PMID- 26540496
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20151106
LR  - 20220408
IS  - 2092-7355 (Print)
IS  - 2092-7363 (Electronic)
IS  - 2092-7355 (Linking)
VI  - 8
IP  - 1
DP  - 2016 Jan
TI  - Update on Advances in Research on Idiosyncratic Drug-Induced Liver Injury.
PG  - 3-11
LID - 10.4168/aair.2016.8.1.3 [doi]
AB  - Drug-induced liver injury (DILI) is a major concern for public health, as well as 
      for drug development in the pharmaceutical industry, since it can cause liver 
      failure and lead to drug withdrawal from the market and black box warnings. Thus, 
      it is important to identify biomarkers for early prediction to increase our 
      understanding of mechanisms underlying DILI that will ultimately aid in the 
      exploration of novel therapeutic strategies to prevent or manage DILI. DILI can 
      be subdivided into 'intrinsic' and 'idiosyncratic' categories, although the 
      validity of this classification remains controversial. Idiosyncratic DILI occurs 
      in a minority of susceptible individuals with a prolonged latency, while 
      intrinsic DILI results from drug-induced direct hepatotoxicity over the course of 
      a few days. The rare occurrence of idiosyncratic DILI requires multicenter 
      collaborative investigations and phenotype standardization. Recent progress in 
      research on idiosyncratic DILI is based on key developments in 3 areas: (1) newly 
      developed high-throughput genotyping across the whole genome allowing for the 
      identification of genetic susceptibility markers, (2) new mechanistic concepts on 
      the pathogenesis of DILI revealing a key role of drug-responsive T lymphocytes in 
      the immunological response, and (3) broad multidisciplinary approaches using 
      different platform "-omics" technologies that have identified novel biomarkers 
      for the prediction of DILI. An association of a specific human leukocyte antigen 
      (HLA) allele with DILI has been reported for several drugs. HLA-restricted T-cell 
      immune responses have also been investigated using lymphocytes and T-cell clones 
      isolated from patients. A microRNA, miR-122, has been discovered as a promising 
      biomarker for the early prediction of DILI. In this review, we summarize recent 
      advances in research on idiosyncratic DILI with an understanding of the key role 
      of adaptive immune systems.
FAU - Kim, Seung Hyun
AU  - Kim SH
AD  - Department of Allergy and Clinical Immunology, Ajou University School of 
      Medicine, Suwon, Korea.
FAU - Naisbitt, Dean J
AU  - Naisbitt DJ
AD  - MRC Centre for Drug Safety Science, Department of Clinical and Molecular 
      Pharmacology, Sherrington Building, Ashton Street, The University of Liverpool, 
      Liverpool, L69 3 GE, England. dnes@liv.ac.uk.
LA  - eng
GR  - MR/L006758/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Review
DEP - 20150703
PL  - Korea (South)
TA  - Allergy Asthma Immunol Res
JT  - Allergy, asthma & immunology research
JID - 101518382
PMC - PMC4695405
OTO - NOTNLM
OT  - Drug-induced liver injury
OT  - T-cell
OT  - biomarker
OT  - hapten
OT  - human leukocyte antigen
OT  - immune response
COIS- There are no financial or other issues that might lead to conflict of interest.
EDAT- 2015/11/06 06:00
MHDA- 2015/11/06 06:01
PMCR- 2016/01/01
CRDT- 2015/11/06 06:00
PHST- 2015/03/11 00:00 [received]
PHST- 2015/04/13 00:00 [accepted]
PHST- 2015/11/06 06:00 [entrez]
PHST- 2015/11/06 06:00 [pubmed]
PHST- 2015/11/06 06:01 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - 201601003 [pii]
AID - 10.4168/aair.2016.8.1.3 [doi]
PST - ppublish
SO  - Allergy Asthma Immunol Res. 2016 Jan;8(1):3-11. doi: 10.4168/aair.2016.8.1.3. 
      Epub 2015 Jul 3.