关键词: 药物性肝损伤, 人类白细胞抗原, 免疫遗传, 药物基因组学

Abstract: Drug-induced liver injury is one of the major challenges in drug development and clinical practice, and there is currently a lack of effective prevention and control measures. A growing number of studies have shown that drug-induced liver injury is mainly mediated by immune responses. Human leukocyte antigen (HLA) alleles are the strongest genetic factor reported to be associated with drug-related liver injury. Due to the low positive predictive value of HLA alleles, pre-emptive HLA gene screening has limited clinical translational value for the prevention of drug-induced liver injury; however, its high negative predictive value is valuable in the diagnosis of drug-induced liver injury and causality assessment. In recent years, polymorphisms in immune-related genes, such as antigen processing and presentation pathways, T-cell receptors, immunostimulatory molecules, and cytokines, have been found to be associated with drug-induced liver injury. In the future, analysis of these genes in conjunction with HLA may deepen the understanding of the mechanism of drug-induced liver injury, and promote their translational application in the clinic to improve drug safety in human.

Key words: drug-induced liver injury, human leukocyte antigen, immunogenetics, pharmacogenomics