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8/13/2019 Fatty Liver - Handout
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FATTY LIVER
Dr. Suhaemi, SpPD,finasim
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hat a real liver looks like
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Fatty liver Normal liver
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The Normal attenuation of the liver parenchyma
Normal: Liver texture=homogeneousAssessment of its size , configuration, homogeneity ,and contour
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increased sound attenuation=poor definition of posterioraspect of liver ( bright liver)
Fatty Infiltration
impaired visualization ofborders of hepatic vessels
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A. Demonstrates a heterogeneous-appearing echotexture
bright liver
B. Relatively hypodense liver compared to the spleen
(liver-to-spleen ratio
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Diffuse Fatty InfiltrationCT
Areas of lower attenuation than normal portalvein/IVC density
Hyperdense intrahepatic vessels
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Fatty Liver Disease - Definition
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A clinico-pathologic syndrome encompassing a wide
range of fatty liver disease in the absenceof
significant alcohol intake and other common causes of
Steatosis.
The following are the stages.
Non Alcoholic Fatty Liver DiseaseNAFLDNon Alcoholic Steato HepatitisNASH
Non Alcoholic Cirrhosis (> 60% of cryptogenic)
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Adipocyte is an Endocrine Organ
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The Two HIT Concept
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Lipid Accumulation
Oxidative Stress
Cytokine Activation
1st HIT
2nd HIT
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The Two Hit Concept
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Fatty Liver
1stHit
Damaged Liver
2ndHit
Oxidative Stress
Toxins
Inflammatory
Molecules
Susceptibility
Donnelly et al. J. Clin. Invest. 113: 1343, 2005; Day and James. Gastroenterol. 114: 842, 1998
DietFFA
Fats BurntVLDL-TG
Saturated >
Unsaturated
Apoptosis
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These are a Continuum
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Normal
NAFLD
NASH
Cirrhosis
CVRisk
FAT >5% Inflammation
Scarring DCLD
IR and MS
1stHIT 2nd HIT
IR and MS
NAFLD Hi t l i l
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NAFLDHistological
Spectrum
Macrovesicular Steatosis
Lobular Inflammation
Fibrosis
Cirrhosis
T
imeProgres
sion
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Natural History of Fatty Liver
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Severe NASH with fibrosis 75% go in for cirrhosis
5 yr survival 67% 10 yr survival 45%
NASH Ballooning, Inflammation, FibrosisWorse prognosis 30% develop cirrhosis
Simple Steatosis or Fat Deposition of > 5%
Benign course 3% develop cirrhosis
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NAFLDPathogenesis
TRIGLYCERIDE ACCUMULATION
INSULIN RESISTANCE
Lipid Peroxidation and Hepatic Lipotoxicity
Cytokine Activation and Fibrosis
Adiponectin and Leptin (Adipocytokines)
Abnormal Lipoprotein Metabolism
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The New Definition of MS
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Waist Circum 90 (M), 80 (F)
Triglycerides >150 mg
HDL 100 or DM
Hypertension >130 or 85
Rx. for any of the above conditions
2 of 5
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Each Perpetuating the Other
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NAFLD IR
MSDM
NAFLD is the Hepatic
component of MS
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What is the implication
NAFLDNASH
DM, MS,CVD
NASH
IR
98%
MS85%
DM70%
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These are ONE If we find one
look for the other
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IR Adiponectin Obesity,PPAR-
PC, KC, SC,
LEC
CC P450 A,E1
Glutathione
PPAR- ,
SREBP1a,1c,2
NASH, CV Risk
Free radicals
Antioxidants
Kuffer Cells
NF-B
O2 stress,
Inflmma.
Leptin,
IL-6FFA, PC1
Rad, TNF-NEFAs NO
TNF-ATP
in oxidativestress
in oxidation
in DAG & TAG
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The Risk Factors
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What Causes Fatty Liver ?
Alcohol
Obesity, WC
T2DM Triglycerides
Medicines*, TPN
Wilsonss Disease
-1 Anti-trypsin
AI Hepatitis Hepatitis C
Inherited syndromes
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*MTX, VA, Acetaminophen, TC, Tamoxifen,Nefidepine, Amiodarone, CCl4
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NAFLDRisk Factors
Acquired Metabolic Disorders
in 38%
*Obesity*
*Diabetes Mellitus*
*Hypertriglyceridemia*
Total Parenteral Nutrition ,Rapid
weight loss, Acute starvation
SurgeryJejunoileal Bypass
Extensive Small Bowel Loss
Medications
Corticosteroids; Estrogens
Amiodarone
Methotrexate; Tamoxifen
Diltiazem; Nifedipine
Occupational Exposures
Others
Organic Solvents
Wilson's dis,Abetalipoproteinemia
Jejunal diverticulosis
Obesity
Diabetes
MellitusHypertriglyceridemi
a
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Clinical Presentation
Asymptomatic
Routine blood
tests
Liver enzymes
Enlarged Liver
(1/3)
RUQ periumb.
Pain
Fatigue. Malaise
Anorexia, Nausea
> 90% are obese
USG e/o fatty liver Acanthosis
Nigricans
DM, HTN, Lipidabn.
OSAS, Snoring
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Laboratory Abnormalities
2 - 4 fold GPT &GOT
SGOT: SGPT Ratio
< 1
AKP slight in 1/3
Dyslipidemia - TG
FBG and PPBG BUN & Creatinine -
N
Normal Albumin. PT
Low ANA + < 1 in320
Serum Ferritin
Iron saturation
SGOT: SGPT Ratio
> 1if Cirrhosis sets in
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H T ?
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Insulin
resistance
Fatty acids
Steatosis
Lipid
peroxidation
NASH
CytoprotectantsInsulin Sensitizers
Antihyperlipidemics
First HitSecond
Hit
Weight Loss
Diet/Exercise
Antioxidants
How to Treat?
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Potential Drugs for NAFLD
Insulin Sensitizing
Agents
Glitazones;
Metformin
Lipid-Lowering Agents
Clofibrate;
Gemfibrozil
Future Potential
Treatments
Anti-fibrotics;
Membrane-Stabilizing
Urso deoxy cholic
Acid
Betaine (SAM)
Anti-Oxidants
Vitamin E; Vitamin
C
Lecithin; -
Carotene
Vitamin B Com lex26
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Urso deoxy cholic Acid - UDCA
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Evidence of efficacy in NASH/NAFLD is
equivocal
300 mg bid or 10 mg/kg in two divided doses PO
Given up to 12 to 24 months - depends onresponse
Cholestasis, PBC, PSC, Acute viral hepatitis,
HBV, HCV Chronic hepatitis, Alcoholic liver disease
Dissolution of cholesterol microliths / gallstones
Class E drug in pregnancy (not to be used in
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There is No Effective Drug Rx.
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NAFLD and NASH may resolve with weight loss
Liver fat content ; No effect on fibrosis &
Inflam.
Diet and exercise improve insulin sensitivity,
increase oxidative capacity and utilization of
FFAs
Weight loss has clear benefits for CV risk &
T2DM
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Take Home Points
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It is the main cause of liver enzymes; Isnt thatbenign
Spectrum of diseaseNAFLDNASHCirrhosis -
HCC
Insulin resistance, MS are the key pathogenic
features
DM, TG, Non fatty abdominal obesity, increasing
age
Always look for DM, TG, CVD if you see fatty liver
Presently, the management is to improve IR, TG,
DM
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