Author information

¹Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, Seoul, 06351, South Korea.

²Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-Gu, Seoul, 06351, South Korea.

³Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea.

⁴Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Korea.

⁵Departments of Epidemiology and Medicine, Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

⁶Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-Gu, Seoul, 06351, South Korea. jcho@skku.edu.

⁷Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea. jcho@skku.edu.

⁸Departments of Epidemiology and Medicine, Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA. jcho@skku.edu.

⁹Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, Seoul, 06351, South Korea. gy.gwak@samsung.com.

^#Contributed equally.

Abstract

Background: No randomized controlled trials have been completed to see whether statin can decrease hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. We used large-scale, population-based, observational data to emulate a target trial with two groups, statin user and statin non-user.

Methods: Among 1,379,708 nonunique individuals from the Korean National Health Insurance Service data, 2,915 CHB patients with serum cholesterol level of 200 mg/dL or higher who started statin therapy and 8,525 propensity-score matched CHB patients with serum cholesterol level of 200 mg/dL or higher who did not start statin therapy were analyzed for the development of HCC. In addition, liver cancer or liver-related mortality and all-cause mortality were assessed.

Results: During follow-up, 207 participants developed HCC. Incidence rate of HCC was 0.2 per 1,000 person-years in the statin user group and 0.3 per 1,000 person-years in the statin non-user group. Fully adjusted hazard ratio (HR) for incident HCC comparing statin user group to statin nonuser group was 0.56 (95% confidence interval [CI]: 0.39 to 0.80). The association between statin use and decreased HCC risk was consistent in all subgroups analyzed. Fully adjusted HR comparing statin user to statin nonuser was 0.59 (95% CI: 0.35 to 0.99) for liver cancer or liver-related mortality and 0.93 (95% CI: 0.78 to 1.11) for all-cause mortality.

Conclusions: Statin might have a benefit for preventing HCC in CHB patients with elevated cholesterol levels. Statin should be actively considered for CHB patients with dyslipidemia.