fibrosis in the liver. The sensitivity of CT scansvaried from 54% to 93% and specificity between 87% to97%, depending on the protocol followed.10 Fishbein et al11

evaluated 22 obese (BMI>95th percentile) children withhepatomegaly by estimating their hepatic fat fraction (FF)by a modified Dixon method using fast MRI scanning,and have reported a sensitivity of 92% and specificity of100% in detecting NAFLD when combined with serumALT estimation. Ultrasound screening for presence offatty liver in high risk individuals seems to be areasonable tool, while CT scans and MRI are very costlyand not feasible at the moment for use in routine work upof suspected NAFLD. Liver biopsy remains the goldstandard for diagnosis of steatosis and various degrees offibrosis, and for comparison of various other diagnosticmodalities.

A. Elevated Serum Aminotransferases

Studies have estimated alanine aminotransferases (ALT)and aspartate aminotransferases (AST), either in isolationor in combination to estimate the prevalence of fatty liverin childhood. In NAFLD the ALT and AST levels areelevated to up to 5 times the upper limit of normal. Theratio of ALT: AST in obese individuals is reported to begreater than 1. The proportion of obese children with

Non-Alcoholic Fatty Liver Disease and Childhood Obesity


elevated serum aminotransferases is summarized in thefigure below respectively.12, 8, 13, 14-17, 11, 18.

The largest community based pediatric data onNAFLD from US was provided by Strauss et al12 in 2000,where they estimated obesity and overweight in 2450children aged 12 to 18 years of age who were surveyedduring the NHANES III (1988-1994), and estimatedserum aminotransferases in 86% of the sample. Theoverall prevalence of overweight and obese children was16% (BMI between 85th and 95th percentile) and 10% (>95th percentile) respectively. Serum ALT was raised aboveh

30IU/L in 75 children, and of them 61% were obese. Theprevalence of raised ALT levels was significantly higherin overweight (5%) and obese children (9.5%)respectively, as compared to normal weight children(1.5%). The odds of raised ALT levels in overweight andobese children as compared to normal weight childrenwas 3.4 (95% CI 1.7- 6.8) and 6.7 (95% CI 3.5- 12.8). In thisstudy GGTP levels were also significantly raised inoverweight (1.3%) and obese (3.9%) children.

Several studies from various regions of Japan havereported varying proportions of children with elevatedliver enzymes in obese children (9.5% to 32%).19, 20, 21

Kawasaki et al17 used ALT as the predictor of fatty liver in7

228 obese children and found the correlation with degreeof obesity to be the third best (r= 0.262; p<0.001) ascompared to immunoreactive insulin and serumtriglycerides. They were able to demonstrate high ALT(24.1%), AST (11%) and cholinesterase (54.8%) amongst1.3%, 49.1% and 49.6% children with mild, moderate andsevere obesity respectively. A formidable association ofchildhood NASH with obesity (%IBW) was found in astudy in 30 obese children in Toronto.8 Theaminotransferases were raised above the normal in 35 outof 36 children (mean ALT 179 ± 31U/L; AST 104 ±16 U/L). Follow up of 75 obese children (age range 4.5- 15.9years) revealed hypertransaminasemia in 18 (24%) ofthem.15 Of these children, 10 (56%) children had high ALTand AST levels, 5 (28%) had only elevated ALT and 3(17%) had only AST elevation. The enzymes were raised1.1 to 2.9 times the upper normal limit. There was no

correlation between the levels of transaminase levels andthe age or degree of obesity of the children. Aretrospective analysis of liver biopsies identifiedidiopathic steatohepatitis in 14 (22%) children out 650liver biopsies screened. The ALT and AST levels wereelevated at the time of diagnosis in some of thesechildren.22

B. Fatty Liver on Imaging

Ultrasonography, CT and MRI scanning are reliable fordetecting moderate to severe fatty changes in the liver.Hepatic fat gives hyperechogenic feature on ultrasoundcompared to spleen, while it gives hypodense shadowson CT scan. Sonologically accurate diagnosis can be madewhen there is moderate or severe (>33%) fatty infiltrationof liver and radiological modalities may not be able todetect or characterize NASH and differentiate it fromsteatosis alone.23 MRI is the only noninvasive modalitywith ability to quantify the fat content of liver.

No imaging method is able to distinguish betweensimple steatosis and NASH and/or indicate the stage offibrosis. Ultrasonography has a sensitivity of 82 to 90%for detecting a fatty liver, and the sensitivity approaches100% when steatosis involves more than 10% of the liveron biopsy. When it shows an echogenic pattern of theliver, its specificity for detecting steatosis is 93%.24, 25

Though fibrosis and inflammation may result in a typicalultrasonographic pattern, this finding does not reliablydistinguish fat from fibrosis or reliably diagnose cirrhosis.Hepatic inflammation, fibrosis and cirrhosis are mostaccurately diagnosed by liver biopsy results. Routine CTscanning does not add more information on fatty liverdisease that what is known from ultrasonography.

Studies have shown that ultrasonography has a lowsensitivity (80% and 88.6%) in measuring the degree ofsteatosis in the liver and that this is confirmed by itsinability to discriminate hepatic fibrosis from steatosis.Using hepatic MRI with the Dixon method to estimate thehepatic fat fraction (FF), and diagnosed fatty liver if thehepatic FF was > 19%, the hepatic FF was elevated in 95%(21 out of 22) children, and those with hepatic FF greaterthan 18% (n-13, 59%) had elevated serum ALT also.11 Thisstudy identified children into two groups: those withhepatic FF ≤18% and normal ALT/AST and, those with≤≤hepatic FF > 18% and high aminotransferases. It appearsthat beyond 18% hepatic FF, ALT abnormalities rise and,these children may progress to develop NASH. Therewere 9(41%) children with hepatic FF between 8-19% and13 (59%) had ≥ 20%. Thus, a large proportion of obesechildren may be missed at screening based only on serumaminotransferases. In a study in 75 obese Italianchildren,15 fatty liver was present in 38(53%) children asevidenced by ultrasound. It was severe in 9, moderate in16 and mild in 13 patients. The mean IBW% wassignificantly higher in those with fatty liver on USG thanin others (p< 0.001). Elevated serum aminotransferases

Fig. 1. Proportion of Obese Children with Elevated SerumAminotransferases

Aminotransferases

P. Mathur et al


were present in 12 (17%) children whose USG had shownfatty liver, while in 26 children they were normal. ThusUSG was also able to detect more children with fatty liverthan aminotransferases alone. In the largestepidemiological study on fatty liver in obese childrenusing USG, Tominaga et al19 found the prevalence of fattyliver in 2.6% amongst 810 children aged 4-12 years oldattending a public kindergarten and elementary school inNorthern Japan. The study found a direct relationshipbetween the degree of obesity and the prevalence of fattyliver, subcutaneous fat estimation by USG as a betterpredictor of fatty liver than Rohrer’s index, BMI and JSI.

C. Histopathological Evidence of NAFLD

No single microscopic finding is diagnostic of NASH. Atpresent liver histopathology is the gold standard forNAFLD clinicopathologic correlation and exclusion ofother causes. In adults, histological features of NAFLDhave been well-described and include microvesicularsteatosis, perisinusoidal, or pericellular fibrosis, foci oflobular inflammation, lipid granulomas, Mallory hyalineand megamitochandria.26 The entire histopathologicalspectrum of NAFLD has been described in children aswell: steatosis, steatohepatitis, fibrosis, and cirrhosis. Themajor pitfall in the available literature is the smallersample size and/or non uniform reporting ofhistopathology reports.

In a review of 650 liver biopsies of children withchronic liver disease for the presence of NAFLD, microand macrovesicular fatty change was present in 82(12.6%) of these biopsies, suggesting fatty liver.22

However, in 68 (83%) biopsies other etiologies of liverdisease could be established and in 14(17%) cases, theetiology of fatty liver was not found. Thus, overall 2.1%(14/650) biopsies were correlated to NAFLD, since allthese 14 children were obese (body weight- 121-222% ofideal body weight) and ultrasound showed fatty liver.The aminotransferases were elevated in 12 (86%)children, above the normal values.

Schwimmer et al27 studied liver biopsy in 100 children7

with a diagnosis of NAFLD. Majority of children (92%)were obese, 6% were overweight. The amount of steatosisranged from 5-100% (mean 64 ± 28% steatotichepatocytes). More than half (53%) children had severesteatosis while 28% had moderate and 19% had mildsteatosis. Lipogranulma (83%), and glycogenated nucleus(55%) were documented is most of children. Portalinflammation (70%) and fibrosis (60%) was documentedin most of the patients overall features like adult NASH(types ) was documented in 17% of children while 51%had a district pattern of NASH (type-2) and in theremaining case, a overlap of both the types was seen. In16% of cases histopathology did not meet the criteria forsimple steatosis. It was clearly documented thathistopathological features of NASH in children are

different from adult NASH with absence of ballooningfibrosis.

Xanthokos et al28 studied the histological spectrum of41 obese American adolescents (13-19yr), and found that83% had NAFLD; 24% had steatosis alone, 7% isolatedfibrosis with steatosis, 32% nonspecific inflammation andsteatosis and 20% NASH. The parameters statisticallyassociated with NASH were higher mean ALT (P=0.05),AST (P=0.01) imitates glucose (P=0.05), but prevalence ofmetabolic syndrome was not statistically different.

Risk Factors and Predictors for Obesity Related LiverInvolvement (NAFLD)

The occurrence of fatty liver has been described fromearly childhood and it increases with advancing age.Overweight and obese children older than 16 years weresignificantly likely to have abnormal ALT levels.12 Withadvancing age the sequelae of hepatic steatosis becomesmore apparent; steatosis, steatohepatitis, cirrhosis, livercancer. Schwimmer et al29 studied the clinical, laboratoryand histopathological parameters of 43 children, between2-17 yrs, with suspected NAFLD. Obesity (BMI based)was present in 88% children, fasting hyperinsulinemiawas present in 75% and insulin resistance (assessed byeither HOMA-IR or QUICKI methods) was present in95% of the subjects. Using multivariate modeling method,hepatic steatosis was significantly (p> 0.0001) predictedby a combination of quantitative insulin sensitivity checkindex, age and ethnicity; portal inflammation waspredicted by combination of elevated ALT and fastinginsulin (p=0.0009); perisinusoidal fibrosis was predictedby a combination of elevated ALT, fasting insulin andBMI Z score (p> 0.0001); and portal fibrosis was predictedby a combinations of right upper quadrant pain andhomeostasis model assessment of insulin resistance(p=0.0028). Thus, children with NAFLD should bescreened for insulin resistance which is nearly universal,and correlates well with liver histology. Rashid et al8 havereported the largest series of 36 children with nonalcoholic steatohepatitis (NASH), and did not find anystatistically significant difference for the mean age, degreeof obesity, and mean ALT and AST levels in childrenwith no fibrosis or severe fibrosis. Franzese et al15 found5

that the age at diagnosis of obesity was significantly moreadvanced in patients with shorter duration of obesity(p<0.0002).

Previously NAFLD was being described in femaleadults, since it was thought that its part of the metabolicsyndrome. However recent reports on pediatric NAFLDhave demonstrated higher prevalence amongst males.

Body fat distribution varies by race and ethnicity. In amultivariate analysis,29 ethnicity was a significantpredictor of macrovesicular fat (p<0.0001), along withQUICKI and age. It was shorter in patients in whom bothUSG liver involvement and increased ALTs. Increased



incidence of USG with fatty liver was seen in subjectswith < 3 yrs duration of obesity than in > 3 yrs (p< 0.005).Franzese et al15 found that children with USGinvolvement (with or without elevated transaminases)had high % IBW values, while Vajro et al16 could notdemonstrate such a relation. NASH may be more severein children from certain ethnic groups, includingHispanics and Asians or in association with somemetabolic disorders involving insulin receptor disorder.

There is increasing evidence that oxidative stresstriggers the excessive deposition of fat in the liver and itssequelae. Strauss et al12 estimated antioxidant levels in4771 (out of 6139) children from the NHANES III study,of which 726 were obese. Irrespective of age and gender,antioxidant levels were significantly lower in obesechildren.

Management of NAFLD

At present there is no consensus for the treatment ofNASH, especially in childhood. But effort needs to bemade to prevent development and progression of fibrosis.As the pathogenesis is unclear, management has beenlargely empirical. Drugs have been targeted at theNAFLD associated conditions like obesity, insulinresistance and diabetes, hyperlipidemia. Prognosis ofNAFLD is dependent on the histologic severity andassociated risk factors.

The key principles of NASH management is weightreduction and hepatocyte protection. Studies have shownnormalization of serum aminotransferases and steatosiswith weight reduction. For adults, a 5-10% weight loss isthought to be adequate for noticeable improvement, butsimilar figure for children is not known. Dietarymodification, changes in lifestyle with increasing physicalactivity are the key for this effort. Family basedinterventions are most effective for its sustenance in longrun. Ursodeoxycholic acid, N-acetylcystine, Betaine havealso been used with some positive outcomes. Metformin,has been shown to reverse fatty liver in obese adults,adolescents with type-2 diabetes mellitus.30

A strong association exists between the presence ofsteatosis in a donor liver and poor graft function, and asa result cadaveric donor livers with macrovesicularsteatosis >40% are not used routinely.30 Assessment ofsteatosis is always a necessary component of donor liverevaluation and prospective liver donors who are at riskshould undergo liver biopsy even if the imaging studiesare normal. Transplantation in the patients of NASHmay be complicated by associated co-morbidities likeobesity, diabetes and hyperlipidemia. At presenttransplantation for overt NASH is rare, but it is possiblethat its contribution may have been underestimated inpast and will most likely rise in the view of increasingobesity prevalence. After development of cirrhosis fromNASH, the histological features of steatosis and various

necroinflammatory changes may become less evident ordisappear.

Outcome of Obesity Related Liver Disease

Simple steatosis is considered as a benign condition withlittle evidence of progression to more severe liver disease,while those with features of steatohepatitis or moreadvanced fibrosis have the worst prognosis. In a series offive studies on NAFLD3, 54 of 257 patients underwentliver biopsy and follow up for 3.5 to 11 years. There were28% with progression of disease, 59% had no change and13% had improvement or resolution of the liver damage.Approximately 30% of obese adults with elevatedaminotransferase levels demonstrated steatohepatitiswith fibrosis or cirrhosis on liver biopsy. Similar data isnot available in children with NAFLD. Children withNAFLD may be at increased risk for cirrhosis if obesity isnot reversed and other factors, such as alcoholconsumption are not avoided. Weight loss will reverseelevations in aminotransferases and reduce hepaticsteatosis, and it may decrease fibrosis.15 In a small series5

of pediatric patients with elevated aminotransferases andfatty liver on ultrasound, those who lost at least 10% oftheir excess weight had normalized their ALT and ASTvalues and decreased ultrasound evidence of fattyinfiltration at the end of 30 months follow up.16 Two outof seven patients who did not comply with the diet andweight reduction regimen, continued to gain weight andhad persisting abnormal liver histology enzymes.Interestingly, three patients tended to regain weightwithout elevation of aminotransferases or ultrasoundabnormalities. In contrast, there was an increase in liverechogenecity with normal liver enzymes in a child whohad normalized aminotransferases and ultrasound, butthereafter had regained weight.15 Thus, the factorsinfluencing recurrence of steatosis are not known.Tazawa et al14 intervened in 73 obese children withdietary and weight reduction programs, and found thatthe changing rates of serum AST/ALT percentage withreturn to normal levels of AST/ALT and frequency ofnormalization or improvement in serum transaminaseswere significantly correlated to the grades of weightreduction (p<0.01).The authors suggest that a weight lossof at least 5% is accompanied with liver histologyimprovement. When liver biopsies were performed inadults after weight loss, all had reduced steatosis, butonly 50% had a reduction in fibrosis. Rapid weight lossmay actually increase fibrosis because of an increase offree fatty acids to the liver and increased lipidperoxidation with resultant increased oxidative stress.This led to the conclusion that rapid weight loss shouldbe avoided in these patients. Lavine etal31 treated obesechildren with daily doses of 400 and 800 IU of a-tocopherol, and demonstrated improvement in serumaminotransferases and hepatic fibrosis within 1 month oftherapy, but increased liver echogenecity persisted.Patients with NASH who develop cirrhosis may require

P. Mathur et al


liver transplantation. But, several case reports haveshown recurrence of steatosis, steatohepatitis andcirrhosis in post-transplant patients.32

The progression and natural history of NAFLD hasbeen shown to vary according to the histological type.Identification of cirrhosis in obese children suggestsprogression of NAFLD to cirrhosis. Probably it alsodepends on the associated body fat related co-morbidities.

Public Health Significance of Obesity Related LiverInvolvement in Children

Its importance from a public health view lies from the factthat its incidence and prevalence is likely to increase withthe growing epidemic of childhood obesity. Theredeeming point is that it can be prevented and treatedthrough life style and behavior modifications. In the US itis estimated that 12 to 24 percent of children are obese(BMI >95th percentile), of these 10 to 25% have elevatedserum aminotransferases. This means that 1 to 4% of allchildren in the US are obese with elevated liver enzymes,and at risk of NAFLD. This adds to the burden of chronicliver diseases due to several other causes. Thus, allcountries could estimate and predict the burden ofNAFLD and galvanize its health resources accordingly.

CONCLUSION

The rise in the number of children who are overweightand obese is becoming a global phenomenon, and eventhe developing countries are experiencing the doubleburden of disease. The most important factors for this areincreased consumption of high fat and sugar containingfood and lack of physical activity. Non-alcoholic fattyliver associated with obesity is now well recognized inchildren as a major cause of chronic liver disease, and hasbeen documented at younger age. The condition ispotentially reversible and preventable. If unchecked, it islikely to progress to steatohepatitis and cirrhosis.Understanding the role the liver plays in the develop-ment and expression of the metabolic program willprovide important insight into the pathogenesis andtreatment of this increasingly common disease.

There is an urgent need to undertake large populationbased studies in children (from pre-school age tilladolescents) from various ethnic and regional areas, todocument the epidemic of obesity using valid andinternationally comparable definitions and measuringtechniques. Trends of the changes will provide healthmanagers and policy makers the recipe for interventions.

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The Indian Journal of PediatricsAWARD FOR BEST ORIGINAL RESEARCH THESIS IN

PEDIATRICS IN INDIA–2006

The Indian Journal of Pediatrics announces Four awards for the year2006 for original research work. The awards will be for the best MDthesis submitted to their Institute/University and accepted during 2006.

The selected awardees will be presented with a citation, Rs 7,000,Rs 5,000, Rs 4,000 and Rs 3,000 for first, second, third and fourthpositions respectively for outstanding research.

Send the objective, materials, methods, relevant results and conclusionsof the thesis for award consideration. There should be a one pagesummary stating why the thesis deserves award. Also send a certificateby the Head of the Department stating that the work is of the candidateand that the thesis has been accepted by the Institute/University.

Matter must not exceed more than 15 pages.

Last date of submission of thesis : June 30, 2007

(Note : If selected, it is essential to publish the article in the journal)

For further information please write to :

Editor-in-ChiefThe Indian Journal of Pediatrics

125 (2nd Floor), Gautam Nagar, New Delhi-110049Post Box No. 3875, New Delhi-110049

Ph: 26857587, 26568098; Telefax : 91-11-26857587E-mail : [email protected], [email protected]

Website: www.ijppediatricsindia.org

Documents

Non-alcoholic fatty liver disease and childhood obesity