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.

The present investigation was designed to explore the risk of stomach cancer by oral intake of talc powder without asbestos. We conducted a population-based cohort study on a randomly sampled cohort from Taiwan’s health insurance database, with population of 1,000,000. The study participants were followed up through 2013. The outcome event of interest was the diagnosis of stomach cancer. The exposure of interest was the prescription of talc powder. Cox regression analyses were performed respectively. There were 584,077 persons without talc exposure and 21,575 talc users, 1849 diagnosed with stomach cancer. Persons with exposure of talc had a higher hazard ratio of stomach cancer (adjusted hazard ratio, 2.13; 95% confidence interval (CI), 1.54–2.94; p < 0.001). Classification by cumulative exposure of talc yielded adjusted hazard ratios of stomach cancer of 1.58 (95% CI, 0.79–3.17; p = 0.19) and 2.30 (95% CI, 1.48–3.57; p < 0.001) among persons with high (>21 g) and medium (6–21 g) exposure of talc, as compared to the low-exposure counterparts. Our data demonstrated positive association between increased risk of stomach cancer and oral intake of talc without asbestos. Despite the absence of dose-response effect, there might be a link between stomach cancer and talc.

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 followup 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 personyears, we identified 25,502 PLC cases; this corresponded to an overall incidence rate of 835.5 PLCs per 100,000 personyears. 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.