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?
A. Ursodeoxycholic acid
B. N-acetylcysteine
C. Pentoxifylline
D. Prednisolone
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%.
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-YieldNEET PG
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
Table
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.
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