Research in context
infection, alcohol-related hepatitis, cirrhosis, reduced hepatic inflammation
CIRRHOSIS, LIVER FIBROSIS, LIVER DISEASE, NON-ALCOHOLIC FATTY LIVER DISEASE, INFECTION, ALCOHOL-RELATED LIVER DISEASE, HEPATIC ENCEPHALOPATHY, REGRESSION, COMPLICATIONS

We searched Medline for full papers published in any language in peer-reviewed journals up to Sep 1, 2022, with the term “rifaximin” and filtered by “clinical trial” and identified 138 papers. We manually reviewed the files and identified 37 papers reporting results of randomised controlled trials of rifaximin in patients with liver disease. Among these, 35 trials studied the effect of rifaximin in preventing or treating complications of cirrhosis, one study included patients with alcohol-related hepatitis, and one study included patients with non-alcoholic fatty liver disease. Most studies used doses around 600 mg twice daily in treatment periods up to 6 months and reported that rifaximin is effective and safe to prevent hepatic encephalopathy. These results are supported by several meta-analyses. However, no studies evaluated the efficacy of rifaximin-α in liver fibrosis and its safety in patients with alcohol-related liver disease.
GALA-RIF, an 18-month investigator-initiated, randomised, double-blind, placebo-controlled trial, showed that rifaximin-α did not lead to regression of liver fibrosis in patients with alcohol-related liver disease. However, rifaximin-α appears to reduce progression of liver fibrosis with a number needed to treat of six. As a possible explanation of this beneficial effect, rifaximin-α also reduced hepatic inflammation. Furthermore, long-term treatment with rifaximin-α was well tolerated and we observed no cases of infection with multidrug resistant bacteria or 
Our findings showing that rifaximin-α seems to reduce progression of liver fibrosis represent a major clinical breakthrough in the management of alcohol-related liver disease. The EASL–