Nina Kimer1,2, Julie S Pedersen1, Juliette Tavenier3, Jeffrey E Christensen4,5, Troels M Busk2, Lise Hobolth1,6, Aleksander Krag7, Waleed Abu Al-Soud8, Martin S Mortensen8, Søren J Sørensen8, Søren Møller2, Flemming Bendtsen1. 1. Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. 2. Centre of Diagnostic Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. 3. Clinical Research Centre, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. 4. Vaiomer SAS, Toulouse, France. 5. Institute of Cardiovascular and Metabolic Diseases (I2MC), INSERM U1048, Toulouse, France. 6. Department of Gastroenterology and Hepatology, Copenhagen University Hospital Bispebjerg, Bispebjerg, Denmark. 7. Department of Gastroenterology and Hepatology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. 8. Section of Microbiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Abstract
BACKGROUND AND AIM: Decompensated cirrhosis is characterized by disturbed hemodynamics, immune dysfunction, and high risk of infections. Translocation of viable bacteria and bacterial products from the gut to the blood is considered a key driver in this process. Intestinal decontamination with rifaximin may reduce bacterial translocation (BT) and decrease inflammation. A randomized, placebo-controlled trial investigated the effects of rifaximin on inflammation and BT in decompensated cirrhosis. METHODS:Fifty-four out-patients with cirrhosis and ascites were randomized, mean age 56 years (± 8.4), and model for end-stage liver disease score 12 (± 3.9). Patients received rifaximin 550-mg BD (n = 36) or placebo BD (n = 18). Blood and fecal (n = 15) sampling were conducted at baseline and after 4 weeks. Bacterial DNA in blood was determined by real-time qPCR 16S rRNA gene quantification. Bacterial composition in feces was analyzed by 16S rRNA gene sequencing. RESULTS:Circulating markers of inflammation, including tumor necrosis factor alpha, interleukins 6, 10, and 18, stromal cell-derived factor 1-α, transforming growth factor β-1, and high sensitivity C-reactive protein, were unaltered by rifaximin treatment. Rifaximin altered abundance of bacterial taxa in blood marginally, only a decrease in Pseudomonadales was observed. In feces, rifaximin decreased bacterial richness, but effect on particular species was not observed. Subgroup analyses on patients with severely disturbed hemodynamics (n = 34) or activated lipopolysaccharide binding protein (n = 37) revealed no effect of rifaximin. CONCLUSION: Four weeks of treatment with rifaximin had no impact on the inflammatory state and only minor effects on BT and intestinal bacterial composition in stable, decompensated cirrhosis (NCT01769040).
RCT Entities:
BACKGROUND AND AIM: Decompensated cirrhosis is characterized by disturbed hemodynamics, immune dysfunction, and high risk of infections. Translocation of viable bacteria and bacterial products from the gut to the blood is considered a key driver in this process. Intestinal decontamination with rifaximin may reduce bacterial translocation (BT) and decrease inflammation. A randomized, placebo-controlled trial investigated the effects of rifaximin on inflammation and BT in decompensated cirrhosis. METHODS: Fifty-four out-patients with cirrhosis and ascites were randomized, mean age 56 years (± 8.4), and model for end-stage liver disease score 12 (± 3.9). Patients received rifaximin 550-mg BD (n = 36) or placebo BD (n = 18). Blood and fecal (n = 15) sampling were conducted at baseline and after 4 weeks. Bacterial DNA in blood was determined by real-time qPCR 16S rRNA gene quantification. Bacterial composition in feces was analyzed by 16S rRNA gene sequencing. RESULTS: Circulating markers of inflammation, including tumor necrosis factor alpha, interleukins 6, 10, and 18, stromal cell-derived factor 1-α, transforming growth factor β-1, and high sensitivity C-reactive protein, were unaltered by rifaximin treatment. Rifaximin altered abundance of bacterial taxa in blood marginally, only a decrease in Pseudomonadales was observed. In feces, rifaximin decreased bacterial richness, but effect on particular species was not observed. Subgroup analyses on patients with severely disturbed hemodynamics (n = 34) or activated lipopolysaccharide binding protein (n = 37) revealed no effect of rifaximin. CONCLUSION: Four weeks of treatment with rifaximin had no impact on the inflammatory state and only minor effects on BT and intestinal bacterial composition in stable, decompensated cirrhosis (NCT01769040).
Authors: Danica Bajic; Adrian Niemann; Anna-Katharina Hillmer; Raquel Mejias-Luque; Sena Bluemel; Melissa Docampo; Maja C Funk; Elena Tonin; Michael Boutros; Bernd Schnabl; Dirk H Busch; Tsuyoshi Miki; Roland M Schmid; Marcel R M van den Brink; Markus Gerhard; Christoph K Stein-Thoeringer Journal: J Crohns Colitis Date: 2020-10-05 Impact factor: 9.071