Human leukocyte antigen genetic risk factors of drug-induced liver toxicology

Introduction: Drug-induced liver injury (DILI) is a rare adverse drug reaction, which impacts significantly on patients. Human leukocyte antigen (HLA) risk alleles have been found to be associated with DILI supporting an immunological basis to DILI pathogenesis. Areas covered: HLA alleles associated with risk of liver injury induced by specific therapeutic drugs are described. The evidence for a role of the adaptive immune systemin DILI is presented; case-control studies showing an association between DILI and HLA alleles are reviewed. Clinical applications of pharmacogenomics are considered. Expert opinion: Increasing evidence points to a crucial role for the adaptive immune system in the pathogenesis of DILI. Identification of specific HLA alleles as risk factors through large genome-wide association studies has been instrumental in this and in vitro analyses have facilitated improved understanding of the molecular mechanisms. This provides the basis for developing clinical pharmacogenomic applications. Already, genotyping for hypersensitivity HLA risk alleles has been implemented and opportunities for pre-prescription testing in DILI identified. However, although associations are strong, the rarity of DILI means routine testing has not been formally evaluated. Nevertheless, enhanced understanding of how HLA alleles contribute to injury risk is valuable for drug development. Translation of this research into effective pre-emption and primary prevention remains the goal.