Rifaximin has the potential to prevent complications of cirrhosis

Steven L Flamm, Kevin D Mullen, Zeev Heimanson, Arun J Sanyal, Steven L Flamm, Kevin D Mullen, Zeev Heimanson, Arun J Sanyal

Abstract

Background: Cirrhosis-related complications are associated with poor prognosis. With our analyses, we examined the potential benefit of rifaximin in reducing the risk of developing cirrhosis-related complications.

Methods: Adults with cirrhosis and hepatic encephalopathy (HE) in remission were randomly assigned to receive rifaximin 550 mg twice daily or placebo for 6 months with concomitant lactulose permitted. Post hoc analyses examined time to cirrhosis-related complications (HE, spontaneous bacterial peritonitis (SBP), variceal bleeding, acute kidney injury/hepatorenal syndrome). Subgroup analyses evaluated efficacy for select baseline disease characteristics.

Results: Of patients receiving rifaximin (n = 140) and placebo (n = 159), 53.6% and 49.1%, respectively, had baseline Model for End-Stage Liver Disease (MELD) score ⩾ 12 and international normalized ratio (INR) ⩾ 1.2. Baseline ascites was observed in 36.4% (rifaximin) and 34.6% (placebo) of patients. In patients with MELD score ⩾ 12 and INR ⩾ 1.2, rifaximin reduced the relative risk (RR) of any first complication experienced during trial by 59% [hazard ratio (HR) = 0.41, 95% confidence interval (CI): 0.25-0.67; p < 0.001] versus placebo. For patients with baseline ascites, rifaximin reduced the RR of any first complication experienced during trial by 42% versus placebo (HR = 0.58, 95% CI: 0.34-1.0; p = 0.045). For some subgroups, there was a decrease in RR of complications of SBP, variceal bleeding, and acute kidney injury/hepatorenal syndrome with rifaximin versus placebo, although there were few events reported in the study.

Conclusion: Rifaximin may reduce the incidence of cirrhosis-related complications and the recurrence of overt HE.[ClinicalTrials.gov identifier: NCT00298038.].

Keywords: antibiotic; cirrhosis; decompensation; hepatic encephalopathy; rifaximin.

Conflict of interest statement

Conflict of interest statement: SL Flamm is a consultant and has served on the speakers’ bureau for AbbVie, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck & Co., Inc., and Salix Pharmaceuticals; and has received research support from AbbVie, Gilead Sciences, Inc., and Intercept Pharmaceuticals, Inc. KD Mullen has served as a consultant for Salix Pharmaceuticals and Norgine. Z Heimanson is an employee of Salix Pharmaceuticals. AJ Sanyal has stock options in Genfit and is the president of Sanyal Biotechnology. He has served as a consultant to AbbVie, AstraZeneca, Bristol-Myers Squibb Company, DURECT Corporation, Enanta Pharmaceuticals, Inc., Galmed Pharmaceuticals Ltd., Genfit, Gilead Sciences, Inc., Ikaria, Immuron, Intercept Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Nitto Denko Corporation, Novartis, Salix Pharmaceuticals, and Zafgen.

Figures

Figure 1.
Figure 1.
Time to a first complication of cirrhosis experienced during the trial by treatment group and baseline disease severity. (a) All complications of cirrhosis in patients with MELD score ⩾ 12 and INR ⩾1.2; (b) non-HE complications of cirrhosis in patients with MELD score ⩾ 12 and INR ⩾ 1.2; and (c) all complications of cirrhosis in patients with MELD score

Figure 2.

Time to a first complication…

Figure 2.

Time to a first complication of cirrhosis experienced during the trial by treatment…

Figure 2.
Time to a first complication of cirrhosis experienced during the trial by treatment group. All complications of cirrhosis according to (a) presence or (b) absence of ascites at baseline; and non-HE complications of cirrhosis according to (c) presence or (d) absence of ascites at baseline. BID, twice daily; CI, confidence interval; HE, hepatic encephalopathy; HR, hazard ratio.
Figure 2.
Figure 2.
Time to a first complication of cirrhosis experienced during the trial by treatment group. All complications of cirrhosis according to (a) presence or (b) absence of ascites at baseline; and non-HE complications of cirrhosis according to (c) presence or (d) absence of ascites at baseline. BID, twice daily; CI, confidence interval; HE, hepatic encephalopathy; HR, hazard ratio.

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