PMID- 34209910
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210711
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 13
IP  - 13
DP  - 2021 Jun 29
TI  - Investigation of the Effect of KIR-HLA Pairs on Hepatocellular Carcinoma in 
      Hepatitis C Virus Cirrhotic Patients.
LID - 10.3390/cancers13133267 [doi]
LID - 3267
AB  - Natural killer cells are partially mediated through the binding of killer cell 
      immunoglobulin-like receptors (KIR) with human leukocyte antigen (HLA) class I 
      ligands. This investigation examined the risk of hepatocellular carcinoma (HCC) 
      in relation to KIR-HLA pairs in patients with compensated hepatitis C virus 
      (HCV)-associated cirrhosis. A total of 211 Japanese compensated HCV cirrhotic 
      cases were retrospectively enrolled. After KIR, HLA-A, HLA-Bw, and HLA-C typing, 
      associations between HLA, KIR, and KIR-HLA combinations and HCC development were 
      evaluated using the Cox proportional hazards model with the stepwise method. 
      During a median follow-up period of 6.6 years, 69.7% of patients exhibited HCC. 
      The proportions of HLA-Bw4 and the KIR3DL1 + HLA-Bw4 pair were significantly 
      higher in patients with HCC than in those without (78.9% vs. 64.1%; odds ratio 
      (OR)-2.10, 95% confidence interval (CI)-1.10-4.01; p = 0.023 and 76.2% vs. 60.9%, 
      odds ratio-2.05, p = 0.024, respectively). Multivariate analysis revealed the 
      factors of male gender (hazard ratio (HR)-1.56, 95% CI-1.12-2.17; p = 0.009), 
      alpha-fetoprotein > 5.6 ng/mL (HR-1.56, 95% CI-1.10-2.10; p = 0.011), and KIR3DL1 + 
      HLA-Bw4 (HR-1.69, 95% CI-1.15-2.48; p = 0.007) as independent risk factors for 
      developing HCC. Furthermore, the cumulative incidence of HCC was significantly 
      higher in patients with KIR3DL1 + HLA-Bw4 than in those without (log-rank test; p 
      = 0.013). The above findings suggest KIR3DL1 + HLA-Bw4, in addition to HLA-Bw4, 
      as a novel KIR-HLA pair possibly associated with HCC development in HCV 
      cirrhosis. HCV-associated cirrhotic patients with the risk factors of male 
      gender, alpha-fetoprotein > 5.6 ng/mL, and KIR3DL1 + HLA-Bw4 may require careful 
      surveillance for HCC onset.
FAU - Umemura, Takeji
AU  - Umemura T
AUID- ORCID: 0000-0001-7985-919X
AD  - Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu 
      University School of Medicine, Matsumoto 390-8621, Nagano, Japan.
AD  - Consultation Center for Liver Diseases, Shinshu University Hospital, Matsumoto 
      390-8621, Nagano, Japan.
AD  - Department of Life Innovation, Shinshu University, Matsumoto 390-8621, Nagano, 
      Japan.
FAU - Joshita, Satoru
AU  - Joshita S
AUID- ORCID: 0000-0002-6364-9654
AD  - Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu 
      University School of Medicine, Matsumoto 390-8621, Nagano, Japan.
FAU - Saito, Hiromi
AU  - Saito H
AD  - Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu 
      University School of Medicine, Matsumoto 390-8621, Nagano, Japan.
FAU - Wakabayashi, Shun-Ichi
AU  - Wakabayashi SI
AD  - Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu 
      University School of Medicine, Matsumoto 390-8621, Nagano, Japan.
FAU - Kobayashi, Hiroyuki
AU  - Kobayashi H
AD  - Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu 
      University School of Medicine, Matsumoto 390-8621, Nagano, Japan.
FAU - Yamashita, Yuki
AU  - Yamashita Y
AUID- ORCID: 0000-0002-0162-4208
AD  - Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu 
      University School of Medicine, Matsumoto 390-8621, Nagano, Japan.
FAU - Sugiura, Ayumi
AU  - Sugiura A
AUID- ORCID: 0000-0001-5427-7628
AD  - Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu 
      University School of Medicine, Matsumoto 390-8621, Nagano, Japan.
FAU - Yamazaki, Tomoo
AU  - Yamazaki T
AD  - Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu 
      University School of Medicine, Matsumoto 390-8621, Nagano, Japan.
FAU - Ota, Masao
AU  - Ota M
AUID- ORCID: 0000-0002-6400-5658
AD  - Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu 
      University School of Medicine, Matsumoto 390-8621, Nagano, Japan.
LA  - eng
GR  - 20K08282/Japan Society for the Promotion of Science/
PT  - Journal Article
DEP - 20210629
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8267716
OTO - NOTNLM
OT  - cirrhosis
OT  - hepatitis C virus
OT  - hepatocellular carcinoma
OT  - human leukocyte antigen
OT  - killer cell immunoglobulin-like receptors
OT  - natural killer cells
COIS- The authors declare no conflict of interest.
EDAT- 2021/07/03 06:00
MHDA- 2021/07/03 06:01
PMCR- 2021/06/29
CRDT- 2021/07/02 01:40
PHST- 2021/04/20 00:00 [received]
PHST- 2021/06/21 00:00 [revised]
PHST- 2021/06/25 00:00 [accepted]
PHST- 2021/07/02 01:40 [entrez]
PHST- 2021/07/03 06:00 [pubmed]
PHST- 2021/07/03 06:01 [medline]
PHST- 2021/06/29 00:00 [pmc-release]
AID - cancers13133267 [pii]
AID - cancers-13-03267 [pii]
AID - 10.3390/cancers13133267 [doi]
PST - epublish
SO  - Cancers (Basel). 2021 Jun 29;13(13):3267. doi: 10.3390/cancers13133267.