Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial.
OBJECTIVE
To determine the efficacy of a corticosteroid in reducing the short-term mortality of patients with severe alcoholic hepatitis.


METHODS
Randomized, double-blind, placebo-controlled multicenter trial.


METHODS
Four university teaching hospitals.


METHODS
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 mumol/L]/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.


METHODS
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.


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 35 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 potentially 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.
Carithers
R L
RL
Medical College of Virginia, Richmond.
Herlong
H F
HF
Diehl
A M
AM
Shaw
E W
EW
Combes
B
B
Fallon
H J
HJ
Maddrey
W C
WC
D000328:Adult; D000368:Aged; D001663:Bilirubin / Q000097:blood; D002986:Clinical Trials as Topic; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D005260:Female; D006501:Hepatic Encephalopathy / Q000188:drug therapy; D006519:Hepatitis, Alcoholic / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011379:Prognosis; D011517:Prothrombin Time; D011897:Random Allocation
D001663:Bilirubin; D008775:Methylprednisolone