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Drug-Induced Liver Injury due to Flucloxacillin: Relevance of Multiple Human Leukocyte Antigen Alleles.

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Authors
Nicoletti, Paola
Aithal, Guruprasad P
Chamberlain, Thomas C
Coulthard, Sally
Alshabeeb, Mohammad
Grove, Jane I
Andrade, Raul J
Bjornsson, Einar
Dillon, John F
Hallberg, Par
Lucena, M Isabel
Maitland-van der Zee, Anke H
Martin, Jennifer H
Molokhia, Mariam
Pirmohamed, Munir
Wadelius, Mia
Shen, Yufeng
Nelson, Matthew R
Daly, Ann K
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Issue Date
2019-07

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Citation
Drug-Induced Liver Injury due to Flucloxacillin: Relevance of Multiple Human Leukocyte Antigen Alleles. 2019, 106(1):245-253 Clin Pharmacol Ther
Abstract
Some patients prescribed flucloxacillin (~ 0.01%) develop drug-induced liver injury (DILI). HLA-B*57:01 is an established genetic risk factor for flucloxacillin DILI. To consolidate this finding, identify additional genetic factors, and assess relevance of risk factors for flucloxacillin DILI in relation to DILI due to other penicillins, we performed a genomewide association study involving 197 flucloxacillin DILI cases and 6,835 controls. We imputed single-nucleotide polymorphism and human leukocyte antigen (HLA) genotypes. HLA-B*57:01 was the major risk factor (allelic odds ratio (OR) = 36.62; P = 2.67 × 10-97 ). HLA-B*57:03 also showed an association (OR = 79.21; P = 1.2 × 10-6 ). Within the HLA-B protein sequence, imputation showed valine97 , common to HLA-B*57:01 and HLA-B*57:03, had the largest effect (OR = 38.1; P = 9.7 × 10-97 ). We found no HLA-B*57 association with DILI due to other isoxazolyl penicillins (n = 6) or amoxicillin (n = 15) and no significant non-HLA signals for any penicillin-related DILI.
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https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1002/cpt.1375
ae974a485f413a2113503eed53cd6c53
10.1002/cpt.1375
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English Journal Articles (Peer Reviewed)

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