Hepatology. 2021 Jan 9. doi: 10.1002/hep.31708. Online ahead of print.
Rifaximin is an oral non-systemic antibiotic, with minimal gastrointestinal absorption and broad-spectrum antibacterial activity covering both grampositive and gramnegative organisms. Rifaximin is currently worldwide used in patients with cirrhosis for preventing recurrent hepatic encephalopathy because its efficacy and safety has been proved by large randomized clinical trials. In the last decade, experimental and clinical evidence suggest that rifaximin could have other beneficial effects on the course of cirrhosis by modulating the gut microbiome and affecting the gut-liver axis, which, in turn, can interfere with major events of the pathophysiological cascade underlying decompensated cirrhosis, such as systemic inflammatory syndrome, portal hypertension, and bacterial infections. However, the use of rifaximin for prevention or treatment of other complications, including spontaneous bacterial peritonitis or other bacterial infections, is not accepted as evidence by clinical trials is still very weak. The present review deals in the first part with the potential impact of rifaximin on pathogenic mechanisms in liver diseases, whereas, in the second part, its clinical effects are critically discussed. It clearly emerges that, due to its potential activity on multiple pathogenic events, the efficacy of rifaximin in the prevention or management of complications other than hepatic encephalopathy deserves to be investigated extensively. The results of double-blinded, adequately powered randomized clinical trials assessing the effect of rifaximin, alone or in combination with other drugs, on hard clinical endpoints, such as decompensation of cirrhosis, acute-on-chronic liver failure and mortality, are therefore eagerly awaited.