HLA associations with infliximab-induced liver injury

Pharmacogenomics J. 2020 Oct;20(5):681-686. doi: 10.1038/s41397-020-0159-0. Epub 2020 Feb 6.

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.

MeSH terms

  • Adolescent
  • Adult
  • Anti-Inflammatory Agents / adverse effects*
  • Chemical and Drug Induced Liver Injury / diagnosis
  • Chemical and Drug Induced Liver Injury / genetics*
  • Chemical and Drug Induced Liver Injury / 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

Substances

  • 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