Herbal Medicine Containing Aristolochic Acid and the Risk of Hepatocellular Carcinoma in Patients with Hepatitis C Virus Infection: A Nationwide Population-Based Cohort Study in Taiwan

摘要

Background: The purpose of this study was to investigate the association between the use of herbal medicine containing aristolochic acid (AA) and the risk of hepatocellular carcinoma (HCC) among hepatitis C virus (HCV)-infected patients. Methods and Findings: We conducted a nationwide population-based cohort study on patients older than 18 years who had a diagnosis of HCV infection between January $11997 and December 3$12010. A total of 223,467 HCV-infected patients were identified by using the National Health Insurance Research Database in Taiwan. The use of herbal medicine containing AA was identified between 1997 and 2003 and had visited traditional Chinese medicine clinics before one year before the diagnosis of HCC or the censor dates. Each patient was individually tracked from 1997 to 2013 to identify incident cases of HCC since 1999. There were 25,502 HCCs during the follow-up period of 3,052,132 person-years and the overall incidence rate was 835.5 HCCs per 100,000 person-years. The adjusted hazard ratios (HRs) were 1.21 (95% confidence interval [CI], 1.18 to 1.24), 1.48 (95% CI, 1.37 to 1.59), 1.50 (95% CI, 1.34 to 1.68), and 1.88 (95% CI, 1.61 to 2.19) for estimated AA of 1 to 250, 251 to 500, 501 to 1,000, and more than 1,000 mg, respectively, relative to no AA exposure. Conclusions: Our study suggests that AA exposure in association with HCV plays an important role in the carcinogenesis of HCC.