State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
J Clin Transl Hepatol. 2014 Sep;2(3):162-9. doi: 10.14218/JCTH.2014.00015. Epub 2014 Sep 15.
Drug-induced liver injury (DILI) is a leading cause of acute liver failure, and a major reason for the recall of marketed drugs. Detection of potential liver injury is a challenge for clinical management and preclinical drug safety studies, as well as a great obstacle to the development of new, effective and safe drugs. Currently, serum levels of alanine and aspartate aminotransferases are the gold standard for evaluating liver injury. However, these levels are assessed by nonspecific, insensitive, and non-predictive tests, and often result in false-positive results. Therefore, there is an urgent need for better DILI biomarkers to guide risk assessment and patient management. The discovery of microRNAs (miRNAs) as a new class of gene expression regulators has triggered an explosion of research, particularly on the measurement of miRNAs in various body fluids as biomarkers for many human diseases. The properties of miRNA-based biomarkers, such as tissue specificity and high stability and sensitivity, suggest they could be used as novel, minimally invasive and stable DILI biomarkers. In the current review, we summarize recent progress concerning the role of miRNAs in diagnosing and monitoring both clinical and preclinical DILI, and discuss the main advantages and challenges of miRNAs as novel DILI biomarkers.
药物性肝损伤(DILI)是急性肝衰竭的主要原因,也是导致已上市药物召回的主要原因之一。检测潜在的肝损伤对临床管理和临床前药物安全性研究都是一个挑战,也是开发新的有效和安全药物的巨大障碍。目前,血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平是评估肝损伤的金标准。然而,这些水平是通过非特异性、不敏感和非预测性的检测来评估的,并且常常导致假阳性结果。因此,迫切需要更好的 DILI 生物标志物来指导风险评估和患者管理。microRNAs(miRNAs)作为一类新的基因表达调控因子的发现引发了研究的爆炸式增长,特别是在各种体液中测量 miRNA 作为许多人类疾病的生物标志物方面。miRNA 生物标志物的特性,如组织特异性和高稳定性和敏感性,表明它们可作为新型微创和稳定的 DILI 生物标志物。在当前的综述中,我们总结了 miRNA 在诊断和监测临床和临床前 DILI 方面的最新进展,并讨论了 miRNA 作为新型 DILI 生物标志物的主要优势和挑战。