中药药源性肝损伤因果关系的评价策略和方法

Causality assessment strategies and methods for Chinese medicines-induced liver injury

中药药源性肝损伤是中药临床应用中常见的严重不良反应之一,一直困扰着中药新药研发、临床安全用药及产业化发展。阐明肝损伤与中药之间的因果关系是极具挑战的国际性难题,也是正确认识中药安全性问题的前提和关键。然而,由于中药自身的复杂性以及临床上影响中药药源性肝损伤的因素众多,患者肝损伤与中药之间的因果关系更是难以评价;同时现有的评价方法主要是针对临床诊疗设计的,不适用于中药新药的研发以及上市后再评价。为此,本文综述分析了国内外主要因果关系评价方法的类型和优缺点,进一步以新药研发中的药源性肝损伤因果关系评价为目标,结合中药复杂性特点,提出基于整合证据链的中药药源性肝损伤因果关系评价新策略和新方法,以期科学厘定患者肝损伤与中药之间的因果关系,提高中药新药研发成功率,更好地发现、规避和防范中药药源性肝损伤风险,为公众健康服务。

Chinese medicines （CM）-induced liver injury is one of the severe adverse drug reactions （ADRs） in clinical application, which restricts new drug research and development （R＆D）, clinical safe usage and industry development of CM. The issue, to elucidate the causality between liver injury and CM, is either a globally challenging problem or the precondition of CM safety evaluation. However, owing to the complexicity of CM and various influencing factors to CM-induced liver injury, the causality assessment for CM is much difficult, compared to synthetic drugs. Besides, the current assessment methods, primarily designed for clinical diagnosis, are difficult to be used in new drug R＆D of CM. Hereinto, we reviewed the current ADR causality methods and proposed a new strategy called integrated evidence chain-based causality assessment method for CM-induced liver injury. The new causality method is designed for new drug R＆D based on the complexicity of CM, to provide methodology in scientific assessment of causality of CM-induced liver injury and to promote success rate of new drug R＆D. The new method could also raise our ability to find, avoid and prevent the risk of CM-induced liver injury.