Abstract
Introduction: Hepatic Encephalopathy (HE) is a serious complication of chronic liver disease characterized by complex neuropsychiatric abnormalities that range from mild confusion to coma. Although there have been different treatment options for HE, lactulose (a nonabsorbable disaccharide, NADS) has been most commonly used and remains the mainstay of therapy. Rifaximin is a non-absorbable antibiotic and was recently approved by FDA for prevention of recurrent HE. Several small trials in the past have compared the effectiveness of rifaximin and NADS in management of HE. The results of these trials have been conflicting and limited due to small number of subjects involved. Aim: We therefore conducted a metaanalysis of Randomized controlled trials (RCT) to evaluate the efficacy of rifaximin in comparison to NADS. Methods: Two reviewers searched MEDLINE, EMBASE, CINAHL and the Cochrane Database using search terms “hepatic encephalopathy”, “rifaximin, “lactulose”, “lactitol”, “non-absorbable disaccharides”, “cirrhosis”. Inclusion criteria were:1) Studies involving patients with HE 2) study be a RCT 3) comparison of rifaximin with NADS (either lactulose or lactitol). The review was done per guidelines of PRISMA statement and methodological quality evaluated using Jadad scoring system. The results were pooled and relative risk ratio and 95% confidence interval (95% CI) derived using fixed effect estimates using STATA 10. Results: Five studies with a total of 259 patients met the pre-specified inclusion criteria. Of these 134 were randomized to rifaximin while 125 to NADS. In comparison to NADS, use of rifaximin was associated with significant reduction in risk of no improvement of HE (RR 0.57, 95% CI 0.35 0.94, p = 0.028). There was no significant heterogeneity amongst studies with Chi square statistic = 3.9, p = 0.41, I squared statistic = 0.0%. Discussion: Rifaximin is more beneficial in comparison to NADS in management of HE. Although Lactulose is used as the first line agent, frequent side effects such as bloating, flatulence, diarrhea limit tolerability. Rifaximin is not absorbed systemically and thus better tolerated. Further research should explore the optimum treatment duration for HE and costanalysis with use of rifaximin.
Published Version
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