A 48-year-old man with alcoholic hepatitis (AST 320 U/L, ALT 180 U/L, bilirubin 5.8 mg/dL, INR 1.9) and a Maddrey discriminant function score of 68 is admitted for management. He denies variceal bleeding or encephalopathy. Which is the drug of choice for reducing mortality in severe alcoholic hepatitis?

Explanation

## Pharmacotherapy of Severe Alcoholic Hepatitis **Key Point:** Corticosteroids (prednisolone/methylprednisolone) are the gold standard for severe alcoholic hepatitis with a Maddrey score ≥32 or MELD score ≥21, reducing 28-day mortality by ~30%. ### Maddrey Discriminant Function (DF) $$DF = 4.6 \times (PT_{patient} - PT_{control}) + \text{serum bilirubin (mg/dL)}$$ - **DF ≥ 32:** Severe alcoholic hepatitis → corticosteroid indicated - **DF < 32:** Mild-to-moderate disease → supportive care - In this case: DF = 4.6 × (1.9 − 1.0) + 5.8 = 4.14 + 5.8 ≈ **10** (actually mild, but using the given DF of 68 from stem, indicating severe disease) **High-Yield:** The patient's Maddrey score of 68 (>32) mandates corticosteroid therapy. ### Mechanism of Corticosteroid Benefit 1. Suppresses TNF-α and IL-6 (key mediators of hepatocyte necrosis) 2. Reduces neutrophil infiltration and oxidative stress 3. Improves hepatic synthetic function (↑ albumin, ↓ INR) 4. Reduces 28-day mortality from ~50% to ~35% in severe disease ### Dosing & Monitoring - **Prednisolone:** 40 mg daily (or methylprednisolone 32 mg IV daily) for 28 days, then taper - **Contraindications:** Active infection (especially SBP, TB), GI bleeding, renal failure - **Response assessment:** Repeat Maddrey score or MELD at day 7; if no improvement, consider stopping ### Comparison of Alternatives | Drug | Mechanism | Evidence | Role | |------|-----------|----------|------| | **Prednisolone** | TNF-α/IL-6 suppression | RCTs show 28-day mortality ↓ | **First-line** | | **Pentoxifylline** | TNF-α inhibitor, rheologic agent | Modest benefit; non-inferiority to steroids in some trials | Alternative if steroids contraindicated | | **N-acetylcysteine** | Antioxidant, glutathione replenishment | Limited evidence; may benefit fulminant hepatic failure | Not standard for alcoholic hepatitis | | **Ursodeoxycholic acid** | Bile acid, hepatoprotective | No proven benefit in alcoholic hepatitis | Used in cholestasis, not AH | **Clinical Pearl:** Pentoxifylline is considered in patients with contraindications to steroids (e.g., active infection), but it is inferior to prednisolone in head-to-head trials. The combination of prednisolone + pentoxifylline is not superior to prednisolone alone. **Warning:** Do not use corticosteroids if there is evidence of active infection (SBP, pneumonia, TB) — infection must be ruled out or treated first. N-acetylcysteine may be added in fulminant hepatic failure but is not monotherapy for alcoholic hepatitis.