Systematic review and meta-analysis of randomized trials on probiotics for hepatic encephalopathy


Dr Kathrine Holte, Department of Surgical Gastroenterology 435, Hvidovre University Hospital, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. Email:


Aim:  The objective of this systematic review and meta-analysis was to assess the efficacy of probiotics and synbiotics in patients with hepatic encephalopathy.

Methods:  Eligible trials were identified by searching electronic databases including MEDLINE, the Cochrane Library, Science Citation Index and Embase, abstract proceedings, reference lists and ongoing trial registers until 13 October 2010. We included randomized controlled trials comparing probiotics and synbiotics with no intervention, placebo or lactulose in patients with hepatic encephalopathy. The primary outcome measure was improvement in hepatic encephalopathy. Results were expressed as risk rates (RR) with confidence intervals (CI) and intertrial heterogeneity as I2.

Results:  Seven trials with a total of 393 patients were analyzed. Compared to placebo or lactulose, treatment with probiotics or synbiotics significantly improved hepatic encephalopathy (RR = 1.40, 95% CI = 1.05–1.86, I2 = 5%). Probiotics decreased arterial ammonia (weighted mean difference 15.95; 95% CI = 26.72–3.28; I2 = 68%), but not venous ammonia (weighted mean difference 5.23; 95% CI = 21.77–11.30; I2 = 89%). Treatment with probiotics or synbiotics did not significantly affect the psychometric tests. Overall adverse events were reported in four trials with no difference between probiotics and placebo groups (RR = 0.32, 95% CI = 0.04–2.57; I2 = 59%). Regression analysis showed evidence of small-study effects.

Conclusion:  The present meta-analysis suggests that probiotics may be an effective treatment of hepatic encephalopathy, though rigorous evaluation in standardized, randomized, clinical trial with clinically relevant outcomes is still needed.