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

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.

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

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.

Use of an α-Glucosidase Inhibitor and the Risk of Colorectal Cancer in Patients With Diabetes: A Nationwide, Population-Based Cohort Study.

OBJECTIVE: Acarbose, an α-glucosidase inhibitor, has been shown to have antineoplastic effects on colorectal cancer in biomarker studies. We assessed the association between acarbose use in patients with diabetes and incident colorectal cancer. RESEARCH DESIGN AND METHODS: We conducted a nationwide, population-based study using a large cohort with diabetes in the Taiwan National Health Insurance Research Database. Patients with newly diagnosed diabetes (n = 1,343,484) were enrolled between 1998 and 2010. One control subject not using acarbose was randomly selected for each subject using acarbose after matching for age, sex, diabetes onset, and comorbidities. Cox proportional hazards regression with a competing risks analysis was used to calculate the hazard ratios (HRs) and 95% CIs for the association between acarbose use and incident colorectal cancer for each eligible case-control pair (n = 199,296). RESULTS: There were 1,332 incident cases of colorectal cancer in the cohort with diabetes during the follow-up period of 1,487,136 person-years. The overall incidence rate was 89.6 cases per 100,000 person-years. Patients treated with acarbose had a 27% reduction in the risk of colorectal cancer compared with control subjects. The adjusted HRs were 0.73 (95% CI 0.63-0.83), 0.69 (0.59-0.82), and 0.46 (0.37-0.58) for patients using >0 to <90, 90 to 364, and ≥365 cumulative defined daily doses of acarbose, respectively, compared with subjects who did not use acarbose (P for trend < 0.001). CONCLUSIONS: Acarbose use reduced the risk of incident colorectal cancer in patients with diabetes in a dose-dependent manner.