Drug-Induced Liver Injury due to Flucloxacillin: Relevance of Multiple Human Leukocyte Antigen Alleles.
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Aithal, Guruprasad P
Chamberlain, Thomas C
Grove, Jane I
Andrade, Raul J
Dillon, John F
Lucena, M Isabel
Maitland-van der Zee, Anke H
Martin, Jennifer H
Nelson, Matthew R
Daly, Ann K
MetadataShow full item record
CitationDrug-Induced Liver Injury due to Flucloxacillin: Relevance of Multiple Human Leukocyte Antigen Alleles. 2019, 106(1):245-253 Clin Pharmacol Ther
AbstractSome 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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- HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin.
- Authors: Daly AK, Donaldson PT, Bhatnagar P, Shen Y, Pe'er I, Floratos A, Daly MJ, Goldstein DB, John S, Nelson MR, Graham J, Park BK, Dillon JF, Bernal W, Cordell HJ, Pirmohamed M, Aithal GP, Day CP, DILIGEN Study., International SAE Consortium.
- Issue date: 2009 Jul
- The safety of flucloxacillin in HIV-infected patients with positive HLA-B*5701 genotype.
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- Issue date: 2013 Jan 28
- Genetic association studies in drug-induced liver injury.
- Authors: Daly AK, Day CP
- Issue date: 2009 Nov
- Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-Wide Association Study.
- Authors: Nicoletti P, Aithal GP, Bjornsson ES, Andrade RJ, Sawle A, Arrese M, Barnhart HX, Bondon-Guitton E, Hayashi PH, Bessone F, Carvajal A, Cascorbi I, Cirulli ET, Chalasani N, Conforti A, Coulthard SA, Daly MJ, Day CP, Dillon JF, Fontana RJ, Grove JI, Hallberg P, Hernández N, Ibáñez L, Kullak-Ublick GA, Laitinen T, Larrey D, Lucena MI, Maitland-van der Zee AH, Martin JH, Molokhia M, Pirmohamed M, Powell EE, Qin S, Serrano J, Stephens C, Stolz A, Wadelius M, Watkins PB, Floratos A, Shen Y, Nelson MR, Urban TJ, Daly AK, International Drug-Induced Liver Injury Consortium, Drug-Induced Liver Injury Network Investigators, and International Serious Adverse Events Consortium.
- Issue date: 2017 Apr
- Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles.
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- Issue date: 2011 Jul