alcoholic cirrhosis

**Definition:** Irreversible, diffuse fibrosis with regenerative nodule formation and distortion of hepatic architecture due to chronic alcohol exposure. Classically micronodular (nodules <3 mm), also called Laennec cirrhosis; may become mixed/macronodular over time.

**Stages of alcohol-related liver disease:** 1. Hepatic steatosis (fatty liver): reversible with abstinence; macrovesicular fat; seen in nearly all heavy drinkers. 2. Alcoholic hepatitis: neutrophilic infiltrate, hepatocyte ballooning, **Mallory-Denk bodies** (damaged intermediate keratin filaments, eosinophilic cytoplasmic inclusions), spotty necrosis; fever, tender hepatomegaly, jaundice, leukocytosis. Severe cases assessed by Maddrey discriminant function (≥32) or MELD; treated with corticosteroids. 3. Cirrhosis: irreversible fibrosis; only ~10–20% of heavy drinkers develop it. Risk is higher in women, with genetic factors (PNPLA3), obesity, and coinfection with HCV.

**Pathophysiology:** - Ethanol is metabolized by alcohol dehydrogenase (cytosol) → acetaldehyde, then by aldehyde dehydrogenase (mitochondria) → acetate. Both steps generate NADH, so the NADH/NAD⁺ ratio rises. This shifts pyruvate → lactate (lactic acidosis, hypoglycemia from impaired gluconeogenesis), oxaloacetate → malate, and promotes fatty acid synthesis and decreased β-oxidation (steatosis). - Acetaldehyde is toxic and forms protein adducts. Chronic ethanol also induces CYP2E1 (MEOS), producing reactive oxygen species. Gut-derived endotoxin (LPS) activates Kupffer cells → TNF-α, IL-6, IL-8 → inflammation. - Hepatic stellate cells (Ito cells) activated by TGF-β → collagen deposition → fibrosis (perisinusoidal/pericellular "chicken-wire" fibrosis). - Malnutrition, thiamine/folate deficiency often coexist.

**Clinical features:** - Hepatic synthetic failure: jaundice, coagulopathy (↑PT/INR; factors II, VII, IX, X), hypoalbuminemia (edema, ascites), hyperammonemia → hepatic encephalopathy (asterixis). - Portal hypertension: ascites, splenomegaly/hypersplenism (thrombocytopenia), esophageal varices (hematemesis), caput medusae, hemorrhoids (portosystemic shunts). - Hyperestrogenism (impaired estrogen metabolism): spider angiomata, palmar erythema, gynecomastia, testicular atrophy, loss of body hair. - Other: Dupuytren contracture, parotid enlargement, muscle wasting, macrocytosis, hepatorenal syndrome, hepatopulmonary syndrome, spontaneous bacterial peritonitis, hepatocellular carcinoma.

**Labs:** AST:ALT >2:1 (AST typically <300, ALT often <100 because of pyridoxal phosphate (B6) deficiency and mitochondrial AST injury), ↑GGT, macrocytosis (↑MCV), ↑bilirubin, ↓albumin, ↑INR, thrombocytopenia. Elevated CDT can be used as a marker of heavy use. Serum-ascites albumin gradient (SAAG) ≥1.1 g/dL in ascites from portal hypertension.

**Histology:** Micronodular cirrhosis with fibrous septa, residual steatosis, Mallory-Denk bodies, neutrophilic infiltrates, and cholestasis may be seen. Diagnosis is usually clinical with imaging (nodular liver, ascites, splenomegaly), elastography, or biopsy if uncertain.

**Management:** - **Alcohol abstinence** is the most important intervention (improves survival at any stage). Treat withdrawal (benzodiazepines), and give thiamine, folate, and nutritional support. Relapse prevention: naltrexone (avoid in acute liver failure/severe disease; caution), acamprosate (renally cleared; safe in liver disease), baclofen; disulfiram is hepatotoxic—avoid. - Ascites: sodium restriction, spironolactone ± furosemide, large-volume paracentesis with albumin. - Varices: nonselective β-blockers (propranolol, nadolol, carvedilol) or endoscopic band ligation for prophylaxis; acute bleed: octreotide, IV antibiotics (ceftriaxone), band ligation, ± TIPS. - Encephalopathy: lactulose, rifaximin. - SBP: ascitic PMN >250/mm³; treat with ceftriaxone/cefotaxime and albumin; prophylaxis with a fluoroquinolone/TMP-SMX after an episode. - HCC surveillance: ultrasound ± AFP every 6 months. - Liver transplant for decompensated disease (typically requires a period of abstinence/engagement in treatment, though criteria are evolving for severe alcoholic hepatitis). - Vaccinate against HAV/HBV.

**High-yield associations/buzzwords:** Laennec cirrhosis; micronodular; Mallory-Denk bodies; AST:ALT >2; ↑GGT; macrocytosis; Dupuytren contracture; parotid enlargement; hyperestrogenism; Wernicke-Korsakoff; ↑NADH/NAD⁺ → hypoglycemia, lactic acidosis, fatty liver; complication risk: HCC, varices, hepatorenal syndrome, SBP. Child-Pugh and MELD scores for prognosis.

**Differential for micronodular vs macronodular:** Alcoholic cirrhosis is typically micronodular, whereas viral hepatitis (HBV, HCV) and α1-antitrypsin deficiency tend to cause macronodular cirrhosis. Hemochromatosis is micronodular (bronze diabetes, ↑ferritin, ↑transferrin saturation). Primary biliary cholangitis and PSC cause biliary cirrhosis.