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

Background & Aims: 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 decompensated cirrhosis and HE were included. Study selection followed PRISMA guidelines. Data extraction focused on study design, population, treatment, and QoL outcomes. Results: Out of 4,343 records screened, 10 studies met the inclusion criteria. Most studies evaluated rifaximin in comparison with placebo and focused on patients with minimal or covert HE. Rifaximin was almost consistently associated with statistically significant improvements in overall and domain-specific QoL scores compared with placebo, particularly in fatigue, activity and emotional function. 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. One study reported greater improvement in QoL with nitazoxanide, although rifaximin showed significant improvements in specific QoL domains. Conclusion: Rifaximin is associated with improvements in QoL in patients with cirrhosis and HE, with benefits observed across multiple domains and outcomes comparable to alternative therapies. Further high-quality comparative trials, particularly in patients with overt HE and in prophylactic settings, are needed to confirm these findings and to better inform patient-centered management strategies.