HLA associations with infliximab-induced liver injury.

Abstract

Biomarkers that are able to identify patients at risk of drug-induced liver injury (DILI) after treatment with infliximab could be important in increasing the safety of infliximab use. We performed a genetic analysis to identify possible human leukocyte antigen (HLA) associations with DILI in European Caucasian users of infliximab in a retrospective study of 16 infliximab-DILI patients and 60 matched controls. In infliximab-associated liver injury, multiple potentially causal individual HLA associations were observed, as well as possible haplotypes. The strongest associated HLA allele was HLA-B*39:01 (P = 0.001; odds ratio [OR] 43.6; 95% confidence interval [CI] 2.8-infinity), which always appeared with another associated allele C*12:03 (P = 0.032; OR 6.1; 95% CI 0.9-47.4). Other associations were observed with HLAs DQB1*02:01 (P = 0.007; OR 5.7; 95% CI 1.4-24.8), DRB1*03:01 (P = 0.012; OR 4.9; 95% CI 1.2-20.5), and B*08:01 (P = 0.048; OR 3.4; 95% CI 0.9-13.2), which also appeared together whenever present in cases. Additional associations were found with HLA-DPB1*10:01 (P = 0.042; OR 20.9; 95% CI 0.7-infinity) and HLA-DRB1*04:04 (P = 0.042; OR 20.9; 95% CI 0.7-infinity). A strong association with HLA-B*39:01 was identified as a potentially causal risk factor for infliximab-induced DILI. Future work should aim to validate this finding and explore possible mechanisms through which the biologic interacts with this particular allele.

• Authors: Christopher D Bruno, Brandon Fremd, Rachel J Church, Ann K Daly, Guruprasad P Aithal, Einar S Björnsson, Dominique Larrey, Paul B Watkins, Christina R Chow
• Journal: The pharmacogenomics journal (Pharmacogenomics J) Vol. 20 Issue 5 Pg. 681-686 (10 2020) ISSN: 1473-1150 [Electronic] United States
• PMID: 32024945 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• HLA Antigens
• HLA-B*08:01 antigen
• HLA-B39 Antigen
• HLA-B8 Antigen
• HLA-DQ beta-Chains
• HLA-DQB1 antigen
• HLA-DRB1 Chains
• HLA-DRB1*03:01 antigen
• Infliximab

Topics

• Adolescent
• Adult
• Anti-Inflammatory Agents (adverse effects)
• Chemical and Drug Induced Liver Injury (diagnosis, genetics, immunology)
• Child
• Female
• Genome-Wide Association Study
• HLA Antigens (genetics)
• HLA-B39 Antigen (genetics)
• HLA-B8 Antigen (genetics)
• HLA-DQ beta-Chains (genetics)
• HLA-DRB1 Chains (genetics)
• Humans
• Infliximab (adverse effects)
• Male
• Middle Aged
• Pharmacogenetics
• Pharmacogenomic Variants
• Phenotype
• Polymorphism, Single Nucleotide
• Retrospective Studies
• Risk Assessment
• Risk Factors
• Young Adult