中药特异质肝损伤评价及风险防控对策研究

Evaluation and Risk Control of Idiosyncratic Liver Injury Caused by Traditional Chinese Medicine

近年来,传统"无毒"中药致肝损伤问题屡见报道,引起人们对中药安全性的广泛关注并在业内引起争议。长期以来,中药肝损伤主要集中于直接肝毒性研究,尚未从机体易感性角度开展特异质肝损伤研究。笔者课题组在国内外开辟了中药特异质肝损伤研究新领域,采用首创的药源性肝损伤客观辨识方法和诊断标准等技术手段,研究证实了何首乌等传统"无毒"中药肝损伤的客观性和特异质属性,并结合其致肝损伤临床特点,提出并建立了关联临床病证的中药安全性评价模式和方法——病证毒理学,系统揭示了何首乌、淫羊藿等中药致特异质肝损伤的病证基础及易感机制,并据此建立了中药安全性风险"人-药-用"三维警戒技术体系,应用于系列中药的安全性风险防控对策制定,实现了中药安全性评价与防控从单纯"以药找毒"向结合"因人避毒"方向转变,有效指导临床安全合理用药。综述近年来中药特异质肝损伤评价及风险防控对策研究进展,以期为临床安全合理用药和后续研究提供指导和支持。

In recent years,the report of adverse reactions of traditional Chinese medicines(TCMs),especially the traditional non-toxic TCM-induced liver injuries have been arising,causing serious concerns about the safety of TCM from the public with heated controversy.Previous studies have focused on the direct toxic components of TCM,with little attention and research on idiosyncratic drug-induced liver injury(IDILI).Our team has established the new field of research on the TCM-related IDILI,and confirmed the objectivity and immune-specific properties of liver injury caused by a series of traditional non-toxic TCMs such as Polygonum multiflorum using the integrated evidence chain-based identification strategy for IDILI.Especially,we presented a novel and clinic-associated safety assessment strategy,namely"disease-syndrome-based toxicology",for TCMs,which can systematically access the susceptibility mechanism of IDILI casued by Polygonum multiflorum and Epimedium.On this basis,we first proposed and established a three-dimensional pharmacovigilance system of TCM based on the identification of susceptible population,quality control of susceptible substances and clinical precise drug use as a comprehensive prevention and control method,which could be applied for the TCM safety risk prevention and control countermeasures against a series of IDILI.The safety evaluation and control of TCM was transformed from simply"finding toxicity with medicine"to combining it with"avoiding toxicity for patients",which could effectively guide clinical safe and rational use of drugs.This paper reviews the research progress of IDILI in recent years in order to provide guidance and support for clinical safe and rational use of drugs and follow-up research.