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Trials. 2018 Feb 26;19(1):143. doi: 10.1186/s13063-018-2523-9.

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

Author information

1
Department of Gastroenterology and Hepatology, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark. bjoern.staehr.madsen@rsyd.dk.
2
OPEN, Odense Patient Data Exploratory Network, Odense University Hospital, J.B. Winsløws Vej 9 a, 3 Floor, 5000, Odense C, Denmark. bjoern.staehr.madsen@rsyd.dk.
3
Department of Internal Medicine, University of Bonn, Sigmund Freud Str. 25, 53127, Bonn, Germany.
4
Institute of Clinical Research, University of Southern Denmark, Windsløwparken 19, 3 floor, 5000, Odense C, Denmark.
5
European Foundation for the Study of Chronic Liver Failure - EF Clif, Travessera de Gràcia, 11, 7th floor, 08021, Barcelona, Spain.
6
Institute for Bioengineering of Catalonia, C. Baldiri Reixac 10-12, 08028, Barcelona, Spain.
7
Department of Gastroenterology and Hepatology, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark.
8
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.

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 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.

KEYWORDS:

Alcoholic liver disease; Gut microbiota; Liver fibrosis; Rifaximin

PMID:
29482588
PMCID:
PMC5828001
DOI:
10.1186/s13063-018-2523-9
[Indexed for MEDLINE]
Free PMC Article

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