PMID- 32039386
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220412
IS  - 2589-5559 (Electronic)
IS  - 2589-5559 (Linking)
VI  - 1
IP  - 5
DP  - 2019 Nov
TI  - KIR/HLA genotypes confer susceptibility and progression in patients with 
      autoimmune hepatitis.
PG  - 353-360
LID - 10.1016/j.jhepr.2019.09.003 [doi]
AB  - Natural killer (NK) cells are key participants in the innate immune response. 
      Killer cell immunoglobulin-like receptors (KIRs) are involved in the activation 
      and inhibition of NK cells through the recognition of human leukocyte antigen 
      (HLA) class I molecules. We investigated the impact of KIR/HLA combinations on 
      susceptibility and long-term clinical outcome in Japanese patients with type 1 
      autoimmune hepatitis (AIH). METHODS: A total of 154 cases of AIH were recruited 
      at Shinshu University Hospital between 1974 and 2018. KIR genes and HLA class I 
      and II alleles were genotyped in all patients along with 201 healthy individuals. 
      Associations between KIR/HLA pairs and clinical outcomes (liver decompensation 
      and liver-related death) were evaluated using the Cox proportional hazards model 
      with stepwise method. RESULTS: After a median follow-up period of 11.1 years, 12% 
      of patients experienced liver decompensation and 8% died from liver disease. 
      KIR3DL1/HLA-B Bw4-80Ile (p = 0.0062) and the HLA-DRB1*04:05-DQB1*04:01 haplotype 
      (p <<0.001) were significantly associated with AIH. Conversely, significant 
      protective associations were found for KIR3DL1/HLA-B Bw4-80Thr (p = 0.0092) and 
      KIR2DL1/HLA-C2 (p = 0.0025). The KIR3DL1/HLA-B Bw4-positive phenotype was 
      strongly associated with a favorable clinical outcome (liver decompensation: 
      hazard ratio [HR] 0.37, p = 0.037; liver-related death: HR 0.26, p = 0.038). 
      Cirrhosis was detected in 16 (10%) patients at diagnosis and was significantly 
      related to poor survival (HR 17.87, p <<0.001) and progression to liver 
      decompensation (HR 9.00, p <<0.001). CONCLUSIONS: This study revealed the impact 
      of specific KIR/HLA pairs in AIH susceptibility and progression in Japanese 
      patients. KIR3DL1/HLA-B Bw4-negative patients with AIH and cirrhosis at diagnosis 
      are at high risk of adverse outcomes and require careful surveillance. LAY 
      SUMMARY: Autoimmune hepatitis (AIH) is a disease of the liver that can present in 
      acute or chronic hepatitis. We examined whether KIR/HLA pairs were associated 
      with AIH susceptibility or disease progression. KIR3DL1/HLA-B Bw4 was a novel 
      KIR/HLA pair related to a favorable clinical outcome, while cirrhosis at the 
      initial diagnosis was a risk factor for poor prognosis. Thus, frequent and 
      careful surveillance is advised for KIR3DL1/HLA-B Bw4-negative patients with AIH 
      and cirrhosis.
CI  - (c) 2019 The Authors.
FAU - Umemura, Takeji
AU  - Umemura T
AD  - Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu 
      University School of Medicine, Matsumoto, Japan.
AD  - Department of Life Innovation, Institute for Biomedical Sciences, Shinshu 
      University, Matsumoto, Japan.
FAU - Joshita, Satoru
AU  - Joshita S
AD  - Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Saito, Hiromi
AU  - Saito H
AD  - Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Yoshizawa, Kaname
AU  - Yoshizawa K
AD  - Department of Gastroenterology, NHO Ueda Medical Center, Ueda, Japan.
FAU - Norman, Gary L
AU  - Norman GL
AD  - Inova Diagnostics, San Diego, USA.
FAU - Tanaka, Eiji
AU  - Tanaka E
AD  - Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Ota, Masao
AU  - Ota M
AD  - Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu 
      University School of Medicine, Matsumoto, Japan.
LA  - eng
PT  - Journal Article
DEP - 20191025
PL  - Netherlands
TA  - JHEP Rep
JT  - JHEP reports : innovation in hepatology
JID - 101761237
PMC - PMC7005656
OTO - NOTNLM
OT  - AIH
OT  - HLA
OT  - Killer cell immunoglobulin-like receptors
OT  - NK cell
OT  - outcome
EDAT- 2020/02/11 06:00
MHDA- 2020/02/11 06:01
PMCR- 2019/10/25
CRDT- 2020/02/11 06:00
PHST- 2019/07/09 00:00 [received]
PHST- 2019/09/12 00:00 [revised]
PHST- 2019/09/19 00:00 [accepted]
PHST- 2020/02/11 06:00 [entrez]
PHST- 2020/02/11 06:00 [pubmed]
PHST- 2020/02/11 06:01 [medline]
PHST- 2019/10/25 00:00 [pmc-release]
AID - S2589-5559(19)30108-9 [pii]
AID - 10.1016/j.jhepr.2019.09.003 [doi]
PST - epublish
SO  - JHEP Rep. 2019 Oct 25;1(5):353-360. doi: 10.1016/j.jhepr.2019.09.003. eCollection 
      2019 Nov.