Corticosteroid therapy of alcoholic hepatitis: How many studies will it take?



Study Objective: To determine the efficacy of a corticosteroid in reducing the short-term mortality of patients with 8evere alcoholic hepatitis.

Design: Randomized, double-blind, placebo-controlled multicenter trial.

Setting: Four university teaching hospitals.

Patients: We enrolled 66 patients with alcoholic hepatitis and either spontaneous hepatic encephalopathy or a discriminant function value greater than 32, calculated using the formula: 4.6(prothrombin time -control time) + serum bilirubin [in pmoUL]/17.1. Fifty-nine patients (89%)completed the study. Two patients withdrew from the trial. The other 64 patients were hospitalized for the duration of the trial: however, treatment was discontinued in 5 patients because of potential drug toxicity.

Interventions: Patients were randomly assigned to receive either methylprednisolone (32 mg) or placebo within 7 days of admission. Treatment was given for 28 days. The doses were then tapered over 2 weeks and discontinued.

Measurements and Main Results: The endpoint of the study was death. Of the 31 recipients of placebo, 11 (35%)died within 28 days of randomization compared with 2 (6%)of the 36 patients given methylprednisolone (p = 0.006). The 95% CI for the difference in mortality was 12% to 70%. In the patients with spontaneous hepatic encephalopathy at entry, 9 of 19 recipients of placebo died (47%)compared with 1 (7%)of the 14 patients given methylprednisolone (p = 0.02). The 95% CI for the difference in mortality was 14% to 66%. The Cox proportional hazards regression model showed the advantage of methylprednisolone over placebo after adjustment for other potentidy important prognostic variables (p = 0.004).

Conclusions: Methylprednisolone therapy decreases short-term mortality in patients with severe alcoholic hepatitis manifested either by spontaneous hepatic encephalopathy or a markedly elevated discriminant function value.