PMID- 32024945
OWN - NLM
STAT- MEDLINE
DCOM- 20210707
LR  - 20210707
IS  - 1473-1150 (Electronic)
IS  - 1470-269X (Linking)
VI  - 20
IP  - 5
DP  - 2020 Oct
TI  - HLA associations with infliximab-induced liver injury.
PG  - 681-686
LID - 10.1038/s41397-020-0159-0 [doi]
AB  - 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.
FAU - Bruno, Christopher D
AU  - Bruno CD
AD  - Emerald Lake Safety, Newport Beach, CA, USA.
FAU - Fremd, Brandon
AU  - Fremd B
AD  - Emerald Lake Safety, Newport Beach, CA, USA.
FAU - Church, Rachel J
AU  - Church RJ
AD  - Eshelman School of Pharmacy, University of North Carolina Institute for Drug 
      Safety Sciences, Chapel Hill, NC, USA.
FAU - Daly, Ann K
AU  - Daly AK
AD  - Translational and Clinical Research Institute, Newcastle University, Newcastle 
      upon Tyne, UK.
FAU - Aithal, Guruprasad P
AU  - Aithal GP
AD  - National Institute for Health Research (NIHR) Nottingham Biomedical Research 
      Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, 
      Nottingham, UK.
FAU - Bjornsson, Einar S
AU  - Bjornsson ES
AD  - Department of Internal Medicine, Landspitali University Hospital, Reykjavik, 
      Iceland.
AD  - Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
FAU - Larrey, Dominique
AU  - Larrey D
AD  - Liver Unit, CHU St Eloi Hospital, Montpellier, France.
FAU - Watkins, Paul B
AU  - Watkins PB
AD  - Eshelman School of Pharmacy, University of North Carolina Institute for Drug 
      Safety Sciences, Chapel Hill, NC, USA.
FAU - Chow, Christina R
AU  - Chow CR
AUID- ORCID: 0000-0003-3944-4234
AD  - Emerald Lake Safety, Newport Beach, CA, USA. christina@elsafety.com.
LA  - eng
PT  - Journal Article
DEP - 20200206
PL  - United States
TA  - Pharmacogenomics J
JT  - The pharmacogenomics journal
JID - 101083949
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-B*08:01 antigen)
RN  - 0 (HLA-B39 Antigen)
RN  - 0 (HLA-B8 Antigen)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*03:01 antigen)
RN  - B72HH48FLU (Infliximab)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anti-Inflammatory Agents/*adverse effects
MH  - Chemical and Drug Induced Liver Injury/diagnosis/*genetics/immunology
MH  - Child
MH  - Female
MH  - Genome-Wide Association Study
MH  - HLA Antigens/*genetics
MH  - HLA-B39 Antigen/genetics
MH  - HLA-B8 Antigen/genetics
MH  - HLA-DQ beta-Chains/genetics
MH  - HLA-DRB1 Chains/genetics
MH  - Humans
MH  - Infliximab/*adverse effects
MH  - Male
MH  - Middle Aged
MH  - Pharmacogenetics
MH  - *Pharmacogenomic Variants
MH  - Phenotype
MH  - *Polymorphism, Single Nucleotide
MH  - Retrospective Studies
MH  - Risk Assessment
MH  - Risk Factors
MH  - Young Adult
EDAT- 2020/02/07 06:00
MHDA- 2021/07/08 06:00
CRDT- 2020/02/07 06:00
PHST- 2019/11/13 00:00 [received]
PHST- 2020/01/27 00:00 [accepted]
PHST- 2020/01/22 00:00 [revised]
PHST- 2020/02/07 06:00 [pubmed]
PHST- 2021/07/08 06:00 [medline]
PHST- 2020/02/07 06:00 [entrez]
AID - 10.1038/s41397-020-0159-0 [pii]
AID - 10.1038/s41397-020-0159-0 [doi]
PST - ppublish
SO  - Pharmacogenomics J. 2020 Oct;20(5):681-686. doi: 10.1038/s41397-020-0159-0. Epub 
      2020 Feb 6.