Impact of rifaximin on cirrhosis complications and gastric microbiota in patients with gastroesophageal variceal bleeding: A pilot randomized controlled trial

Objectives: The application of rifaximin, a non-absorbable antibiotic, in hepatic encephalopathy (HE) has been well established; however, its effect on other complications in cirrhotic patients with previous gastroesophageal variceal bleeding (GEVB) remains unclear. Therefore, we performed a pilot randomized controlled trial aiming to evaluate the impact of rifaximin on cirrhosis-related complications and changes in gastric microbiota.

Methods: Eighty cirrhotic patients who received prophylactic endoscopic treatment for variceal rebleeding were randomly assigned to the control or rifaximin treatment group (rifaximin 400 mg twice daily for 8 weeks). Primary outcome was the total liver-related score, consisting of changes in cirrhosis-related complications including rebleeding, ascites, HE and portal vein thrombosis (PVT). The 16S rDNA sequencing analysis was conducted with gastric lavage fluid samples for the analysis of gastric microbiota.

Results: During the 8-week follow-up, the total liver-related score decreased significantly upon rifaximin therapy (-0.35 ± 0.14 vs 0.05 ± 0.14, p = 0.0465) as well as serum C-reactive protein (CRP) (p = 0.019) and interleukin-8 (p = 0.025) compared with the control group. The rate of PVT recanalization was significantly higher in the rifaximin group (p = 0.012). Prominent difference in gastric microbiota between the two groups was observed, and the rifaximin group had a higher abundance of several taxa which were dysregulated in the progression of cirrhosis. CRP was correlated with several taxa including Alphaproteobacteria, Rhizobiales and Collinsella.

Conclusions: Rifaximin may improve cirrhosis-related complications, including PVT, in patients with previous GEVB through anti-inflammatory and microbiota-modulating functions.

Trial registration number: NCT02991612.