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Original Investigation
October 4, 2018

Association Between Aspirin Use and Risk of Hepatocellular Carcinoma

Author Affiliations
  • 1Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston
  • 2Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston
  • 3Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston
  • 4Department of Biostatistics and Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, PR China
  • 5Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
  • 6Department of Pediatrics, Karolinska University Hospital, Stockholm, Sweden
  • 7Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
  • 8Columbia University College of Physicians and Surgeons, New York, New York
  • 9National Cancer Centre Singapore, Singapore
  • 10Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
  • 11Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
  • 12Yale University Cancer Center, New Haven, Connecticut
  • 13Dana-Farber Cancer Center, Boston, Massachusetts
  • 14Broad Institute, Boston, Massachusetts
  • 15Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
JAMA Oncol. Published online October 4, 2018. doi:10.1001/jamaoncol.2018.4154
Key Points

Question  What are the associations between aspirin dose and duration of use and the risk of developing hepatocellular carcinoma?

Findings  In this population-based study of 2 nationwide, prospective cohorts of 87 507 men and 45 864 women, self-reported regular use of standard dose (325 mg) aspirin tablets at least 2 or more times per week was associated with a significantly 49% reduced risk of developing hepatocellular carcinoma. The observed benefit of aspirin was both dose and duration dependent, appearing with aspirin use for 5 years or more, at a dose of 1.5 or more standard tablets per week.

Meaning  Use of at least 1.5 standard aspirin tablets per week may represent a feasible strategy for primary prevention against hepatocellular carcinoma; however, potential benefits must be carefully balanced with hazards.


Importance  Prospective data on the risk of hepatocellular carcinoma (HCC) according to dose and duration of aspirin therapy are limited.

Objective  To examine the potential benefits of aspirin use for primary HCC prevention at a range of doses and durations of use within 2 prospective, nationwide populations.

Design, Setting, and Participants  Pooled analysis of 2 prospective US cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. Data were accessed from November 1, 2017, through March 7, 2018. A total of 133 371 health care professionals who reported data on aspirin use, frequency, dosage, and duration of use biennially since 1980 in women and 1986 in men were included. Individuals with a cancer diagnosis at baseline (except nonmelanoma skin cancer) were excluded.

Main Outcomes and Measures  Cox proportional hazards regression models were used to calculate multivariable adjusted hazard ratios (HRs) and 95% CIs for HCC.

Results  Of the 133 371 participants, 87 507 were women and 45 864 were men; in 1996, the median time of follow-up, the mean (SD) age was 62 (8) years for women and 64 (8) years for men. Over more than 26 years of follow-up encompassing 4 232 188 person-years, 108 incident HCC cases (65 women, 43 men) were documented. Compared with nonregular use, regular aspirin use (≥2 standard-dose [325-mg] tablets per week) was associated with reduced HCC risk (adjusted HR, 0.51; 95% CI, 0.34-0.77). This benefit appeared to be dose related: compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 standard-dose tablets per week, 0.51 (95% CI, 0.30-0.86) for more than 1.5 to 5 tablets per week, and 0.49 (95% CI, 0.28-0.96) for more than 5 tablets per week (P for trend = .006). Significantly lower HCC risk was observed with increasing duration (P for trend = .03); this decrease was apparent with use of 1.5 or more standard-dose aspirin tablets per week for 5 or more years (adjusted HR, 0.41; 95% CI, 0.21-0.77). In contrast, use of nonaspirin nonsteroidal anti-inflammatory drugs was not significantly associated with HCC risk (adjusted HR, 1.09; 95% CI, 0.78-1.51).

Conclusions and Relevance  This study suggests that regular, long-term aspirin use is associated with a dose-dependent reduction in HCC risk, which is apparent after 5 or more years of use. Similar associations were not found with nonaspirin NSAIDs. Further research appears to be needed to clarify whether aspirin use represents a feasible strategy for primary prevention against HCC.