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

Abstract

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.

The genomic landscape of Mongolian hepatocellular carcinoma

“…Tobacco smoking and HBV infection were found to positively interact in liver carcinogenesis; 45,46 synergistic effects were also reported between tobacco smoking and chronic HCV leading to increased liver fibrosis 46,47 and increased risk of cirrhosis and HCC 46 . Exposure to aristolochic acids, widely used in traditional Chinese medicine throughout Asia, has been linked to liver cancer 48 , and a prospective study of HCV-infected patients in Taiwan has very recently reported an association between the intake of herbal medicines containing aristolochic acid and the risk of primary liver cancer 49 . Therefore, although the etiology of this disease and the role of HDV remain poorly understood, our findings suggest links between exposure to certain carcinogenic agents and HDV status in Mongolian HCC that deserve further investigation.…”

Dissection of cellular and molecular mechanisms of aristolochic acid-induced hepatotoxicity via single-cell transcriptomics

“…Apart from well-established kidney toxicity, it has recently been reported that AAs could also be closely related to the occurrence and pathogenesis of liver cancer due to their genotoxicities. 13 , 14 , 16 In this present study, for the first time, we used scRNA-seq technology to establish a high-resolution single-cell mouse liver atlas in response to AAI. As shown in the summary graphic, the molecular and cellular mechanisms of AAI-induced hepatotoxicity were reprogramed at the single-cell level (Fig.…”

“… 13 Herbal remedies containing AAs contribute to the risk of HCC in patients with hepatitis B or C virus infection. 14 , 15 Notably, in 2017, Ng et al . showed that AAs and their derivatives are widely implicated in liver cancers, especially in Asia, 16 where AAs quickly became the focus of public opinion, again causing widespread concern and discussion.…”

Design of Hepatic Targeted Drug Delivery Systems for Natural Products: Insights into Nomenclature Revision of Nonalcoholic Fatty Liver Disease

“…f., saikosaponin from Bupleurum chinense, geniposide from Gardenia jasminoides, and so on. The second class is those that might cause hepatocarcinoma in the presence of hepatitis B viruses, such as aristolochic acid from Aristolochia debilis and aflatoxin B1 from Aspergillus flavus (fungi) . Although the detailed modes of action responsible for biological damage in the liver by natural chemicals remain to be illustrated, a stringent liver safety evaluation of the drug candidates is essential.…”