Journal Article

Antifibrotic and molecular aspects of rifaximin in alcoholic liver disease: study protocol for a randomized controlled trial

Arumugan, Manimozhiyan, Havelund, Troels, Israelsen, Mads, Madsen, Bjørn Stæhr, Trebicka, Jonel, Thiele, Maja, Krag, Aleksander

2018

Overview

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 alcoholic fibrosis (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 gut microbiota are an important promoter of alcoholic liver disease, current results may open new therapeutic avenues and revolutionize the current understanding of chronic liver diseases. Trial registration EudraCT, 2014–001856-51 . Registered on 16 August 2014.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Alcohol / Alcoholic liver disease / Anti-Bacterial Agents - adverse effects / Anti-Bacterial Agents - therapeutic use / Antibiotics / Bacteria - classification / Bacteria - drug effects / Bacteria - genetics / Biomedicine / Biopsy / Chronic illnesses / Cytokines / Denmark / Development and progression / DNA sequencing / Dosage and administration / Double-Blind Method / Drinking (Alcoholic beverages) / Feces - microbiology / Gastrointestinal Microbiome - drug effects / Growth factors / Gut microbiota / Health aspects / Health Sciences / Health surveys / Hepatology / Humans / Investigations / Liver - drug effects / Liver - pathology / Liver cirrhosis / Liver Cirrhosis, Alcoholic - diagnosis / Liver Cirrhosis, Alcoholic - drug therapy / Liver Cirrhosis, Alcoholic - microbiology / Liver diseases / Liver fibrosis / Medicine / Medicine & Public Health / Microbiota / Pharmacy / Questionnaires / Randomized Controlled Trials as Topic / Ribotyping / Rifaximin / Rifaximin - adverse effects / Rifaximin - therapeutic use / Risk factors / RNA polymerase / School dropout programs / School dropouts / Statistics for Life Sciences / Study Protocol / Time Factors / Treatment Outcome