Association between statin use and hepatic decompensation in patients with primary biliary cholangitis: A target trial emulation study

BACKGROUND AND AIMS: Statins have been investigated for their potential to reduce liver-related complications in chronic liver diseases, but evidence in primary biliary cholangitis (PBC) remains limited. This study aimed to assess the association between statin use and the risk of hepatic decompensation using a target trial emulation (TTE) design. APPROACH AND RESULTS: We performed a sequential TTE using 2 electronic health record databases: Mass General Brigham (MGB, Boston, USA) and Asan Medical Center (AMC, Seoul, Korea). Adults diagnosed with PBC between 2001 and 2024 were eligible. Statin use was defined as a cumulative duration of ≥90 days. In each monthly trial, statin initiators were matched 1:2 to non-users using propensity score matching. The primary outcome was hepatic decompensation; the secondary outcome was a composite major adverse liver outcome (MALO), including decompensation, hepatocellular carcinoma, and liver transplantation. Among 2889 eligible patients, 443 statin users were matched to 886 non-users. Over a median follow-up of 3.8 years, hepatic decompensation occurred in 24 statin users (5.4%) and in 67 non-users (7.6%) [hazard ratio (HR), 0.61; 95% confidence interval (CI): 0.38-0.97]. Statin use was also associated with a reduced risk of MALO (HR, 0.58; 95% CI: 0.38-0.89). Sensitivity analyses stratified by data source (MGB, HR 0.65; AMC, HR 0.60) and cirrhosis status (HR 0.70 for cirrhosis; HR 0.57 for without) showed similar directional trends. CONCLUSIONS: Statin use was consistently associated with a lower risk of hepatic decompensation and major liver events in patients with PBC, supporting a potential protective effect.