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Authors
Bruno, Christopher DFremd, Brandon
Church, Rachel J
Daly, Ann K
Aithal, Guruprasad P
Björnsson, Einar S
Larrey, Dominique
Watkins, Paul B
Chow, Christina R
Issue Date
2020-02-06
Metadata
Show full item recordCitation
Bruno CD, Fremd B, Church RJ, et al. HLA associations with infliximab-induced liver injury [published online ahead of print, 2020 Feb 6]. Pharmacogenomics J. 2020;10.1038/s41397-020-0159-0. doi:10.1038/s41397-020-0159-0Abstract
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.Description
To access publisher's full text version of this article click on the hyperlink belowAdditional Links
https://www.nature.com/articles/s41397-020-0159-0ae974a485f413a2113503eed53cd6c53
10.1038/s41397-020-0159-0
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