Fatty Liver - Handout

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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Fatty Liver - Handout

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