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HLA associations with infliximab-induced liver injury

The Pharmacogenomics Journal volume 20, pages 681–686 (2020)Cite this article

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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.

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Authors and Affiliations

  1. Emerald Lake Safety, Newport Beach, CA, USA

    Christopher D. Bruno, Brandon Fremd & Christina R. Chow

  2. Eshelman School of Pharmacy, University of North Carolina Institute for Drug Safety Sciences, Chapel Hill, NC, USA

    Rachel J. Church & Paul B. Watkins

  3. Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK

    Ann K. Daly

  4. National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK

    Guruprasad P. Aithal

  5. Department of Internal Medicine, Landspitali University Hospital, Reykjavik, Iceland

    Einar S. Björnsson

  6. Faculty of Medicine, University of Iceland, Reykjavik, Iceland

    Einar S. Björnsson

  7. Liver Unit, CHU St Eloi Hospital, Montpellier, France

    Dominique Larrey

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  1. Christopher D. Bruno
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Correspondence to Christina R. Chow.

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Conflict of interest

CDB, BF, and CRC are employees of Emerald Lake Safety. GPA is supported by the NIHR Nottingham Biomedical Research Centre. AKD has received funding from the International Serious Adverse Events Consortium for iDILIC recruitment. RJC, ESB, DL, and PBW have no conflicts to declare.

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Bruno, C.D., Fremd, B., Church, R.J. et al. HLA associations with infliximab-induced liver injury. Pharmacogenomics J 20, 681–686 (2020). https://doi.org/10.1038/s41397-020-0159-0

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