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



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
et al (show 10 more authors) (2019) Drug-Induced Liver Injury due to Flucloxacillin: Relevance of Multiple Human Leukocyte Antigen Alleles. CLINICAL PHARMACOLOGY & THERAPEUTICS, 106 (1). pp. 245-253.

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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.

Item Type: Article
Uncontrolled Keywords: International Drug-Induced Liver Injury Consortium (iDILIC), Humans, Penicillins, Floxacillin, HLA-B Antigens, Anti-Bacterial Agents, Genotype, Polymorphism, Single Nucleotide, Aged, Middle Aged, Female, Male, Genome-Wide Association Study, Chemical and Drug Induced Liver Injury
Depositing User: Symplectic Admin
Date Deposited: 31 Oct 2019 11:35
Last Modified: 19 Jan 2023 00:21
DOI: 10.1002/cpt.1375
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3060098