Non-Selective Beta-Blockers and Risk of Sepsis in Patients with Cirrhosis and Ascites: Results from a Large Observational Study

Abstract

Background and Aims

Previous studies have not been able to determine whether non-selective beta-blockers (NSBB) reduce the risk of sepsis in cirrhosis. We aimed to examine this question with data from 1198 patients with cirrhosis and ascites included in clinical studies of satavaptan, a vasopressin receptor antagonist with no effect on infection risk.

Methods

Risk of sepsis was estimated for NSBB users vs nonusers. Patients were examined every four weeks, or in relation to hospitalization, for the one-year duration of the trials. We computed the cumulative risk of sepsis for patients who did vs did not use NSBB at baseline. We used Cox regression to compare hazard rates of sepsis between current users and nonusers, accounting for changes in NSBB use over time. We adjusted for patient sex and age, MELD-Na score, albumin, use of antibiotics, use of proton pump inhibitors, cirrhosis etiology, history of variceal bleeding or SBP, severity of ascites and HE, HCC, other cancers, and diabetes, while stratifying on geographical region.

Results

Of the 1198 patients, 54% used NSBB at some time. There were 56 sepsis episodes. The 1-year risk of sepsis was reduced to 5.7% (95% confidence interval [CI] 2.8–8.6) in baseline NSBB users vs 11.6% (95% CI 7.0–15.9) in baseline nonusers. The hazard ratio of sepsis for current NSBB users vs current nonusers was reduced to 0.5 (95% CI 0.3–0.8) and after adjustment to 0.7 (95% CI 0.4–1.3).

Conclusion

NSBB use may reduce the risk of sepsis in patients with cirrhosis and ascites, but the precision of the estimate was limited by the number of episodes of sepsis.

Keywords:

• non-selective beta-blockers
• NSBB
• infection
• decompensated
• time-dependent
• treatment

Abbreviations

NSBB, non-selective beta-blocker; SBP, spontaneous bacterial peritonitis; TIPS, transjugular intrahepatic portosystemic shunt; HE, hepatic encephalopathy; INR, international normalized ratio; HCC, hepatocellular carcinoma; MELD, model for end-stage liver disease; PPI, proton pump inhibitor; HR, hazard rate ratio; GI, gastrointestinal; SOFA-score, Sequential Organ Failure Assessment score; HVPG, hepatic venous pressure gradient.

Data Sharing Statement

Data are available upon reasonable request.

Ethics and Consent Statement

This project, where data from an ethical committee-approved project were used, did not require a new approval from an ethics committee, according to Danish law. All data used complied with relevant data protection and privacy regulations.

Acknowledgment

The abstract of this paper was presented as an oral presentation at ‘AASLD: The Liver Meeting 2020’ with interim findings and was included in ‘The Best of The Liver Meeting’. The abstract was published in ‘Oral Abstracts’ in ‘Hepatology’: https://doi.org/10.1002/hep.31578.

Disclosure

Hugh Watson is an employee of Evotec and holds shares in Sanofi. No other conflicts of interest to declare.

Additional information

Funding

The funding sources had no involvement in the writing of the article.