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Original Investigation
March 18, 2019

Association of Daily Aspirin Therapy With Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B

Author Affiliations
  • 1Division of Gastroenterology & Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan
  • 2Department of Medicine, Chung Shan Medical University, Taichung, Taiwan
  • 3Division of Gastroenterology and Hepatology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan
  • 4School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan
  • 5Division of Gastroenterology and Hepatology, E-Da Hospital, Kaohsiung, Taiwan
  • 6Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan
  • 7Division of Translational Medicine and Excellence Cancer Research Center, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
  • 8Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan
  • 9Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
  • 10Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
  • 11College of Public Health and Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
  • 12National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan
JAMA Intern Med. 2019;179(5):633-640. doi:10.1001/jamainternmed.2018.8342
Key Points

Question  Is daily aspirin therapy associated with risk of hepatocellular carcinoma in patients with chronic hepatitis B?

Findings  In this Taiwan nationwide cohort study of 10 615 patients with chronic hepatitis B, there was a statistically significant 29% risk reduction of hepatocellular carcinoma in 2123 patients who received daily aspirin compared with the matched 8492 controls.

Meaning  Daily aspirin therapy may be of help to further improve the chemoprevention of hepatitis B virus–related hepatocellular carcinoma.


Importance  Antiviral therapy cannot erase hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B, and it is not indicated for most hepatitis B virus (HBV) carriers. Another effective way of reducing HCC risk needs to be developed. Aspirin may prevent cancer development, but clinical evidence in patients with HBV-related HCC remains limited.

Objective  To investigate the association of daily aspirin therapy with HBV-related HCC risk.

Design, Setting, and Participants  In this Taiwan nationwide cohort study, we screened 204 507 patients with chronic hepatitis B for the period January 1, 1997, to December 31, 2012. After excluding patients with confounding conditions, 2123 patients who continuously received daily aspirin for 90 or more days (treated group) were randomly matched 1:4 with 8492 patients who had never received antiplatelet therapy (untreated group) by means of propensity scores, consisting of the follow-up index date, baseline characteristics, and potentially chemopreventive drug use during follow-up. Data were analyzed from August 1 to November 30, 2018.

Exposures  Daily aspirin therapy during the study period.

Main Outcomes and Measures  Both cumulative incidence of and hazard ratios (HRs) for HCC development were analyzed after adjusting patient mortality as a competing risk event.

Results  Of the 10 615 patients included in the analysis, 7690 (72.4%) were men; mean (SD) age was 58.8 (11.8) years. The cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group in 5 years (5.20%; 95% CI, 4.11%-6.29% vs 7.87%; 95% CI, 7.15%-8.60%; P < .001). In the multivariable regression analysis, aspirin therapy was independently associated with a reduced HCC risk (HR, 0.71; 95% CI, 0.58-0.86; P < .001). Sensitivity subgroup analyses also verified this association (all HRs <1.0). In addition, older age (HR, 1.01 per year; 95% CI, 1.00-1.02), male sex (HR, 1.75; 95% CI, 1.43-2.14), and cirrhosis (HR, 2.89; 95% CI, 2.45-3.40) were independently associated with an increased HCC risk, but nucleos(t)ide analogue (HR, 0.54; 95% CI, 0.41-0.71) or statin (HR, 0.62; 95% CI, 0.42-0.90) use was correlated with a decreased HCC risk.

Conclusions and Relevance  Daily aspirin therapy may be associated with a reduced risk of HBV-related HCC.

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