1. Alcoholic hepatitis is characterized by hepatocyte swelling and necrosis, Mallory bodies, neutrophil infiltration and fibrosis. Mallory bodies are tangled skeins of cytokeratin intermediate filaments that appear as eosinophilic cytoplasmic inclusions. 2. Alcohol metabolism leads to lipid peroxidation, acetaldehyde-protein adduct formation and reactive oxygen species production, impairing hepatic function. Cytokines such as TNF are the main mediators of alcoholic liver injury. 3. Clinical features of alcoholic hepatitis include malaise, anorexia, tender hepatomegaly, fever, hyperbilirubinemia and elevated liver enzymes. Later stages develop complications like ascites, variceal bleeding and

1. Alcoholic Hepatitis

2. Alcoholic Liver Disease
1. Hepatic Steatosis ( Fatty Liver Disease )
2. Alcoholic Hepatitis
3. Cirrhosis

4. 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.

5. Hepatic Steatosis

6. Alcoholic Hepatitis
1. Hepatocyte swelling & necrosis
2. Mallory Bodies
3. Neutrophil infiltration
4. Fibrosis

7. 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.

8. Mallory bodies

9. 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.

10. 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.

11. Alcoholic Hepatitis

12. Alcoholic Steato -hepatitis

14. 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.

15. • 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

19. Alcoholic Cirrhosis

20. PATHOGENESIS
• 50-60g/day
• Women > men
• Alcohol pharmacokinetics
• Estrogen dependent liver response to gut endotoxin.
• Genetic
• Co morbid conditions – iron overload, infections.

21. Hepatocellular steatosis
1. 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.

22. Alcoholic Hepatitis
1. 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.

23. • 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

26. 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

27. Alcoholic cirrhosis
• Distended abdomen, ascites, wasted extremities, caput
medusa.
• Variceal hemorrhage or hepatic encephalopathy.
• c/c alcoholics - malnutrition