School of Medicine, Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK.
National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals Nhs Trust and the University of Nottingham, Nottingham, UK.
Expert Opin Drug Metab Toxicol. 2021 Nov;17(11):1327-1343. doi: 10.1080/17425255.2021.1999410. Epub 2021 Nov 15.
Idiosyncratic drug-induced liver injury (DILI) is an unpredictable event, and there are no specific biomarkers that can distinguish DILI from alternative explanations or predict its clinical outcomes.
This systematic review summarizes the available evidence for all biomarkers proposed to have a role in the diagnosis or prognosis of DILI. Following a comprehensive search, we included all types of studies in humans. We included DILI cases based on any threshold criteria but excluded intrinsic DILI, commonly caused by paracetamol overdose. We classified studies into diagnostic and prognostic categories and assessed their methodological quality. After reviewing the literature, 14 studies were eligible.
Diagnostic studies were heterogeneous with regard to the study population and outcomes measured. Prognostic models were developed by integrating novel biomarkers, risk scores, and traditional biomarkers, which increased their prognostic ability to predict death or transplantation by 6 months. This systematic review highlights the case of need for non-genetic biomarkers that distinguish DILI from acute liver injury related to alternative etiology. Biomarkers with the potential to identify serious adverse outcomes from acute DILI should be validated in independent prospective cohorts with a substantial number of cases.
药物性肝损伤（DILI）具有不可预测性，目前尚无特定的生物标志物可用于区分 DILI 与其他原因引起的肝损伤，或预测其临床结局。
本系统综述总结了所有被提出用于诊断或预测 DILI 的生物标志物的现有证据。通过全面检索，我们纳入了所有类型的人类研究。我们纳入了基于任何阈值标准的 DILI 病例，但排除了由乙酰氨基酚过量引起的固有 DILI。我们将研究分为诊断和预后两类，并评估了其方法学质量。文献回顾后，有 14 项研究符合条件。
诊断研究在研究人群和测量结果方面存在异质性。预后模型是通过整合新型生物标志物、风险评分和传统生物标志物而建立的，这提高了它们预测 6 个月内死亡或移植的预后能力。本系统综述强调了需要非遗传生物标志物来区分 DILI 与其他病因引起的急性肝损伤的情况。具有区分急性 DILI 严重不良结局潜力的生物标志物应在具有大量病例的独立前瞻性队列中进行验证。
