Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy.
BACKGROUND
Rifaximin is recommended for prevention of hepatic encephalopathy (HE). The effects of rifaximin on overt and minimal HE are debated.


OBJECTIVE
To perform a systematic review and meta-analysis of randomised controlled trials (RCTs) on rifaximin for HE.


METHODS
We performed electronic and manual searches, gathered information from the U.S. Food and Drug Administration Home Page, and obtained unpublished information on trial design and outcome measures from authors and pharmaceutical companies. Meta-analyses were performed and results presented as risk ratios (RR) with 95% confidence intervals (CI) and the number needed to treat. Subgroup, sensitivity, regression and sequential analyses were performed to evaluate the risk of bias and sources of heterogeneity.


RESULTS
We included 19 RCTs with 1370 patients. Outcomes were recalculated based on unpublished information of 11 trials. Overall, rifaximin had a beneficial effect on secondary prevention of HE (RR: 1.32; 95% CI 1.06-1.65), but not in a sensitivity analysis on rifaximin after TIPSS (RR: 1.27; 95% CI 1.00-1.53). Rifaximin increased the proportion of patients who recovered from HE (RR: 0.59; 95% CI: 0.46-0.76) and reduced mortality (RR: 0.68, 95% CI 0.48-0.97). The results were robust to adjustments for bias control. No small study effects were identified. The sequential analyses only confirmed the results of the analysis on HE recovery.


CONCLUSIONS
Rifaximin has a beneficial effect on hepatic encephalopathy and may reduce mortality. The combined evidence suggests that rifaximin may be considered in the evidence-based management of hepatic encephalopathy.
Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; Department of Clinical Physiology and Nuclear Medicine, Centre of Functional Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
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D015982:Bias; D006501:Hepatic Encephalopathy / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D016017:Odds Ratio; D020011:Protective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012294:Rifamycins / Q000009:adverse effects / Q000627:therapeutic use*; D000078262:Rifaximin; D055502:Secondary Prevention
D020011:Protective Agents; D012294:Rifamycins; D000078262:Rifaximin