Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial

R. L. Carithers, F. Herlong, A. M. Diehl, E. W. Shaw, B. Combes, H. J. Fallon, W. C. Maddrey

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Abstract

Study Objective: To determine the efficacy of a corticosteroid in reducing the short-term mortality of patients with severe 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 μmol/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. 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 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.

Original languageEnglish (US)
Pages (from-to)685-690
Number of pages6
JournalAnnals of Internal Medicine
Volume110
Issue number9
StatePublished - 1989

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Alcoholic Hepatitis
Methylprednisolone
Multicenter Studies
Placebos
Hepatic Encephalopathy
Therapeutics
Mortality
Prothrombin Time
Random Allocation
Drug-Related Side Effects and Adverse Reactions
Bilirubin
Proportional Hazards Models
Teaching Hospitals
Adrenal Cortex Hormones

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Carithers, R. L., Herlong, F., Diehl, A. M., Shaw, E. W., Combes, B., Fallon, H. J., & Maddrey, W. C. (1989). Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial. Annals of Internal Medicine, 110(9), 685-690.

Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial. / Carithers, R. L.; Herlong, F.; Diehl, A. M.; Shaw, E. W.; Combes, B.; Fallon, H. J.; Maddrey, W. C.

In: Annals of Internal Medicine, Vol. 110, No. 9, 1989, p. 685-690.

Research output: Contribution to journalArticle

Carithers, RL, Herlong, F, Diehl, AM, Shaw, EW, Combes, B, Fallon, HJ & Maddrey, WC 1989, 'Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial', Annals of Internal Medicine, vol. 110, no. 9, pp. 685-690.
Carithers RL, Herlong F, Diehl AM, Shaw EW, Combes B, Fallon HJ et al. Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial. Annals of Internal Medicine. 1989;110(9):685-690.
Carithers, R. L. ; Herlong, F. ; Diehl, A. M. ; Shaw, E. W. ; Combes, B. ; Fallon, H. J. ; Maddrey, W. C. / Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial. In: Annals of Internal Medicine. 1989 ; Vol. 110, No. 9. pp. 685-690.
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abstract = "Study Objective: To determine the efficacy of a corticosteroid in reducing the short-term mortality of patients with severe 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 μmol/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. 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 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.",
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AU - Herlong, F.

AU - Diehl, A. M.

AU - Shaw, E. W.

AU - Combes, B.

AU - Fallon, H. J.

AU - Maddrey, W. C.

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N2 - Study Objective: To determine the efficacy of a corticosteroid in reducing the short-term mortality of patients with severe 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 μmol/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. 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 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.

AB - Study Objective: To determine the efficacy of a corticosteroid in reducing the short-term mortality of patients with severe 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 μmol/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. 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 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.

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