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

Grove, Jane; Aithal, Guruprasad

Authors



Abstract

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 system in 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.

Citation

Grove, J., & Aithal, G. (2014). Human leukocyte antigen genetic risk factors of drug-induced liver toxicology. Expert Opinion on Drug Metabolism and Toxicology, 11(3), 395-409. https://doi.org/10.1517/17425255.2015.992414

Journal Article Type Article
Acceptance Date Nov 7, 2014
Publication Date Dec 10, 2014
Deposit Date Aug 29, 2018
Print ISSN 1742-5255
Electronic ISSN 1744-7607
Publisher Taylor & Francis
Peer Reviewed Peer Reviewed
Volume 11
Issue 3
Pages 395-409
DOI https://doi.org/10.1517/17425255.2015.992414
Keywords adverse drug reaction, antigen presentation, drug-induced liver injury
Public URL https://nottingham-repository.worktribe.com/output/1100918
Publisher URL https://www.tandfonline.com/doi/full/10.1517/17425255.2015.992414
PMID 25491399
Additional Information This is an Accepted Manuscript of an article published by Taylor & Francis in Expert Opinion on Drug Metabolism and Toxicology on 10/12/2014, available online: http://www.tandfonline.com/10.1517/17425255.2015.992414