Association of aspirin and statin use with the risk of liver cancer in chronic hepatitis B: A nationwide population-based study
Won-Mook Choi and Hyo Jeong Kim contributed equally to this work.
Handling Editor: Pierre Nahon
Funding information
This study was supported by grants from the National Evidence-based Healthcare Collaborating Agency (NECA, No. NS-19-004) and National Research Foundation of Korea (NRF) funded by the Korea government (MSIT, No. 2017R1A2B4011233); Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HI19C0790); and the Technology Innovation Program (10079271) funded by the Ministry of Trade, Industry & Energy (MOTIE) of the Republic of Korea. The funding sources had no role in the design and conduct of the study; collection, management, analysis and interpretation of data; preparation, review or approval of the manuscript; and the decision to submit the manuscript for publication.
Abstract
Background & Aims
Aspirin and statins have been suggested to prevent hepatocellular carcinoma (HCC). However, the combined effects of aspirin and statins on HCC risk in patients with chronic hepatitis B (CHB) are not clear.
Methods
A nationwide nested case-control study was performed with data from the National Health Insurance Service gathered between 2005 and 2015 in Korea. In a cohort of 538,135 treatment-naïve, non-cirrhotic patients with CHB, 6,539 HCC cases were matched to 26,156 controls and were analysed by conditional logistic regression. Separate historical cohort studies for each drug were analysed by time-dependent Cox regression as a sensitivity analysis.
Results
In the nested case-control study, statins (OR 0.34; 95% CI 0.32-0.37) and aspirin (OR 0.92; 95% CI 0.85-0.99) were significantly associated with a HCC risk reduction. However, dose-dependent risk reduction was observed only with statins. By sensitivity analysis in the historical cohorts, statin users (n = 244,455; HR 0.67; 95% CI 0.66-0.68) and aspirin users (n = 288,777; HR 0.81; 95% CI 0.80-0.82) had significantly lower HCC risk. In the drug-stratified analyses, statins were associated with significantly reduced risk of HCC regardless of aspirin, whereas aspirin did not show such associations.
Conclusions
In this nationwide population-based study of patients with CHB, statin use was consistently associated with a significant and dose-dependent reduction in HCC risk. In contrast, the association between aspirin use and HCC risk reduction was not dose-dependent and was suggested to be confounded by statins.
CONFLICT OF INTEREST
Y-SL is an advisory board member of Bayer Healthcare and Gilead Sciences and receives investigator-initiated research funding from Bayer Healthcare and Gilead Sciences; the remaining authors report no other relationships or activities that could appear to have influenced the submitted work.
