A Rambaldi1, H H Saconato, E Christensen, K Thorlund, J Wetterslev, C Gluud. 1. The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Abstract
BACKGROUND: Glucocorticosteroids versus placebo or no intervention for patients with alcoholic hepatitis have been evaluated for more than 35 years. However, the results of randomized trials and meta-analyses differ substantially. AIM: To review all randomized clinical trials of glucocorticosteroids vs. placebo or no intervention for patients with alcoholic hepatitis. METHODS: We searched for randomized trials published before July 2007. The trials were assessed for risk of bias. RESULTS: We included 15 trials with a total of 721 randomized patients. The overall mortality rate was 39.5%. Twelve of the fifteen trials were at risk of bias. Glucocorticosteroids did not statistically reduce mortality compared with placebo or no intervention (relative risk 0.83, 95% CI 0.63-1.11). Glucocorticosteroids significantly reduced mortality in the subgroup of trials with patients with Maddrey's score of at least 32 or hepatic encephalopathy and with low-bias risk. In all analyses, heterogeneity was significant and substantial. Trial sequential analyses using heterogeneity-adjusted information size demonstrated no significant effect of glucocorticosteroids on mortality. Weighted logistic regression analyses taking prognostic factors at randomization into consideration found no significant effect of glucocorticosteroids on mortality. CONCLUSIONS: The current evidence base of mainly heterogeneous with high bias risk trials does not support the use of glucocorticosteroids in alcoholic hepatitis. Large, low-bias risk placebo-controlled randomized trials are needed.
BACKGROUND:Glucocorticosteroids versus placebo or no intervention for patients with alcoholic hepatitis have been evaluated for more than 35 years. However, the results of randomized trials and meta-analyses differ substantially. AIM: To review all randomized clinical trials of glucocorticosteroids vs. placebo or no intervention for patients with alcoholic hepatitis. METHODS: We searched for randomized trials published before July 2007. The trials were assessed for risk of bias. RESULTS: We included 15 trials with a total of 721 randomized patients. The overall mortality rate was 39.5%. Twelve of the fifteen trials were at risk of bias. Glucocorticosteroids did not statistically reduce mortality compared with placebo or no intervention (relative risk 0.83, 95% CI 0.63-1.11). Glucocorticosteroids significantly reduced mortality in the subgroup of trials with patients with Maddrey's score of at least 32 or hepatic encephalopathy and with low-bias risk. In all analyses, heterogeneity was significant and substantial. Trial sequential analyses using heterogeneity-adjusted information size demonstrated no significant effect of glucocorticosteroids on mortality. Weighted logistic regression analyses taking prognostic factors at randomization into consideration found no significant effect of glucocorticosteroids on mortality. CONCLUSIONS: The current evidence base of mainly heterogeneous with high bias risk trials does not support the use of glucocorticosteroids in alcoholic hepatitis. Large, low-bias risk placebo-controlled randomized trials are needed.
Authors: Damien A Bellos; Dhara Sharma; Megan R McMullen; Jeanette Wat; Paramananda Saikia; Carol A de la Motte; Laura E Nagy Journal: Alcohol Clin Exp Res Date: 2019-07-16 Impact factor: 3.455