基于转化毒理学的中药肝损害客观辨识与早期诊断

Identification and early diagnosis for traditional Chinese medicine-induced liver injury based on translational toxicology

近年来来源于中药的药源性肝损害已成为严重影响中药临床用药安全、迫切需要解决的现实性命题。早期、客观辨识药源性肝损害的致病源头,及时调整药物方案和针对性干预治疗,是减少或避免药害发生的重要前提和关键步骤。然而,目前临床判断肝损害药源主要是通过排除法,依赖患者提供的用药史和医生经验判断,缺少客观可靠的指标。由于中药多为复方用药以及临床上广泛存在中西药联合用药的情况,中药肝损害的诊断确认尤其困难,加之普遍存在"非西即中"的诊断思想,影响中药肝损害客观辩识。该文从转化毒理学的理念切入,提出构建基于转化毒理学的中药肝损害客观辨识与早期诊断研究模式和方法,以临床标本为主要研究对象,通过"临床-实验室-临床"的研究路径,采用代谢组学等组学方法筛选发现中药肝损害的相关生物标志物和特征入血成分,结合临床生化、肝穿病理指标和临床验证试验确定诊断标志物,在此基础上整合建立以诊断标志物库为核心,包含文献数据库、病历数据库、临床标本库的中药肝损害综合数据库,使临床中药肝损害药源诊断从排除法的主观模式向指标支撑的客观模式转变,以期提高中药临床合理用药能力和水平,促进中药产业健康可持续发展。

Recently traditional Chinese medicine （TCM）-induced liver injury has been an unresolved critical issue which impacts TCM clinical safety. The premise and key step to reduce or avoid drug-induced liver injury （DILI） is to identify the drug source of liver injury in early stage. Then the timely withdrawal of drug and treatment can be done. However, the current diagnosis of DILI is primarily governed by exclusive method relying on administering history supplied by patients and experience judgment from doctors, which lacks objective and reliable diagnostic indices. It is obvious that diagnosis of TCM-induced liver injury is especially difficult due to the complicated composition of TCM medication, as well the frequent combination of Chinese and Western drugs in clinic. In this paper, we proposed construction of research pattern and method for objective identification of TCM-related DILI based on translational toxicology, which utilizes clinical specimen to find specific biomarkers and characteristic blood-entering constituents, as well the clinical biochemistry and liver biopsy. With integration of diagnosis marker database, bibliographic database, medical record database and clinical specimen database, an integrative diagnosis database for TCM-related DILI can be established, which would make a transformation of clinical identification pattern for TCM-induced liver injury from subjective and exclusive to objective and index-supporting mode. This would be helpful to improve rational uses of TCM and promote sustainable development of TCM industry.