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Record W2908525626 · doi:10.1002/cpt.1375

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

2019· article· en· W2908525626 on OpenAlexaff
Paola Nicoletti, Guruprasad P. Aithal, Thomas C. Chamberlain, Sally A. Coulthard, Mohammad A. Alshabeeb, Jane I. Grove, Raúl J. Andrade, Einar S. Björnsson, John Dillon, Pär Hallberg, M. Isabel Lucena, Anke H. Maitland‐van der Zee, Jennifer Martin, Mariam Molokhia, Munir Pirmohamed, Mia Wadelius, Yufeng Shen, Matthew R. Nelson, Ann K. Daly

Bibliographic record

VenueClinical Pharmacology & Therapeutics · 2019
Typearticle
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicDrug-Induced Hepatotoxicity and Protection
Canadian institutionsUniversity of British Columbia
FundersNIHR Nottingham Biomedical Research CentreEuropean Regional Development FundMedical Research CouncilSvenska LäkaresällskapetUppsala UniversitetRadboud Universitair Medisch CentrumKarolinska InstitutetUniversity of NottinghamKing's College LondonDaiichi-SankyoAbbott LaboratoriesNational Institute for Health and Care ResearchBiotechnology and Biological Sciences Research CouncilWellcome TrustNottingham University Hospitals NHS TrustKing’s College LondonRocheInstituto de Salud Carlos IIIAmgenRadboud UniversiteitNewcastle UniversityNovartisAstraZenecaVetenskapsrådetUniversity of WarwickPfizerMerckDirectorate for Biological SciencesGlaxoSmithKlineSanofiWellcomeUniversiteit Utrecht
KeywordsFlucloxacillinHuman leukocyte antigenOdds ratioAlleleMedicineImmunologyPenicillinHLA-BGenotypeInternal medicineBiologyAntigenAntibioticsGeneGeneticsStaphylococcus aureus

Abstract

fetched live from OpenAlex

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 valine 97 , 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 .

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.222
GPT teacher head0.486
Teacher spread0.264 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations89
Published2019
Admission routes1
Has abstractyes

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