Efficacy and safety of rifaximin for the prophylaxis of hepatic encephalopathy: A meta-analysis

Background and aim:The efficacy of rifaximin in the prevention of overt hepatic encephalopathy (HE) has not been established. The aim of this study was to access the efficacy and safety of rifaximin in the prophylaxis of HE.Methods:We conducted a meta-analysis search of the Cochrane Library, PubMed, ClinicalTrials.gov, Web of Science, and EMBASE as of March 2022. We pooled data by random-effects DerSimonian-Laird models to calculate hazard ratios (relative risks, RRs) for mortality, incidence of HE, and adverse events.Results:Fourteen randomized controlled trials were included in the study. Rifaximin helped prevent HE (RR = -0.47, 95% confidence interval [CI]: -0.68 to -0.26) in patients with cirrhosis, but did not reduce mortality (RR = 0.03, 95% CI: -0.32 to 0.39) or increase the occurrence of adverse events (RR = -0.08, 95% CI: 0.22-0.07). Subgroup analysis showed that rifaximin was effective in both the primary (RR = 1.17, 95% CI: 1.06-1.29) and secondary (RR = 1.17, 95% CI: 1.06-1.29) prevention of HE. Moreover, subgroup analysis found that rifaximin helped prevent HE in alcohol-related (RR = -0.59, 95% CI: -0.87 to -0.32) or virus-associated (RR = -0.41, 95% CI: -0.71 to -0.11), and underwent transjugular intrahepatic portosystemic shunt (RR = -0.51, 95% CI: -0.76 to -0.27) or non-transjugular intrahepatic portosystemic shunt (RR = -0.35, 95% CI: -0.66 to -0.05) cirrhotic patients. Subgroup analyzed by the intervention, rifaximin versus placebo (RR = -0.43, 95% CI: -0.73 to -0.14) and rifaximin+lactulose versus lactulose (RR = -0.57, 95% CI: -0.68 to -0.26) were statistically significant prevention of HE, rather than rifaximin versus lactulose (RR = -0.44, 95% CI: -1.0 to 0.11).Conclusions:Rifaximin is beneficial for primary and secondary prevention of HE, but it does not reduce mortality or increase the incidence of adverse events in patients with end-stage cirrhosis caused by virus or alcohol.