PMID- 26484420
OWN - NLM
STAT- MEDLINE
DCOM- 20161024
LR  - 20181113
IS  - 1478-3231 (Electronic)
IS  - 1478-3223 (Print)
IS  - 1478-3223 (Linking)
VI  - 36
IP  - 2
DP  - 2016 Feb
TI  - Mechanisms of adaptation and progression in idiosyncratic drug induced liver 
      injury, clinical implications.
PG  - 158-65
LID - 10.1111/liv.12988 [doi]
AB  - In the past decade our understanding of idiosyncratic drug induced liver injury 
      (IDILI) and the contribution of genetic susceptibility and the adaptive immune 
      system to the pathogenesis of this disease process has grown tremendously. One of 
      the characteristics of IDILI is that it occurs rarely and only in a subset of 
      individuals with a presumed susceptibility to the drug. Despite a clear 
      association between single nucleotide polymorphisms in human leukocyte antigen 
      (HLA) genes and certain drugs that cause IDILI, not all individuals with 
      susceptible HLA genotypes develop clinically significant liver injury when 
      exposed to drugs. The adaptation hypothesis has been put forth as an explanation 
      for why only a small percentage of susceptible individuals develop overt IDILI 
      and severe injury, while the majority with susceptible genotypes develop only 
      mild abnormalities that resolve spontaneously upon continuation of the drug. This 
      spontaneous resolution is referred to as clinical adaptation. Failure to adapt or 
      defective adaptation leads to clinically significant liver injury. In this review 
      we explore the immuno-tolerant microenvironment of the liver and the mechanisms 
      of clinical adaptation in IDILI with a focus on the role of immune-tolerance and 
      cellular adaptive responses.
CI  - (c) 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Dara, Lily
AU  - Dara L
AD  - Research Center for Liver Disease, Keck School of Medicine, University of 
      Southern California, Los Angeles, CA, USA.
FAU - Liu, Zhang-Xu
AU  - Liu ZX
AD  - Research Center for Liver Disease, Keck School of Medicine, University of 
      Southern California, Los Angeles, CA, USA.
FAU - Kaplowitz, Neil
AU  - Kaplowitz N
AD  - Research Center for Liver Disease, Keck School of Medicine, University of 
      Southern California, Los Angeles, CA, USA.
LA  - eng
GR  - U01 AA021857/AA/NIAAA NIH HHS/United States
GR  - R01 DK067215/DK/NIDDK NIH HHS/United States
GR  - R01DK067215/DK/NIDDK NIH HHS/United States
GR  - P30DK48522/DK/NIDDK NIH HHS/United States
GR  - P30 DK048522/DK/NIDDK NIH HHS/United States
GR  - 5U01AA021857-03/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20151111
PL  - United States
TA  - Liver Int
JT  - Liver international : official journal of the International Association for the 
      Study of the Liver
JID - 101160857
RN  - 0 (HLA Antigens)
SB  - IM
MH  - *Adaptation, Physiological/genetics/immunology
MH  - *Chemical and Drug Induced Liver Injury/etiology/immunology/physiopathology
MH  - Genetic Predisposition to Disease
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - *Immune Tolerance
MH  - Severity of Illness Index
PMC - PMC4718752
MID - NIHMS731894
OTO - NOTNLM
OT  - T cells
OT  - drug induced liver injury
OT  - hepatotoxicity
OT  - human leukocyte antigen
OT  - immune-tolerance
COIS- Conflict of Interest: No direct conflicts with this review. However, NK consults 
      for the following pharmaceutical companies: Takeda, GSK, Pfizer, Daiichi-Sankyo, 
      Johnson& Johnson, Geron and Ono.
EDAT- 2015/10/21 06:00
MHDA- 2016/10/25 06:00
PMCR- 2017/02/01
CRDT- 2015/10/21 06:00
PHST- 2015/08/20 00:00 [received]
PHST- 2015/10/13 00:00 [accepted]
PHST- 2015/10/21 06:00 [entrez]
PHST- 2015/10/21 06:00 [pubmed]
PHST- 2016/10/25 06:00 [medline]
PHST- 2017/02/01 00:00 [pmc-release]
AID - 10.1111/liv.12988 [doi]
PST - ppublish
SO  - Liver Int. 2016 Feb;36(2):158-65. doi: 10.1111/liv.12988. Epub 2015 Nov 11.