PMID- 34728722 OWN - NLM STAT- MEDLINE DCOM- 20220124 LR - 20220124 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 11 IP - 1 DP - 2021 Nov 2 TI - Association analysis of KIR/HLA genotype with liver cirrhosis, hepatocellular carcinoma, and NUC freedom in chronic hepatitis B patients. PG - 21424 LID - 10.1038/s41598-021-01014-x [doi] LID - 21424 AB - Natural killer cells are modulated through the binding of killer cell immunoglobulin-like receptors (KIRs) with human leukocyte antigen (HLA) class I ligands. This study investigated the association of KIR/HLA pairs with progression to liver cirrhosis, hepatocellular carcinoma (HCC) development, and nucleot(s)ide (NUC) treatment freedom in hepatitis B virus (HBV) infection. KIR, HLA-Bw, and HLA-C were genotyped in 280 Japanese HBV patients for clinical comparisons. No significant associations of KIR/HLA pairs were detected in terms of liver cirrhosis development. The KIR2DS3 positive rate was significantly higher in patients with HCC (n = 39) than in those without (n = 241) [30.8% vs. 14.9%, odds ratio (OR) 2.53, P = 0.015]. The KIR3DL1/HLA-Bw4 pair rate was significantly lower in the NUC freedom group (n = 20) than in the NUC continue group (n = 114) (25.0% vs. 52.6%, OR 0.30, P = 0.042). In conclusion, this study indicated remarkable associations of KIR/HLA with HCC development (KIR2DS3) and freedom from NUC therapy (KIR3DL1/HLA-Bw4) in HBV patients, although the number of cases was insufficient for statistical purposes. Additional multi-center analyses of larger groups are needed to clarify whether KIR/HLA pairs play a role in HBV patient status. CI - (c) 2021. The Author(s). FAU - Joshita, Satoru AU - Joshita S AD - Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. joshita@shinshu-u.ac.jp. AD - Department of Health Promotion Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. joshita@shinshu-u.ac.jp. FAU - Ota, Masao AU - Ota M AD - Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. AD - Department of Health Promotion Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. FAU - Kobayashi, Hiroyuki AU - Kobayashi H AD - Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. AD - Department of Health Promotion Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. FAU - Wakabayashi, Shun-Ichi AU - Wakabayashi SI AD - Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. FAU - Yamashita, Yuki AU - Yamashita Y AD - Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. FAU - Sugiura, Ayumi AU - Sugiura A AD - Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. FAU - Yamazaki, Tomoo AU - Yamazaki T AD - Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. FAU - Tanaka, Eiji AU - Tanaka E AD - Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. FAU - Umemura, Takeji AU - Umemura T AD - Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. AD - Department of Health Promotion Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. AD - Consultation Center for Liver Diseases, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. AD - Department of Life Innovation, Institute for Biomedical Sciences, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. LA - eng GR - 18K08000/Japan Society for the Promotion of Science/ GR - 18K08000/Japan Society for the Promotion of Science/ GR - 20K08282/Japan Society for the Promotion of Science/ GR - 18K08000/Japan Society for the Promotion of Science/ GR - JP21fk0210084/Japan Agency for Medical Research and Development/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211102 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (HLA-B Antigens) RN - 0 (HLA-Bw4 antigen) RN - 0 (KIR2DS3 protein, human) RN - 0 (KIR3DL1 protein, human) RN - 0 (Nucleosides) RN - 0 (Receptors, KIR) RN - 0 (Receptors, KIR3DL1) SB - IM MH - Aged MH - Carcinoma, Hepatocellular/drug therapy/genetics/*pathology/virology MH - Female MH - Follow-Up Studies MH - Genotype MH - HLA-B Antigens/*genetics MH - Hepatitis B virus/isolation & purification MH - Hepatitis B, Chronic/*complications/virology MH - Humans MH - Liver Cirrhosis/drug therapy/genetics/*pathology/virology MH - Liver Neoplasms/drug therapy/genetics/*pathology/virology MH - Male MH - Middle Aged MH - Nucleosides/*therapeutic use MH - Prognosis MH - Receptors, KIR/*genetics MH - Receptors, KIR3DL1/*genetics MH - Retrospective Studies PMC - PMC8563771 COIS- The authors declare no competing interests. EDAT- 2021/11/04 06:00 MHDA- 2022/01/27 06:00 PMCR- 2021/11/02 CRDT- 2021/11/03 06:33 PHST- 2021/07/22 00:00 [received] PHST- 2021/10/21 00:00 [accepted] PHST- 2021/11/03 06:33 [entrez] PHST- 2021/11/04 06:00 [pubmed] PHST- 2022/01/27 06:00 [medline] PHST- 2021/11/02 00:00 [pmc-release] AID - 10.1038/s41598-021-01014-x [pii] AID - 1014 [pii] AID - 10.1038/s41598-021-01014-x [doi] PST - epublish SO - Sci Rep. 2021 Nov 2;11(1):21424. doi: 10.1038/s41598-021-01014-x.