PMID- 25491399
OWN - NLM
STAT- MEDLINE
DCOM- 20150914
LR  - 20161125
IS  - 1744-7607 (Electronic)
IS  - 1742-5255 (Linking)
VI  - 11
IP  - 3
DP  - 2015 Mar
TI  - Human leukocyte antigen genetic risk factors of drug-induced liver toxicology.
PG  - 395-409
LID - 10.1517/17425255.2015.992414 [doi]
AB  - INTRODUCTION: Drug-induced liver injury (DILI) is a rare adverse drug reaction, 
      which impacts significantly on patients. Human leukocyte antigen (HLA) risk 
      alleles have been found to be associated with DILI supporting an immunological 
      basis to DILI pathogenesis. AREAS COVERED: HLA alleles associated with risk of 
      liver injury induced by specific therapeutic drugs are described. The evidence 
      for a role of the adaptive immune system in DILI is presented; case-control 
      studies showing an association between DILI and HLA alleles are reviewed. 
      Clinical applications of pharmacogenomics are considered. EXPERT OPINION: 
      Increasing evidence points to a crucial role for the adaptive immune system in 
      the pathogenesis of DILI. Identification of specific HLA alleles as risk factors 
      through large genome-wide association studies has been instrumental in this and 
      in vitro analyses have facilitated improved understanding of the molecular 
      mechanisms. This provides the basis for developing clinical pharmacogenomic 
      applications. Already, genotyping for hypersensitivity HLA risk alleles has been 
      implemented and opportunities for pre-prescription testing in DILI identified. 
      However, although associations are strong, the rarity of DILI means routine 
      testing has not been formally evaluated. Nevertheless, enhanced understanding of 
      how HLA alleles contribute to injury risk is valuable for drug development. 
      Translation of this research into effective pre-emption and primary prevention 
      remains the goal.
FAU - Grove, Jane I
AU  - Grove JI
AD  - Nottingham University Hospitals NHS Trust and University of Nottingham, NIHR 
      Nottingham Digestive Diseases Biomedical Research Unit , Nottingham, NG7 2UH , UK 
      +01159249924 Ext: 63822 ; +01159709012 ; Guru.Aithal@nottingham.ac.uk.
FAU - Aithal, Guruprasad P
AU  - Aithal GP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20141210
PL  - England
TA  - Expert Opin Drug Metab Toxicol
JT  - Expert opinion on drug metabolism & toxicology
JID - 101228422
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - Chemical and Drug Induced Liver Injury/etiology/*genetics
MH  - *Genetic Predisposition to Disease
MH  - Genetic Testing/methods
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - Pharmacogenetics
MH  - Risk Factors
OTO - NOTNLM
OT  - MHC
OT  - adverse drug reaction
OT  - antigen presentation
OT  - drug-induced liver injury
EDAT- 2014/12/11 06:00
MHDA- 2015/09/15 06:00
CRDT- 2014/12/11 06:00
PHST- 2014/12/11 06:00 [entrez]
PHST- 2014/12/11 06:00 [pubmed]
PHST- 2015/09/15 06:00 [medline]
AID - 10.1517/17425255.2015.992414 [doi]
PST - ppublish
SO  - Expert Opin Drug Metab Toxicol. 2015 Mar;11(3):395-409. doi: 
      10.1517/17425255.2015.992414. Epub 2014 Dec 10.