马兜铃酸与肝癌相关性的研究及思考

2017年国际期刊Science Translational Medicine 杂志发表了马兜铃酸（aristolochic acids, AAs）及其衍生物与肝癌发生相关的研究，文章发表后引起了广泛关注和巨大争议。尽管AAs可致肾毒性和泌尿系肿瘤早已获得广泛共识，国际癌症研究中心（IARC）也将AAs列为第一类致癌物，但是该研究仍然冲击了人们对肝癌发生的普遍认知。之后，2018年International Journal of Cancer 杂志发表的一项基于我国台湾地区全民医疗数据库的流行病学研究进一步提出含有AAs的中草药可能是乙肝相关肝癌发生的另一重要风险因素；而最新发表在Hepatology杂志的文章结果表明单独给予AAs即可诱导幼龄小鼠肝癌发生，这似乎又为AAs诱导肝癌增添了新的证据。然而，在多项采用成年小鼠和大鼠的研究中均未观察到AAs可诱发肝癌，因此AAs致肝癌的客观性还有待验证。为科学客观地看待AAs与肝癌的关系，避免误导我国肝癌防控策略出现大的偏差，同时促进AAs相关制剂安全性的科学监管，笔者梳理了AAs与肝癌相关性的研究，并探讨了目前研究中存在的问题，并对今后工作重点和应对措施提出了建议。

Research and Thinking on the Relationship between Aristolochic Acids and Liver Cancer

In 2017, the international journal Science Translational Medicine reported that aristolochic acids (AAs) and their derivatives are widely implicated in liver cancers. The study caused widespread concern and great controversy once it was published. Although the toxic effects of AAs on kidneys and their effects on urinary tumors have long been widely recognized, and the International Agency for Research on Cancer (IARC) has classified AAs as the first class of carcinogens, the studies still impacted people??s general perception of liver cancer. Then, in 2018, an epidemiological study published in the International Journal of Cancer based on the National Medical Database in Taiwan further suggested that the Chinese herbal medicines containing AAs may be another important risk factor for hepatitis B-related liver cancer. The results of a recent study published in Hepatology showed that AAs alone can induce liver cancer in young mice, which seems to add new evidence for the view that AAs can induce liver cancer. It should be noted that AAs can induce liver cancer has never been observed in previous studies using adult mice or adult rats. Therefore, its objectivity remains to be verified. In order to scientifically and objectively treat the relationship between AAs and liver cancer, avoid misleading the prevention and control strategies of liver cancer in China and promote the scientific supervision of the safety of AAs- related preparations, this paper comprehensively analyzed and discussed research progress of the correlation between AAs and liver cancer, and made recommendations for future work priorities and response measures.