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Background: Randomized controlled trials testing flumazenil in hepatic encephalopathy have shown conflicting results. Aim: To compare flumazenil and placebo in hepatic encephalopathy in patients with cirrhosis. Methods: An overview of randomized controlled trials comparing flumazenil and placebo in hepatic encephalopathy in patients with cirrhosis was performed. For each end‐point, heterogeneity and treatment efficacy were assessed by Peto and Der Simonian methods. As most trials were crossover in nature, a sensitivity analysis was performed including the two treatment periods. Results: Six double‐blind randomized controlled trials, including 641 patients (326 treated with flumazenil and 315 with placebo), were identified. The treatment duration ranged from 5 min to 3 days. Heterogeneity tests between control groups were not significant. The mean percentages of patients with clinical improvement (five trials) were 27% in treated groups and 3% in placebo groups. This difference was significant by both methods (Peto: odds ratio=6.15; 95% confidence interval, 4.0–9.5; P < 0.001; Der Simonian: mean rate difference, 29%; 95% confidence interval, 17–41; P < 0.001). The mean percentages of patients with electroencephalographic improvement were 19% in treated groups and 2% in placebo groups. This difference was significant only with the Peto method (odds ratio=5.8; 95% confidence interval, 3.4–9.7; P < 0.001). The sensitivity analysis showed similar results. Conclusions: This meta‐analysis shows that flumazenil induces clinical and electroencephalographic improvement of hepatic encephalopathy in patients with cirrhosis.

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Chronic administration of cyclosporin A may induce cholestasis in a few patients. The purpose of this study was to examine the effect of chronic administration of cyclosporin A on serum bile acid levels, serum bilirubin concentration, and bromosulfophthalein plasmatic fractional clearance. Twenty heart-transplanted patients with normal serum alanine aminotransferase activity receiving cyclosporine A during a mean duration of 33 months (range 7-54) were compared to 20 matched kidney-transplanted patients with normal serum alanine aminotransferase receiving azathioprine for a mean duration of 34 months (range 6-72). As compared to azathioprine-treated patients, patients treated with cyclosporin A had an increase in serum bile acid levels of 32% (P < 0.01), an increase in serum bilirubin concentration of 100% (P < 0.001), and a decrease in bromosulfophthalein plasmatic fractional clearance of 60% (P < 0.001). These results suggest that cyclosporin A induces a decrease in hepatic excretory function in man.