Alcoholic Hepatitis

Alcoholic Liver Disease1. Hepatic Steatosis ( Fatty Liver Disease )

2. Alcoholic Hepatitis

3. Cirrhosis

Hepatic Steatosis• Moderate intake -Microvesicular lipid droplets.• Chronic intake – Macrovesicular globules

• Initially cenrilobular.

• Macroscopy – • Large (4-6kg), soft, yellow & greasy.

• Little or no fibrosis at onset.• Continued intake – around central veins.

• Completely reversible.

Hepatic Steatosis

Alcoholic Hepatitis1. Hepatocyte swelling & necrosis2. Mallory Bodies3. Neutrophil infiltration4. Fibrosis

Mallory Bodies• Tangled skeins of cytokeratin intermediate filaments

(cytokeratin 8 & 18…) & other proteins ( ubiquitin..).

• Eosinophilic cytoplasmic inclusions.

• Primary biliary cirrhosis, Wilson disease, chronic cholestatic syndromes & hepatocellular tumors.

Mallory bodies

1 .High-power view of hepatic macrosteatosis and microsteatosis. The small intracellular fat vacuoles give the hepatocytes a foamy appearance. Note megamitochondria (arrowhead) (hematoxylin-eosin).

2. High-power view of hepatocytes containing Mallory bodies. The chemotaxis of the denatured cytokeratin filaments attracts neutrophils (hematoxylin-eosin).

3. Immunoperoxidase reactivity of Mallory bodies with antibody to low–molecular weight cytokeratin.

4. Immunoperoxidase reactivity of Mallory bodies with antibody to ubiquitin.

Fibrosis

• Brisk sinusoidal & perivenular fibrosis.

• “Creeping collagenosis”

• Periportal fibrosis – repeated bouts of heavy alcohol intake.

• Cholestasis, iron deposits.

• Macroscopic – liver mottled red with bile stained areas.

Alcoholic Hepatitis

Alcoholic Steato -hepatitis

Alcoholic Cirrhosis• First – yellow tan, fatty, enlarged, over 2kg.• Brown shrunken non fatty organ.

• Initial- fibrous septa delicate, extend through sinusoids from C.V to portal regions as well as from portal tract to portal tract.

• Micronodules - < 3cm• Regenerative activity of entrapped parenchymal hepatocytes.

• Scattered larger nodules – “Hobnail Appearance”.

• More fibrotic, loses fat, shrinks progressively.

• Last - Mixed micronodular & macronodular pattern.

• Pale scar tissue – ischemic necrosis, fibrous obliteration of nodules → Laennec cirrhosis.

• Bile stasis often.

• Mallory bodies rare

Alcoholic Cirrhosis

PATHOGENESIS• 50-60g/day

• Women > men• Alcohol pharmacokinetics• Estrogen dependent liver response to gut endotoxin.

• Genetic

• Co morbid conditions – iron overload, infections.

Hepatocellular steatosis1. Shunting of normal substrates away from catabolism and

toward lipid biosynthesis• Excess NADH

2. Impaired assembly & secretion of lipoproteins

3. Increased peripheral catabolism of fat.

Alcoholic Hepatitis1. Acetaldehyde → lipid peroxidation

→ acetaldeyhde-protein adduct formation• Disrupts cytoskeletal & membrane function

2. Directly affects microtubular organisation, mitochondrial function & membrane fluidity.

3. ROS – by Microsomal ethanol oxidising system & neutrophils

4. Alcohol induced impaired hepatic metabolism of methionine → ↓ed glutathione levels.

5. Hypoxia.

• Induction of cytochrome P- 450 → transformation of other drugs to toxic metabolites.

• Abnormal cyokine regulation.• TNF – main effector of injury.• Stimuli for producing cytokines ( IL-6, IL-8, IL-18, TNF) –• ROS & Endotoxins.

• Also alcohol stimulate release of endothelins – decreased hepatic sinusoidal perfusion.

• Centilobular region

CLINICAL FEATURES• Hepatic Steatosis -• Hepatomegaly• Elevation of serum biluribin & ALP.

• Alcoholic Hepatitis –• Malaise, anorexia, tender hepatomegaly,fever• lab findings of hyperbilirubinemia, elevated ALP, neutrophilic

leukocytosis.• Serum AST & ALT elevated, below 500U/ml.• Acute cholestatic syndrome

Alcoholic cirrhosis• Distended abdomen, ascites, wasted extremities, caput

medusa.• Variceal hemorrhage or hepatic encephalopathy.

• c/c alcoholics - malnutrition

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