Daily aspirin associated with a reduced risk of hepatocellular carcinoma in patients with non-alcoholic fatty liver disease: a population-based cohort study

Teng-Yu Lee; Yao-Chun Hsu; Hsiu J Ho; Jaw-Town Lin; Yi-Ju Chen; Chun-Ying Wu

doi:10.1016/j.eclinm.2023.102065

Daily aspirin associated with a reduced risk of hepatocellular carcinoma in patients with non-alcoholic fatty liver disease: a population-based cohort study

EClinicalMedicine. 2023 Jun 29:61:102065. doi: 10.1016/j.eclinm.2023.102065. eCollection 2023 Jul.

Authors

Teng-Yu Lee^{1

2}, Yao-Chun Hsu^{3

4

5

6}, Hsiu J Ho⁶, Jaw-Town Lin³, Yi-Ju Chen^{6

7

8

9}, Chun-Ying Wu^{6

9

10

11

12}

Affiliations

¹ Division of Gastroenterology & Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan.
² School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
³ Division of Gastroenterology and Hepatology, E-Da Hospital, Kaohsiung, Taiwan.
⁴ School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
⁵ Division of Gastroenterology and Hepatology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan.
⁶ Institute of Biomedical Informatics, Health Innovation Center, and Microbiota Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁷ Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan.
⁸ Department of Post Baccalaureate Medicine, National Chung Hsing University, Taichung, Taiwan.
⁹ Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
¹⁰ Division of Translational Medicine, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
¹¹ College of Public Health, China Medical University, Taichung, Taiwan.
¹² National Institute of Cancer Research and Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.

Abstract

Background: Emerging laboratory and animal studies suggest that aspirin may prevent non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC), however clinical evidence remains lacking.

Methods: Using Taiwan's National Health Insurance Research Database, we screened 145,212 NAFLD patients from 1997 through 2011. After excluding any confounding conditions, 33,484 patients who continuously received a daily dose of aspirin for 90 days or more (treated group), along with 55,543 patients who had not received antiplatelet therapy (untreated group), were respectively recruited. Inverse probability of treatment weighting using the propensity score was applied to balance the baseline characteristics. Cumulative incidence of, and hazard ratio (HR) for HCC occurrence were analyzed after adjusting competing events. The high-risk patients, who were defined as age ≥ 55 years & elevated serum alanine aminotransferase, were further analyzed.

Findings: The 10-year cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group (0.25% [95% CI, 0.19-0.32%] vs. 0.67% [95% CI, 0.54-0.81%]; P < 0.001). Aspirin therapy was significantly associated with a reduced HCC risk (adjusted HR [aHR] 0.48 [95% CI, 0.37-0.63]; P < 0.001). In the high-risk patients, the 10-year cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group (3.59% [95% CI, 2.99-4.19%] vs. 6.54% [95% CI, 5.65-7.42%]; P < 0.001). Aspirin therapy remained associated with a reduced HCC risk (aHR 0.63 [95% CI, 0.53-0.76]; P < 0.001). Subgroup sensitivity analyses verified this significant association in nearly all subgroups. In the time-varying model amongst aspirin users, HCC risk was significantly lower through the use of aspirin for ≥ 3 years (aHR 0.64 [95% CI, 0.44-0.91]; P = 0.013), when compared with short-term use (< 1 year).

Interpretation: Daily aspirin therapy is significantly associated with a reduced HCC risk in NAFLD patients.

Funding: Ministry of Science and Technology, Ministry of Health and Welfare, and Taichung Veterans General Hospital, Taiwan.

Keywords: Antiplatelet; Chemoprevention; Liver cancer; Prevention.