Association analysis of KIR/HLA genotype with liver cirrhosis, hepatocellular carcinoma, and NUC freedom in chronic hepatitis B patients

Sci Rep. 2021 Nov 2;11(1):21424. doi: 10.1038/s41598-021-01014-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / virology
  • Female
  • Follow-Up Studies
  • Genotype
  • HLA-B Antigens / genetics*
  • Hepatitis B virus / isolation & purification
  • Hepatitis B, Chronic / complications*
  • Hepatitis B, Chronic / virology
  • Humans
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / pathology*
  • Liver Cirrhosis / virology
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Nucleosides / therapeutic use*
  • Prognosis
  • Receptors, KIR / genetics*
  • Receptors, KIR3DL1 / genetics*
  • Retrospective Studies

Substances

  • HLA-B Antigens
  • HLA-Bw4 antigen
  • KIR2DS3 protein, human
  • KIR3DL1 protein, human
  • Nucleosides
  • Receptors, KIR
  • Receptors, KIR3DL1