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Lookup NU author(s): Professor Ann DalyORCiD
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© 2020, The Author(s), under exclusive licence to Springer Nature Limited. 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.
Author(s): Bruno CD, Fremd B, Church RJ, Daly AK, Aithal GP, Bjornsson ES, Larrey D, Watkins PB, Chow CR
Publication type: Article
Publication status: Published
Journal: Pharmacogenomics Journal
Year: 2020
Volume: 20
Pages: 681-686
Print publication date: 01/10/2020
Online publication date: 06/02/2020
Acceptance date: 27/01/2020
ISSN (print): 1470-269X
ISSN (electronic): 1473-1150
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41397-020-0159-0
DOI: 10.1038/s41397-020-0159-0
PubMed id: 32024945
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