Alcohol-associated liver disease

Epidemiology

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Etiology

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Pathophysiology

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• Metabolic Imbalance: Metabolism by Alcohol Dehydrogenase (cytosol) and Acetaldehyde Dehydrogenase (mitochondria) ↑ NADH/NAD+ ratio.
• Consequences of ↑ NADH: ↓ gluconeogenesis (hypoglycemia), ↓ TCA cycle, ↑ fatty acid synthesis (lipogenesis) $\to$ Steatosis.
• Toxicity: Accumulation of Acetaldehyde causes direct hepatocyte damage and lipid peroxidation.
• Inflammation: CYP2E1 induction $\to$ ROS generation. Upregulation of TNF-$\alpha$ and IL-6.
• Fibrosis: Stellate cell activation (via cytokines/acetaldehyde) lays down collagen in Space of Disse.

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Spectrum & Clinical Features

1. Alcoholic Steatosis (Fatty Liver):
   • Often asymptomatic.
   • Reversible with cessation.
   • Hepatomegaly.
2. Alcoholic Hepatitis:
   • Fever, RUQ pain, jaundice, tender hepatomegaly.
   • May present with “bruit” over liver (rare).
3. Alcoholic Cirrhosis:
   • End-stage fibrosis.
   • Signs of portal HTN: Ascites, caput medusae, splenomegaly, esophageal varices.
   • Signs of liver failure: Asterixis, hepatic encephalopathy, coagulopathy.
   • Stigmata: Spider angiomas, palmar erythema, gynecomastia, testicular atrophy (hyperestrogenism).

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Diagnostics

• Macrovesicular Steatosis: Hepatocytes filled with fat droplets displacing nucleus.
• Ballooning Degeneration: Hepatocyte swelling/necrosis.
• Mallory-Denk Bodies: Intracytoplasmic eosinophilic inclusions composed of damaged cytokeratin intermediate filaments.
• Neutrophilic Infiltrate: Characteristic of acute alcoholic hepatitis.
• Micronodular Cirrhosis: Small nodules (< 3mm) surrounded by fibrous bands (“hobnail” appearance).

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Treatment

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