CLINICAL QUESTION: Does statin use lower the risk of hepatocellular carcinoma (HCC) and hepatic decompensation in patients with chronic liver disease by mitigating liver fibrosis progression?
BACKGROUND: Metabolic and alcohol-related liver diseases have become the major cause of hepatocellular carcinoma. Experimental studies suggest that statins may prevent hepatocarcinogenesis via anti-inflammatory, antifibrotic, and antioxidant mechanisms, but the association between statin use and incidence of HCC and hepatic decompensation is not fully understood.
STUDY DESIGN: Retrospective cohort study
SETTING: One hospital system, including 10 hospitals, with a research patient data registry of approximately four million patients in the U.S.
SYNOPSIS: Among 16,591 adults aged 40 and over with chronic liver disease (CLD), statin users were compared to the non-users, with the primary outcome as incidence of HCC and the secondary outcome as incidence of hepatic decompensation. Fibrosis was assessed by FIB-4 scores. Over 10 years, statin exposure was linked to lower HCC incidence (3.8% versus 8.0%; 95% CI, –5.3 to –3.1) and hepatic decompensation (10.6% versus 19.5%; CI, 10.6% to –7.3%). Patients with at least 600 cumulative defined daily doses had the lowest incidence of HCC (3.5%) compared with 8% of nonusers (95% CI, –5.6 to –3.2), highlighting a duration-response relationship. Statin users were more likely to transition from high to intermediate (31.8%; 95% CI, 28.0% to 35.9%) or to low (7.0%; 95% CI, 5.2% to 9.6%) FIB-4 score groups, compared with 18.8% (95% CI, 17.2% to 20.6%) and 4.3% (95% CI, 3.5% to 5.2%) of non-users (P < 0.001). Limitations include possible confounding factors such as socioeconomic status, in addition to the inability to account for younger patients and different etiologies of CLD.
BOTTOM LINE: In patients with CLD, statin use, particularly of longer duration, was associated with a reduced risk of HCC and hepatic decompensation, supporting the potential role of statins in HCC prevention through their role in mitigating fibrosis progression.
CITATION: Choi J, 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.
Dr. Xing
Dr. Xing is an assistant clinical professor and a hospitalist at UC San Diego Health in San Diego.