Discussion
cirrhosis, infections, Alcohol-related liver disease, fibrosis, liver fibrosis, alcohol-related liver disease, liver inflammation
DECOMPENSATED CIRRHOSIS, CIRRHOSIS, LIVER FIBROSIS, FIBROSIS, INFECTIONS, ALCOHOL-RELATED LIVER DISEASE, REGRESSION
GALA-RIF, an 18-month, randomised, double-blind, placebo-controlled trial, showed that rifaximin-α did not lead to regression of liver fibrosis in patients with biopsy-confirmed alcohol-related liver disease. However, rifaximin-α seemed to reduce progression of liver fibrosis, possibly due to attenuation of liver inflammation, despite a higher self-reported alcohol consumption in the rifaximin-α group during the trial. Our results suggest that rifaximin-α might be beneficial in patients with asymptomatic alcohol-related liver disease by preventing progression to decompensated cirrhosis.Alcohol-related liver disease is the most prevalent cause of cirrhosis in the USA and Europe and liver fibrosis is the main prognostic factor contributing to liver-related morbidity and mortality.In this study, progression of fibrosis over 18 months occurred in 43% of patients in the per-protocol placebo group, which is remarkably higher than the 16–21% over 2 years previously reported by Lieber and colleagues.Bacterial antimicrobial resistance is a major global burden, and long-term use of antibiotics, such as rifaximin-α, could be associated with the development of infections with multidrug-resistant bacteria and This study shows that rifaximin-α is well tolerated and might reduce fibrosis progression. However, the starting point for the treatment of patients with alcohol-related liver disease should be alcohol rehabilitation. Unfortunately, most patients with an alcohol dependence do not achieve long-term abstinence, but have periods of relapse.Strengths of this study include the long intervention period and the histological assessment of liver fibrosis as the primary outcome supported by non-invasive markers. The high compliance in an otherwise vulnerable population strengthens the findings, but individuals with alcohol-related liver disease outside a clinical trial might not have the same compliance, which should be considered if implemented. The main limitation is that no significant difference was noted between groups for the primary endpoint, decrease of liver fibrosis. Preferably, the beneficial effect of rifaximin-α on halting fibrosis progression should be validated in a multicentre, phase 3, confirmatory efficacy trial with hard clinical endpoints. For the inclusion criteria, we used the histological assessment by the on-call pathologist at the hospital. During the masked outcome assessment by the single expert pathologist, seven patients were downgraded from F1 to F0 at baseline and could consequently not reach the primary outcome. Since the proportion of F0 patients was only 5%, and distribution of these patients was balanced between the groups (four In patients with biopsy-confirmed alcohol-related liver disease, 18 months of treatment with rifaximin-α did not promote regression of liver fibrosis, but it did appear to reduce fibrosis progression. These results suggest that rifaximin-α seems to decrease progression of liver fibrosis in patients with alcohol-related liver disease and therefore might be beneficial for individuals who cannot achieve alcohol abstinence.