Statins and Improved Long-Term Liver Outcomes in PBC, With Jonggi Choi, MD, PhD

Statins are widely recognized as cholesterol-lowering agents, but over the past decade, accumulating evidence has suggested their benefits may extend beyond lipid management.

A new study published in Hepatology highlights a reduced risk of hepatic decompensation and major liver events in patients with primary biliary cholangitis (PBC) taking statins, supporting a potential protective effect in this population.

“Several large observational studies have suggested that statins may slow liver fibrosis, reduce complications related to portal hypertension, and even lower the risk of liver cancer,” Jonggi Choi, MD, PhD, an associate professor at Asan Medical Center, University of Ulsan College of Medicine, and visiting scholar at Mass General Hospital, told HCPLive. “About a year ago, our group also published a large case study in JAMA Internal Medicine showing that statin use was associated with improved outcomes in patients with overall chronic liver disease, which further raised interest in their potential liver protective effects. However, when it comes to PBC, the evidence has been much more limited.”

He noted that PBC is a rare autoimmune cholestatic liver disease characterized by chronic inflammation and progressive destruction of the small bile ducts, ultimately leading to cirrhosis if left untreated. Most prior studies in PBC, he explained, focused on short-term laboratory changes rather than clinically meaningful long-term outcomes like liver failure, transplantation, or cancer. As a result, whether statins influence the long-term course of PBC has remained unclear.

Because randomized controlled trials are particularly challenging in rare diseases like PBC, investigators used a target trial emulation approach with real-world data. As Choi described, this method structures observational data to closely mimic a randomized clinical trial, helping to minimize common biases such as immortal time bias.

Using 2 large, independent electronic health record databases from Mass General Brigham and Asan Medical Center, investigators identified statin initiation on a month-by-month basis. In each monthly trial, statin initiators were matched in a 1:2 ratio to non-users using propensity score matching.

The primary outcome was hepatic decompensation while 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. During 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 additionally associated with a reduced risk of MALO (HR, 0.58; 95% CI: 0.38–0.89).

Importantly, Choi noted 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, indicating that results were consistent across different groups.

Editors’ Note: Choi reports relevant disclosures with Gilead.

References

1. Choi J, Xu J, Nguyen VH, et al. Association between statin use and hepatic decompensation in patients with primary biliary cholangitis: A target trial emulation study. Hepatology. doi:10.1097/HEP.0000000000001701

2. Choi J, Nguyen VH, Przybyszewski E, et al. Statin Use and Risk of Hepatocellular Carcinoma and Liver Fibrosis in Chronic Liver Disease. JAMA Intern Med. 2025;185(5):522–530. doi:10.1001/jamainternmed.2025.0115