A Meta-analysis on the Role of Probiotics in the Prevention of Overt Hepatic Encephalopathy

Abstract

Overt hepatic encephalopathy (OHE) is a strong predictor of subsequent episodes of OHE, hospitalizations and mortality. Latest practice guidelines have yet to recommend any treatment for the primary prophylaxis of OHE. Lactulose has been the mainstay of treatment only for secondary prophylaxis, but its use suffers from side effects. Probiotics in recent trials have been found to be effective in preventing the occurrence of OHE without the side effects associated with lactulose. Comprehensive literature search of PubMed, Cochrane Central Register of Controlled Trials, EMBASE and reference lists was done. Studies on adults with liver cirrhosis, without OHE at the time of enrollment, with at least 1 month follow-up period, were included. The authors independently reviewed each included trial. Quality of included studies was assessed using the Cochrane Collaboration’s tool for evaluating risk of bias. Seven studies were included in the meta-analysis. Probiotics significantly reduced the development of OHE (RR (CI 95%): 0.49[0.37,0.65], P<0.00001), regardless of history of prior OHE. As primary prophylaxis and secondary prophylaxis, probiotics significantly reduced the development of OHE (Primary: RR (CI 95%): 0.52[0.28,0.95], P=0.03; Secondary: RR (95% CI): 0.64[0.48,0.85], P=0.002). Probiotics did not provide any mortality benefit, whether given as primary or secondary prophylaxis (Overall: RR (CI 95%): 0.79[0.53,1.19], P=0.26; Primary: RR (CI 95%): 0.80[0.30,2.14], P=0.67; Secondary: RR (CI 95%): 0.77[0.49,1.23], P=0.68). Probiotics, whether as primary or secondary prophylaxis, are effective in preventing OHE in patients with liver cirrhosis. Role of probiotics in reducing mortality is still uncertain. Studies with larger sample sizes and longer duration are recommended.