A 48-year-old man with biopsy-proven alcoholic hepatitis (Maddrey discriminant function = 62) is admitted with fever and worsening jaundice despite abstinence. Infection has been excluded. Which drug is the first-line pharmacological treatment for severe alcoholic hepatitis?

Explanation

## First-Line Pharmacotherapy for Severe Alcoholic Hepatitis **Key Point:** Corticosteroids (prednisolone) are the first-line pharmacological agent for severe alcoholic hepatitis, with proven short-term mortality reduction in patients with high Maddrey discriminant function (≥32) or MELD score ≥21. ### Diagnostic Criteria for Severe Alcoholic Hepatitis **Maddrey Discriminant Function (MDF):** $$MDF = 4.6 \times (PT_{patient} - PT_{control}) + \text{serum bilirubin (mg/dL)}$$ - **MDF ≥ 32** = Severe alcoholic hepatitis; mortality ~50% without treatment - **MDF < 32** = Mild to moderate; supportive care alone **Alternative:** MELD score ≥21 also indicates severe disease warranting corticosteroids. ### Prednisolone Regimen - **Dose:** 40 mg daily for 28 days, then taper over 2–4 weeks - **Mechanism:** Reduces hepatic inflammation and TNF-α-mediated injury - **Evidence:** Level 1A; reduces 28-day mortality by ~10–15% in severe disease [cite:Harrison 21e Ch 297] - **Contraindications:** Active infection (must exclude SBP, pneumonia, UTI), GI bleeding, renal failure ### Comparison of Agents in Alcoholic Hepatitis | Agent | Mechanism | Efficacy in Severe AH | Role | |-------|-----------|----------------------|------| | **Prednisolone** | Anti-inflammatory; TNF-α inhibition | ↓ 28-day mortality (1A evidence) | **FIRST-LINE** | | **Pentoxifylline** | TNF-α inhibitor; rheologic agent | Modest benefit; less effective than steroids | Second-line or adjunct | | **N-acetylcysteine** | Antioxidant; glutathione replenishment | Marginal benefit; mainly in combination | Adjunctive only | | **Infliximab** | TNF-α monoclonal antibody | Increased mortality in severe AH | **CONTRAINDICATED** | **High-Yield:** Prednisolone is the only agent with robust Level 1A evidence for mortality reduction in severe alcoholic hepatitis. Infliximab was abandoned after trials showed increased mortality, likely due to increased infection risk. **Warning:** Do NOT give corticosteroids without first excluding active infection (blood cultures, ascitic fluid analysis, chest X-ray, urinalysis). Infection is an absolute contraindication. **Clinical Pearl:** The benefit of corticosteroids is seen primarily in the first 28 days. Long-term abstinence and nutritional support (thiamine, folate, zinc) are equally critical for survival and liver recovery.