Human Leukocyte Antigen (HLA) Signatures and Idiosyncratic Drug-Induced Liver Injury

Area of Science:

• Immunogenetics
• Pharmacogenomics
• Hepatology

Background:

• Drug-induced liver injury (DILI) is a major clinical challenge, especially its unpredictable, idiosyncratic form.
• Host genetic factors, particularly human leukocyte antigen (HLA) variations, are implicated in DILI pathogenesis.
• Drug-protein adducts acting as neoantigens can trigger immune responses leading to liver injury.

Purpose of the Study:

• To review the role of HLA polymorphisms in the development of idiosyncratic DILI.
• To highlight specific HLA alleles associated with DILI risk for various drugs.
• To discuss the potential of HLA typing for personalized DILI prevention strategies.

Main Methods:

• Review of current scientific literature and genomic studies.
• Analysis of associations between specific HLA alleles and DILI cases.
• Examination of ethnic variations and allele-haplotype interactions in DILI susceptibility.

Main Results:

• Strong associations found between specific HLA alleles and DILI risk (e.g., HLA-B*57:01 with flucloxacillin, HLA-DRB1*15:01-DQB1*06:02 with amoxicillin-clavulanate, HLA-B*35:02 with minocycline).
• HLA polymorphisms contribute significantly to the immunogenetic basis of idiosyncratic DILI.
• Ethnic variability and complex genetic interactions may modulate DILI risk and presentation.

Conclusions:

• HLA signatures are crucial in understanding idiosyncratic DILI.
• Identifying at-risk individuals through HLA typing offers a path toward precision medicine.
• Targeted genetic screening can improve the prevention of severe drug-induced liver injury.