Statin exposure is associated with reduced development of acute on chronic liver failure in a veterans affairs cohort.

There is a need to identify therapies that may prevent development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis. This study sought to evaluate the association between statin exposure and the risk of developing ACLF in a large national cohort of patients with cirrhosis.We performed a retrospective cohort study of patients diagnosed with cirrhosis within the Veterans Health Administration from 2008 and 2018. Patients were stratified into three groups based on statin exposure (statin naïve, existing statin user, and new statin initiator). Cox proportional hazards regression models with inverse probability treatment weighting and marginal structural models were utilized to comprehensively address potential confounding in estimating the association between time-updated statin exposure and first occurrence of high-grade ACLF.The cohort included 84,963 patients, of which 26.9% were on a statin at baseline. A total of 8,558 (10.1%) patients with cirrhosis were hospitalized with high-grade ACLF over median follow-up time of 51.6 months (IQR 27.5, 81.4). Time-updated statin use was associated with a significant reduction in the hazard of developing ACLF (HR 0.62, 95% CI 0.59-0.65, p<0.001). Increasing doses of statin were associated with progressively reduced hazard of developing ACLF (HR 0.75, 95% CI 0.66-0.86, p<0.001 for <20mg vs. 0mg of time-updated statin exposure, in simvastatin equivalents; HR 0.61, 95%, CI 0.58-0.64, p<0.001 for >20mg vs. 0mg statin exposure). Furthermore, every additional 5 months of statin exposure was associated with a 9% reduced hazard of high-grade ACLF (HR 0.91, 95% CI 0.90-0.92, p<0.001).In this large, retrospective cohort study in patients with cirrhosis, statin use was significantly associated with reduced development of high-grade ACLF.Statin therapy has been shown to have numerous beneficial effects in patients with chronic liver disease. This study demonstrated a strong association between statin therapy and a reduced risk for the development of acute-on-chronic liver failure in patients with cirrhosis. The results of this study support the promising role that statins may play in future prevention of acute-on-chronic liver failure in patients with cirrhosis.