8 years post-marketing surveillance between Asari Radix and hepatocellular carcinoma: Nationwide population-based evidence against an association.

Asari Radix (Xixin, Asarum heterotropoides Fr. Schmidt var. mandshuricum Kitag., Asarum sieboldii Miq., or Asarum sieboldii Miq. var. seoulense Nakai, Asarum spp.) is the only herbal medicine containing aristolochic acid that can be used in medical practice. However, scientific evidence regarding its safe use in relation to hepatocellular carcinoma (HCC) is lacking.The aim of this study was to use post-marketing surveillance to provide a scientific understanding of the relationship between Asari Radix and the development of HCC and suggest the maximum allowable amount of Asari Radix.A retrospective, population-based cohort study was conducted, with patients randomly selected and divided into three cohorts: a non-hepatitis B virus (HBV)/hepatitis C virus (HCV) cohort, a HBV cohort, and a HCV cohort. Data were retrieved from the National Health Insurance Research Database of Taiwan from January 1, 1997 to December 31, 2013. The study period covered the initial 10 years of exposure to persistent HBV or HCV, followed by exposure to Asari Radix for an additional 8 years.After propensity score matching, 106,942, 3818, and 928 patients were included in the non-HBV/HCV, HBV, and HCV cohorts, respectively. These cohorts included 75, 50, and 42 HCCs and 1,564,943, 30,956, and 6938 person-years, respectively. All hazard ratios of exposure to 1-30 g, 31-60 g, 61-100 g, and 101-200 g of Asari Radix in these three cohorts showed negative associations between Asari Radix exposure and HCC development. Furthermore, the three cohorts demonstrated that exposure to under 200 g of Asari Radix was safe.Post-marketing surveillance showed that Asari Radix has no relationship with HCC development at an intake of under 200 g. The study is persuasive in furthering our knowledge of the maximum allowable amount of Asari Radix.