Quality of Life in Patients with Hepatic Encephalopathy Treated with Rifaximin: A Systematic Review

Background/Objectives: Hepatic encephalopathy (HE) significantly impairs quality of life (QoL) in patients with cirrhosis. While rifaximin is established in HE treatment and prevention, its specific impact on QoL remains less clearly defined. This systematic review aims to evaluate the effects of rifaximin on QoL in patients with HE. Methods: A comprehensive literature search was conducted in MEDLINE/PubMed, Embase, and CENTRAL through November 2025. Clinical studies evaluating rifaximin’s impact on QoL in patients with cirrhosis and minimal/covert or recurrent overt HE were included. Study selection followed PRISMA guidelines. Data extraction focused on study design, population, treatment, and QoL outcomes. Results: Out of 4343 records screened, 10 studies met the inclusion criteria. Several studies evaluated rifaximin in comparison with placebo and focused on patients with minimal or covert HE. Rifaximin was generally associated with improvements in overall and domain-specific QoL scores compared with placebo. These benefits were observed across different dosages and treatment durations. In comparative studies, rifaximin showed QoL outcomes comparable to those of lactulose, L-ornithine L-aspartate, and combination regimens. Conclusions: Rifaximin may be associated with improvements in QoL in patients with cirrhosis and HE, with benefits observed across multiple domains and outcomes broadly comparable to alternative therapies. However, given the limitations of available evidence and the heterogeneity in study designs, HE phenotypes, QoL instruments, and outcome reporting, these findings should be interpreted with caution. Further high-quality comparative trials, particularly in patients with recurrent overt HE and in prophylactic settings, are needed to confirm these findings.