PTU-048 Rifaximin for the treatment of hepatic encephalopathy; a meta-analysis of randomised studies

Introduction The non-absorbable antibiotic rifaximin has been used to treat hepatic encephalopathy (HE) since the 1980s. Interest in its use increased following a recent Phase III study showing that treatment with rifaximin over 6-months resulted in a relative reduction in the risk of breakthrough HE of 58% compared to placebo (Bass et al , 2010). The aim of this study was to evaluate the efficacy and safety of rifaximin for the treatment of all types of HE in patients with cirrhosis against a variety of comparative regimens. Methods A language unrestricted search for papers published between January 1983 and September 2011 was undertaken utilising 11 databases. All HE treatment trials were scrutinised and randomised trials identified. Raw data were obtained from six trials. Data were extracted on (1) the numbers of patients showing improvement overall; (2) the means (±1SD) for mental state, asterixis, number connection tests (NCT), EEG and blood ammonia; and (3) adverse events. Fixed effect model meta-analyses were applied, subdivided by population type. Random effects analyses were used when statistically significant heterogeneity of results occurred. Overall relative proportions were calculated for binary outcomes and standardised mean differences (SMD) for quantitative outcomes. Results 17 trials were identified comparing rifaximin to non-absorbable disaccharides (9 trials), other antibiotics (6 trials) or “no treatment” (2 trials) in patients with either “acute” (4 trials), “chronic” (8 trials), or “minimal” (3 trials) HE or else for the “prevention of HE recurrence” (2 trials). Most trials were of adequate quality; the total sample size was 1037 patients, but data were not extractable for all outcomes. The relative proportion of patients experiencing clinical improvement with rifaximin, compared to all control regimen, was 1.26 (95% CI 1.05 to 1.52, p=0.014). Broadly consistent benefits were shown for individual outcome variables for example, asterixis (SMD −0.32, 95% CI −0.62 to −0.02, p=0.038, 5 trials); EEG (SMD −0.49, 95% CI −0.92 to −0.07, p=0.023, 2 trials) and blood ammonia (SMD=−0.25, 95% CI −0.48 to −0.02, p=0.034, 8 trials), although not for mental status (SMD −0.19, 95% CI −0.47 to 0.10, p=0.20, 5 trials) or NCTs (SMD 0.05, 95% CI −0.19 to 0.28, p=0.8, 7 trials). SMDs were stronger in the eight trials in chronic hepatic encephalopathy (asterixis −0.34; EEG −0.56; blood ammonia −0.26; mental state −0.45; NCTs 0.36). No significant differences were observed in side-effects between rifaximin and control regimens. Conclusion Rifaximin is an efficacious and safe treatment for HE when compared to a variety of other treatments regimens; the benefits are most marked in patients with chronic HE. Competing interests None declared.