Full title
Additional file 1: of Antifibrotic and molecular aspects of rifaximin in alcoholic liver disease: study protocol for a randomized controlled trial
Authors
Bjørn Stæhr Madsen; Jonel Trebicka; Thiele, Maja; Israelsen, Mads; Manimozhiyan Arumugan; Havelund, Troels; Krag, Aleksander
Abstract
Background
Alcoholic liver disease is the leading cause of cirrhosis worldwide. Due to an increase in alcohol overuse,alcoholic liver disease has become an increased burden on health care systems. Abstinence from alcohol remains the
cornerstone of alcoholic liver disease treatment; however, this approach is hampered by frequent relapse and lack of
specific therapy for treating advanced cases of liver disease. In the present study, we hypothesized that gut microbiota
drive the development of liver fibrosis and that modulation of gut microbiota with the gut-selective, nonabsorbable
antibiotic rifaximin attenuates alcoholic liver fibrosis.
Methods/design
Our double-blind, placebo-controlled trial will include 136 participants with biopsy-verified alcoholicfibrosis (Ishak liver fibrosis score of 1–4). Participants are randomized 1:1 to receive placebo or 550 mg of rifaximin twice
daily for 18 months. A liver biopsy will be performed at the end of the treatment period to evaluate the effect of drug
treatment on liver fibrosis. Stool, urine, and saliva specimens will be collected before treatment begins, at 1 month, and
at the end of the treatment period. Fecal samples are used for microbiome deep sequencing. Changes in microbiome
composition are compared before and after the trial medication period and linked to changes in liver fibrosis.
Discussion
This is the first clinical trial to evaluate the effect of gut microbiota on liver fibrosis in humans. If gutmicrobiota are an important promoter of alcoholic liver disease, current results may open new therapeutic avenues and
revolutionize the current understanding of chronic liver diseases.