Simvastatin and rifaximin in patients with decompensated cirrhosis: Still a place for LIVER HOPE?

Abstract

Section snippets

Background and context

In patients with cirrhosis, prognosis is primarily determined by the development of portal hypertension-related decompensation.¹ Acute-on-chronic liver failure (ACLF) defined by the concomitant occurrence of decompensation and organ failure, is associated with worse prognosis than decompensation alone.² Once decompensation occurs, clinical management should address both the current decompensation event(s) and the prevention of further decompensation, as defined by Baveno VII.³ Both

Objectives, methods and findings

In the LIVERHOPE phase III trial,⁹ patients with decompensated cirrhosis were assigned to receive simvastatin 20 mg/day and rifaximin 1,200 mg/day (n = 117), or placebo (n = 120) for 12 months, stratified according to Child-Pugh class. The primary endpoint was incident ACLF, and secondary outcomes included transplant or death and a composite endpoint of complications of cirrhosis (ascites, hepatic encephalopathy, acute variceal bleeding, acute kidney injury, and infection). Overall, there was

Significance of findings

This large multicenter international randomized controlled trial (RCT) unfortunately failed to demonstrate any efficacy of the combination of simvastatin 20 mg/day and rifaximin 1,200 mg/day for the prevention of ACLF and further decompensation in patients with decompensated cirrhosis. The rationale for the use of simvastatin relied on its role in reducing portal hypertension, and a survival benefit in patients with a history of acute variceal bleeding.¹⁰ However, the baseline characteristics

Financial support

The authors did not receive any financial support to produce this manuscript.

Conflict of interest

Gore, Abbvie, Gilead.Please refer to the accompanying ICMJE disclosure forms for further details.