Moreno-Torres Marta, Quintás Guillermo, Castell José V
Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria Hospital La Fe, 46026 Valencia, Spain.
CIBEREHD, Instituto de Salud Carlos III, 28029 Madrid, Spain.
Metabolites. 2022 Jun 19;12(6):564. doi: 10.3390/metabo12060564.
Drug-induced liver injury (DILI) is one of the most frequent adverse clinical reactions and a relevant cause of morbidity and mortality. Hepatotoxicity is among the major reasons for drug withdrawal during post-market and late development stages, representing a major concern to the pharmaceutical industry. The current biochemical parameters for the detection of DILI are based on enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP)) and bilirubin serum levels that are not specific of DILI and therefore there is an increasing interest on novel, specific, DILI biomarkers discovery. Metabolomics has emerged as a tool with a great potential for biomarker discovery, especially in disease diagnosis, and assessment of drug toxicity or efficacy. This review summarizes the multistep approaches in DILI biomarker research and discovery based on metabolomics and the principal outcomes from the research performed in this field. For that purpose, we have reviewed the recent scientific literature from PubMed, Web of Science, EMBASE, and PubTator using the terms "metabolomics", "DILI", and "humans". Despite the undoubted contribution of metabolomics to our understanding of the underlying mechanisms of DILI and the identification of promising novel metabolite biomarkers, there are still some inconsistencies and limitations that hinder the translation of these research findings into general clinical practice, probably due to the variability of the methods used as well to the different mechanisms elicited by the DILI causing agent.
药物性肝损伤（DILI）是最常见的临床不良反应之一，也是发病和死亡的一个相关原因。肝毒性是药物在上市后和后期研发阶段撤市的主要原因之一，是制药行业主要关注的问题。目前用于检测DILI的生化参数基于酶（丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、γ-谷氨酰转肽酶（GGT）、碱性磷酸酶（ALP））和胆红素血清水平，这些并非DILI所特有的，因此对新型、特异性DILI生物标志物的发现越来越受到关注。代谢组学已成为一种在生物标志物发现方面具有巨大潜力的工具，尤其是在疾病诊断以及药物毒性或疗效评估方面。本综述总结了基于代谢组学的DILI生物标志物研究与发现的多步骤方法以及该领域研究的主要成果。为此，我们使用“代谢组学”“DILI”和“人类”等术语，检索了来自PubMed、科学网、EMBASE和PubTator的近期科学文献。尽管代谢组学对我们理解DILI的潜在机制以及识别有前景的新型代谢物生物标志物做出了毋庸置疑的贡献，但仍存在一些不一致和局限性，阻碍了这些研究结果转化为一般临床实践，这可能是由于所用方法的变异性以及DILI致病剂引发的不同机制所致。
