Rifaximin has minor effects on bacterial composition, inflammation and bacterial translocation in cirrhosis; A randomized trial

BACKGROUND & AIMS: Decompensated cirrhosis is characterized by disturbed haemodynamics, 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. In 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 MELD score 12 (±3.9). Patients received rifaximin 550 mg BD (n=36) or placebo BD (n=18). Blood and faecal (n=15) sampling were conducted at baseline and after four weeks. Bacterial DNA in blood was determined by real-time qPCR 16S rRNA gene quantification. Bacterial composition in faeces was analysed by 16S rRNA gene sequencing.

RESULTS: Circulating markers of inflammation, including TNFα, interleukin-6, 10 and 18, Stromal cell-derived factor 1-α, transforming growth factor β-1 and high sensitivity CRP, were unaltered by rifaximin treatment. Rifaximin altered abundance of bacterial taxa in blood marginally, only a decrease in Pseudomonadales was observed. In faeces, rifaximin decreased bacterial richness, but effect on particular species was not observed. Subgroup analyses on patients with severely disturbed hemodynamics (n=34); or activated LBP (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).