Rifaximin Has No Effect on Hemodynamics in Decompensated Cirrhosis: A Randomized, Double-Blind, Placebo-Controlled Trial

Decompensated cirrhosis is characterized by disturbed systemic and splanchnic hemodynamics. Bacterial translocation from the gut is considered the key driver in this process. Intestinal decontamination with rifaximin may improve hemodynamics. This double-blind, randomized, controlled trial (clinicaltrials. gov, NCT01769040) investigates the effects of rifaximin on hemodynamics, renal function, and vasoactive hormones. We randomized 54 stable outpatients with cirrhosis and ascites to rifaximin 550 mg twice a day (n = 36) or placebo twice a day (n = 18). Forty-five patients were male, mean age 56 years (68.4), average Child score 8.3 (+/- 1.3), and Model for End-Stage Liver Disease score 11.7 (+/- 3.9). Measurements of hepatic venous pressure gradient, cardiac output, and systemic vascular resistance were made at baseline and after 4 weeks. The glomerular filtration rate and plasma renin, noradrenaline, lipopolysaccharide binding protein, troponin T, and brain natriuretic peptide levels were measured. Rifaximin had no effect on hepatic venous pressure gradient, mean 16.8 +/- 3.8 mm Hg at baseline versus 16.6 +/- 5.3 mm Hg at follow-up, compared to the placebo, mean 16.4 +/- 4 mm Hg at baseline versus 16.3 +/- 4.4 mm Hg at follow-up, P = 0.94. No effect was found on cardiac output, mean 6.9 +/- 1.7 L/min at baseline versus 6.9 +/- 2.3 L/min at follow-up, compared to placebo, mean 6.6 +/- 1.9L/min at baseline compared to 6.5 +/- 2.1 L/min at follow-up, P = 0.66. No effects on the glomerular filtration rate, P = 0.14,or vasoactive hormones were found. Subgroup analyses on patients with increased lipopolysaccharide binding protein and systemic vascular resistance below the mean (1,011 dynes x s/cm(5)) revealed no effect of rifaximin. Conclusion: Four weeks of treatment with rifaximin did not reduce the hepatic venous pressure gradient or improve systemic hemodynamics in patients with cirrhosis and ascites; rifaximin did not affect glomerular filtration rate or levels of vasoactive hormones.