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.