Therapeutic Duel of Rifaximin Versus Lactulose in Hepatic Encephalopathy: A Systematic Review

Abstract

This systematic review aimed to compare the clinical efficacy of rifaximin versus lactulose in the management of hepatic encephalopathy (HE) by analyzing evidence from randomized controlled trials (RCTs). A comprehensive search across major databases identified seven eligible RCTs encompassing 693 adult patients diagnosed with overt or minimal HE. Findings demonstrated that rifaximin is at least as effective as lactulose in reversing HE symptoms, with some studies reporting significantly higher HE reversal rates when rifaximin was used in combination with lactulose (e.g., 76% vs. 50.8%, p<0.004), reduced mortality (23.8% vs. 49.1%, p<0.05), and shorter hospital stays (5.8 vs. 8.2 days, p=0.001). While other trials reported similar efficacy between the two agents (e.g., HE improvement: 84.4% vs. 95.4%, p=0.315), rifaximin was generally associated with better tolerability and fewer gastrointestinal side effects. These results support rifaximin as an effective and well-tolerated therapeutic option, either as monotherapy or in combination with lactulose. Further large-scale, multicenter trials are warranted to assess long-term outcomes, recurrence rates, and cost-effectiveness.

Keywords: cirrhosis; hepatic encephalopathy; lactulose; neurocognitive impairment; randomized controlled trial; rifaximin; treatment efficacy.

Figure 1. The PRISMA flowchart represents the study selection process.

PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses