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



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.


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


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.



Daily aspirin therapy during the study period.



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



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.



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


Lee TY1,2, Hsu YC3,4,5,6, Tseng HC7, Yu SH1, Lin JT4,8, Wu MS9, Wu CY7,10,11,12.


JAMA Intern Med. 2019 Mar 18. doi: 10.1001/jamainternmed.2018.8342. [Epub ahead of print]

Author Information

  1. Division of Gastroenterology & Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan.

  2. Department of Medicine, Chung Shan Medical University, Taichung, Taiwan.

  3. Division of Gastroenterology and Hepatology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan.

  4. School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan.

  5. Division of Gastroenterology and Hepatology, E-Da Hospital, Kaohsiung, Taiwan.

  6. Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan.

  7. Division of Translational Medicine and Excellence Cancer Research Center, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.

  8. Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.

  9. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

  10. Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

  11. College of Public Health and Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.

  12. National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.

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