Herbal Medicine Containing Aristolochic Acid and the Risk of Primary Liver Cancer in Patients with Hepatitis C Virus Infection

Cancer Epidemiol Biomarkers Prev. 2019 Nov;28(11):1876-1883. doi: 10.1158/1055-9965.EPI-19-0023. Epub 2019 Aug 13.


Background: We investigated the association between taking herbal medicine (HM) containing aristolochic acid (AA) and the risk of primary liver cancer (PLC) among patients with hepatitis C virus (HCV) infection.

Methods: This is a prospective study for the long-term follow-up of a nationwide population-based cohort of patients ages 18 years or older diagnosed with HCV infection during 1997 to 2010. A total of 223,467 HCV-infected patients were identified using the National Health Insurance Research Database in Taiwan. The use of HM containing AA was evaluated among patients who had visited traditional Chinese medicine clinics beginning from 1997 to 1 year prior to the diagnosis of PLC or dates censored (2003). We tracked each individual patient from 1997 to 2013 to identify incident cases of PLC since 1999.

Results: During the follow-up period of 3,052,132 person-years, we identified 25,502 PLC cases; this corresponded to an overall incidence rate of 835.5 PLCs per 100,000 person-years. The adjusted HRs were 1.21 [95% confidence interval (CI), 1.18-1.24], 1.48 (95% CI, 1.37-1.59), 1.50 (95% CI, 1.34-1.68), and 1.88 (95% CI, 1.61-2.19) for estimated AA usage groups: 1 to 250, 251 to 500, 501 to 1,000, and more than 1,000 mg, respectively, relative to no AA exposure (reference group).

Conclusions: The current findings suggest that among HCV-positive patients, increasing exposure to AA poses an increased risk of acquiring PLC.

Impact: AA may increase the risk of PLC in HCV-positive populations.

MeSH terms

  • Aristolochic Acids / adverse effects*
  • Carcinogens / chemistry*
  • Female
  • Hepacivirus / pathogenicity*
  • Hepatitis C / complications*
  • Herbal Medicine / methods*
  • Humans
  • Liver Neoplasms / chemically induced*
  • Male
  • Prospective Studies
  • Risk Factors


  • Aristolochic Acids
  • Carcinogens
  • aristolochic acid I