A 38-year-old man with chronic alcohol use disorder presents with jaundice, hepatomegaly, and elevated transaminases (AST 180 U/L, ALT 95 U/L). Liver biopsy shows hepatocyte ballooning, Mallory-Denk bodies, and neutrophilic infiltration consistent with alcoholic hepatitis. Which drug is the first-line treatment to prevent progression to irreversible cirrhosis?

## First-Line Pharmacotherapy in Alcoholic Hepatitis **Key Point:** Prednisolone (or methylprednisolone) is the gold-standard first-line agent for moderate-to-severe alcoholic hepatitis, as it reduces hepatic inflammation and prevents progression from reversible to irreversible injury. ### Mechanism of Benefit Prednisolone suppresses the hepatic inflammatory cascade (TNF-α, IL-6, IL-8) that drives hepatocyte necrosis and fibrosis in acute alcoholic hepatitis. It halts the transition from reversible hepatocyte injury (ballooning, steatosis) to irreversible cirrhosis. ### Indications & Dosing - **Indication:** Severe alcoholic hepatitis (Maddrey discriminant function ≥32 or MELD score ≥21) - **Dose:** Prednisolone 40 mg daily × 28 days, then taper over 2–4 weeks - **Efficacy:** Improves 28-day and 90-day survival in severe disease ### Role of Other Agents | Agent | Role | Limitation | |-------|------|------------| | N-acetylcysteine | Adjunct in severe cases; synergistic with prednisolone | Not monotherapy; limited evidence as sole agent | | Pentoxifylline | Alternative if contraindication to steroids (e.g., active infection) | Inferior to prednisolone; second-line only | | Ursodeoxycholic acid | Used in PBC/PSC, not alcoholic hepatitis | No role in reversible alcoholic injury | **High-Yield:** Prednisolone is contraindicated if active infection (SBP, pneumonia, TB) is present; in such cases, pentoxifylline or supportive care is preferred. **Clinical Pearl:** The goal is to halt the reversible phase (hepatocyte ballooning, steatosis, inflammation) before it progresses to irreversible fibrosis and cirrhosis. Early intervention with prednisolone within 7 days of symptom onset yields best outcomes. **Tip:** Remember the Maddrey discriminant function: `$DF = 4.6 × (PT – control PT) + serum bilirubin (mg/dL)$`. DF ≥32 = severe; treat with prednisolone.