Alcoholic Hepatitis

Alcoholic Liver Disease

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

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.
• 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