Association between statin exposure and short-term mortality in patients with high-grade acute-on-chronic liver failure

Background & Aims: Acute-on-chronic liver failure (ACLF) carries a high short-term mortality for patients with cirrhosis. Prior literature suggests that statin exposure may reduce the likelihood of ACLF events. However, it is unclear if statin exposure is associated with ACLF-related mortality. This study sought to determine the association between statin use and short-term mortality among patients hospitalised with ACLF. Methods: This was a retrospective cohort study of Veterans Health Administration (VHA) patients diagnosed with cirrhosis between 2008 and 2021 and hospitalised with high-grade (2 or 3) ACLF. Patients were stratified into those with and without continuous statin exposure for at least 90 days prior to hospitalisation. Multivariable logistic regression models were created to determine the adjusted association between statin exposure and 28-day and 90-day mortality. Categorical statin dose exposure, converted to simvastatin equivalents, was also explored. Results: A total of 11,731 patients with cirrhosis hospitalised with Grade 2 or 3 ACLF were included in the analytic cohort, 26% of whom had statin exposure. In adjusted logistic regression models, statin use was associated with 18% lower odds of ACLFrelated 28-day mortality (odds ratio [OR] 0.82, 95% CI 0.73-0.93, p = 0.001) and 24% lower odds of 90-day mortality (OR 0.76, 95% CI 0.68-0.86, p <0.001). Increasing statin dose exposure was also associated with further reductions in 90-day mortality (e.g. OR 0.81, 95% CI 0.70-0.93 for 10-40 mg vs. 0 mg and OR 0.72, 95% CI 0.60-0.87 for 80 mg vs. 0 mg, p <0.001). Conclusions: In this large, retrospective cohort study, statin exposure before high-grade ACLF hospitalisation was associated with reduced odds of 28-day and 90-day mortality in patients with cirrhosis. A statin dose-dependent reduction in 90-day ACLF-related mortality was also observed. Impact and Implications: Statins have been identified as a class of medications with potential beneficial effects for patients with cirrhosis. In this large, retrospective cohort study of patients with cirrhosis who seek care at the Veterans Health Administration, statin use was associated with a decrease in short term (28-day and 90-day) mortality as a result of acute-on chronic liver failure. Future prospective studies are needed to further clarify the relative safety and efficacy of statin therapy in reducing morbidity and mortality associated with acute-on-chronic liver failure in patients with cirrhosis. & COPY; 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).