The Use of Rifaximin in the Prevention of Overt Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt : A Randomized Controlled Trial

Ann Intern Med. 2021 May;174(5):633-640. doi: 10.7326/M20-0202. Epub 2021 Feb 2.

Abstract

Background: The efficacy of rifaximin in the secondary prevention of overt hepatic encephalopathy (HE) is well documented, but its effectiveness in preventing a first episode in patients after transjugular intrahepatic portosystemic shunt (TIPS) has not been established.

Objective: To determine whether rifaximin prevents overt HE after TIPS compared with placebo.

Design: Randomized, double-blind, multicenter, placebo-controlled trial. (ClinicalTrials.gov: NCT02016196).

Participants: 197 patients with cirrhosis undergoing TIPS for intractable ascites or prevention of variceal rebleeding.

Intervention: Patients were randomly assigned to receive rifaximin (600 mg twice daily) or placebo, beginning 14 days before TIPS and continuing for 168 days after the procedure.

Measurements: The primary efficacy end point was incidence of overt HE within 168 days after the TIPS procedure.

Results: An episode of overt HE occurred in 34% (95% CI, 25% to 44%) of patients in the rifaximin group (n = 93) and 53% (CI, 43% to 63%) in the placebo group (n = 93) during the postprocedure period (odds ratio, 0.48 [CI, 0.27 to 0.87]). Neither the incidence of adverse events nor transplant-free survival was significantly different between the 2 groups.

Limitations: The study's conclusion applies mainly to patients with alcoholic cirrhosis, who made up the study population. The potential benefit of rifaximin 6 months after TIPS and beyond remains to be investigated.

Conclusion: In patients with cirrhosis treated with TIPS, rifaximin was well tolerated and reduced the risk for overt HE. Rifaximin should therefore be considered for prophylaxis of post-TIPS HE.

Primary funding source: French Public Health Ministry.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ascites / surgery
  • Double-Blind Method
  • Female
  • France
  • Gastrointestinal Agents / therapeutic use*
  • Gastrointestinal Hemorrhage / prevention & control
  • Hepatic Encephalopathy / etiology
  • Hepatic Encephalopathy / prevention & control*
  • Humans
  • Liver Cirrhosis / surgery*
  • Male
  • Middle Aged
  • Portasystemic Shunt, Transjugular Intrahepatic*
  • Rifaximin / therapeutic use*

Substances

  • Gastrointestinal Agents
  • Rifaximin

Associated data

  • ClinicalTrials.gov/NCT02016196