Clinical Impact of Rifaximin in Liver Cirrhosis: A Critical Review

Abstract

Liver cirrhosis represents a major contributor to global morbidity and mortality, characterised by progressive hepatic fibrosis, portal hypertension, and susceptibility to life-threatening complications including hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), and acute-on-chronic liver failure (ACLF). Rifaximin, a minimally absorbed, broad-spectrum oral antibiotic with gut-selective activity, has progressively emerged as a clinically significant agent in the management of cirrhosis and its sequelae. This critical review synthesises the current evidence base for rifaximin across the principal clinical domains of cirrhosis management, encompassing its well-established role in the secondary prophylaxis of overt HE, its eubiotic effects on the intestinal microbiome, its potential role in SBP prevention, and its emerging indications in portal haemodynamic stabilisation and systemic inflammation reduction. Evidence from landmark randomised controlled trials demonstrates that rifaximin substantially reduces HE recurrence and related hospitalisations, with a favourable long-term safety profile driven principally by its negligible systemic absorption. More tentative data support broader applications in SBP prevention and haemodynamic improvement, while the null result of the APACHE randomised controlled trial has tempered expectations regarding rifaximin as a universal disease-modifier in advanced decompensated cirrhosis. Key unresolved questions persist concerning optimal dosing strategies, combination approaches with lactulose and albumin, cost-effectiveness across diverse healthcare settings, and the long-term consequences of rifaximin on intestinal antimicrobial resistance profiles. This review critically appraises the available evidence across these domains and delineates priority areas for future investigation.