Send to

Choose Destination
Int J Cancer. 2018 Oct 1;143(7):1578-1587. doi: 10.1002/ijc.31544. Epub 2018 May 7.

Herbal medicine containing aristolochic acid and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection.

Author information

Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi County, Taiwan.
Graduate Institute of Data Science, Taipei Medical University, Taipei, Taiwan.
Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi County, Taiwan.
Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan.
School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Division of Occupational Medicine, Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Department of Statistics, Feng Chia University, Taichung, Taiwan.
Department of Public Health, National Taiwan University College of Public Health, Taipei, Taiwan.
Department of Public Health, China Medical University, Taichung, Taiwan.
Department of Environmental and Occupational Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

Erratum in


It was suspected that aristolochic acid-induced mutations may be associated with hepatitis B virus (HBV), playing an important role in liver carcinogenesis. The purpose of this study was to investigate the association between the use of Chinese herbs containing aristolochic acid and the risk of hepatocellular carcinoma (HCC) among HBV-infected patients. We conducted a retrospective, population-based, cohort study on patients older than 18 years who had a diagnosis of HBV infection between January 1, 1997 and December 31, 2010 and had visited traditional Chinese medicine clinics before one year before the diagnosis of HCC or the censor dates. A total of 802,642 HBV-infected patients were identified by using the National Health Insurance Research Database in Taiwan. The use of Chinese herbal products containing aristolochic acid was identified between 1997 and 2003. Each patient was individually tracked from 1997 to 2013 to identify incident cases of HCC since 1999. There were 33,982 HCCs during the follow-up period of 11,643,790 person-years and the overall incidence rate was 291.8 HCCs per 100,000 person-years. The adjusted hazard ratios (HRs) were 1.13 (95% confidence interval [CI], 1.11-1.16), 1.21 (95% CI, 1.13-1.29), 1.37 (95% CI, 1.24-1.50) and 1.61 (95% CI, 1.40-1.84) for estimated aristolochic acid of 1-250, 251-500, 501-1,000 and more than 1,000 mg, respectively, relative to no aristolochic acid exposure. Our study found a significant dose-response relationship between the consumption of aristolochic acid and HCC in patients with HBV infection, suggesting that aristolochic acid which may be associated with HBV plays an important role in the pathogenesis of HCC.


aristolochic acid; hepatitis B virus infection; hepatocellular carcinoma; herbal medicine

Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center