Meta-analysis: the effects of gut flora modulation using prebiotics, probiotics and synbiotics on minimal hepatic encephalopathy

BACKGROUND: Minimal hepatic encephalopathy (MHE) is characterised by subtle neurocognitive deficits without overt clinical manifestations. Although several trials have individually evaluated the role of prebiotics, probiotics and synbiotics, there is yet no consensus on the management of MHE. AIM: To estimate the efficacy of prebiotics, probiotics and synbiotics in MHE in randomised controlled trials. METHODS: MEDLINE, EMBASE, CINAHL and the Cochrane Database of Systematic Reviews were searched for published studies in all languages. Inclusion and exclusion criteria were defined a priori. Pooled relative risk and heterogeneity were estimated as the measures of association. RESULTS: Nine studies met our inclusion criteria. Use of prebiotics, probiotics and synbiotics significantly reduced the pooled relative risk (RR) of no improvement of MHE (RR 0.40, 95% CI 0.32-0.50; P<0.001). Upon subgroup analysis, five studies with lactulose showed significant reduction of risk of no improvement of MHE (RR 0.34, 95% CI 0.24-0.47; P<0.0001) with no inter-trial heterogeneity. In two trials each of probiotics and synbiotics, their use was associated with significant beneficial effects (RR 0.41, 95% CI 0.26-0.65; P<0.0001 and RR of 0.51, 95% CI 0.32-0.80; P=0.004 respectively). There were no major adverse events though probiotics and synbiotics were better tolerated than lactulose. CONCLUSIONS: The use of prebiotics, probiotics and synbiotics was associated with significant improvement in minimal hepatic encephalopathy. Among individual agents, lactulose appears to have the most beneficial effect, followed closely by probiotics and synbiotics.