A significant effect of the killer cell immunoglobulin-like receptor ligand human leucocyte antigen-C on fibrosis progression in chronic C hepatitis with or without liver transplantation

Liver Int. 2016 Sep;36(9):1331-9. doi: 10.1111/liv.13057. Epub 2016 Jan 24.


Background & aims: The interaction of killer cell immunoglobulin-like receptors with their human leucocyte antigen ligands drives the activation and inhibition of natural killer cells. Natural killer cells could be implicated in the development of liver fibrosis in chronic hepatitis C.

Methods: We analysed 206 non-transplanted and 53 liver transplanted patients, selected according to their Metavir fibrosis stage. Several variables such as the number of activator killer cell immunoglobulin-like receptors or the human leucocyte antigen ligands were considered in multinomial and logistic regression models. Possible confounding variables were also investigated.

Results: The killer cell immunoglobulin-like receptors were not significant predictors of the fibrosis stage. Conversely, a significant reduction of the human leucocyte antigen-C1C2 genotype was observed in the most advanced fibrosis stage group (F4) in both cohorts. Furthermore, the progression rate of fibrosis was almost 10 times faster in the subgroup of patients after liver transplantation, and human leucocyte antigen-C1C2 was significantly reduced in this cohort compared with non-transplanted patients.

Conclusion: This study suggests a possible role of killer cell immunoglobulin-like receptors and their ligands in the development of liver damage. The absence of C1 and C2 ligands heterozygosity could lead to less inhibition of natural killer cells and a quicker progression to a high level of fibrosis in patients infected with hepatitis C virus, especially following liver transplantation.

Keywords: HLA; KIR; chronic C hepatitis; fibrosis; liver transplantation.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Disease Progression
  • Female
  • Gene Frequency
  • Genotype
  • HLA-C Antigens / genetics*
  • Hepacivirus
  • Hepatitis C, Chronic / complications*
  • Humans
  • Killer Cells, Natural / immunology
  • Liver / pathology
  • Liver Cirrhosis / genetics*
  • Liver Transplantation*
  • Logistic Models
  • Male
  • Middle Aged
  • Receptors, KIR / genetics*
  • Switzerland


  • HLA-C Antigens
  • Receptors, KIR