Combination therapy with rifaximin and lactulose in hepatic encephalopathy: A systematic review and meta-analysis

Rifaximin and lactulose are widely used in patients with hepatic encephalopathy (HE); however, data on whether the combined use of rifaximin and lactulose could yield additional benefits for patients with HE are limited and inconclusive. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the treatment effectiveness of rifaximin plus lactulose versus lactulose alone in patients with HE. Electronic databases (PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure) were searched for eligible RCTs from their inception until November 2020. Relative risks (RRs) with 95% confidence intervals (CIs) were applied to calculate pooled effect estimates for the treatment effectiveness of rifaximin plus lactulose versus lactulose alone by using the random-effects model. Sensitivity, subgroup, and publication bias analyses were also performed. We included 7 RCTs enrolling 843 patients with HE. We noted that the use of rifaximin plus lactulose was associated with an increased incidence of effective rate than lactulose alone (RR, 1.30; 95% CI, 1.10-1.53; P = 0.002). Moreover, the use of rifaximin plus lactulose was associated with a reduced risk of mortality as compared with lactulose alone (RR, 0.57; 95% CI, 0.41-0.80; P = 0.001). This study found that the use of rifaximin in combination with lactulose could provide additional benefits in terms of increased effective rate and decreased mortality than lactulose alone in patients with HE.