Allison Rebecca, Guraka Asha, Shawa Isaac Thom, Tripathi Gyan, Moritz Wolfgang, Kermanizadeh Ali
College of Science and Technology, University of Derby, Derby, UK.
School of Science and Technology, Nottingham Trent University, Nottingham, UK.
J Toxicol Environ Health B Crit Rev. 2023 Nov 17;26(8):442-467. doi: 10.1080/10937404.2023.2261848. Epub 2023 Oct 19.
Drug-Induced Liver Injury (DILI) constitutes hepatic damage attributed to drug exposure. DILI may be categorized as hepatocellular, cholestatic or mixed and might also involve immune responses. When DILI occurs in dose-dependent manner, it is referred to as intrinsic, while if the injury occurs spontaneously, it is termed as idiosyncratic. This review predominately focused on idiosyncratic liver injury. The established molecular mechanisms for DILI include (1) mitochondria dysfunction, (2) increased reactive oxygen species levels, (3) presence of elevated apoptosis and necrosis, (4) and bile duct injuries associated with immune mediated pathways. However, it should be emphasized that the underlying mechanisms responsible for DILI are still unknown. Prevention strategies are critical as incidences occur frequently, and treatment options are limited once the injury has developed. The aim of this review was to utilize retrospective cohort studies from across the globe to gain insight into epidemiological patterns. This review considers (1) what is currently known regarding the mechanisms underlying DILI, (2) discusses potential risk factors and (3) implications of the coronavirus pandemic on DILI presentation and research. Future perspectives are also considered and discussed and include potential new biomarkers, causality assessment and reporting methods.
药物性肝损伤（DILI）是指由药物暴露引起的肝损伤。DILI可分为肝细胞型、胆汁淤积型或混合型，也可能涉及免疫反应。当DILI以剂量依赖方式发生时，称为固有型，而如果损伤自发发生，则称为特异质性。本综述主要关注特异质性肝损伤。已确定的DILI分子机制包括：（1）线粒体功能障碍；（2）活性氧水平升高；（3）细胞凋亡和坏死增加；（4）与免疫介导途径相关的胆管损伤。然而，应该强调的是，DILI的潜在机制仍然未知。预防策略至关重要，因为其发病率频繁发生，而且一旦损伤发生，治疗选择有限。本综述的目的是利用来自全球的回顾性队列研究，深入了解流行病学模式。本综述考虑了：（1）目前已知的DILI潜在机制；（2）讨论潜在风险因素；（3）冠状病毒大流行对DILI表现和研究的影响。还考虑并讨论了未来展望，包括潜在的新生物标志物、因果关系评估和报告方法。
