Alcoholic hepatitis a Pathology topic for MBBS

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