Absence of activating killer immunoglobulin-like receptor genes combined with hepatitis C viral genotype is predictive of hepatocellular carcinoma

Hum Immunol. 2013 Oct;74(10):1288-94. doi: 10.1016/j.humimm.2013.05.007. Epub 2013 Jun 10.

Abstract

Killer immunoglobulin-like receptors and their human leukocyte antigen class I ligands have a critical role in natural killer cell response to viral pathogens and tumors. To investigate whether killer immunoglobulin-like receptor genes could influence the chronic course of hepatitis C virus infection and/or progression to hepatocellular carcinoma we retrospectively analyzed a cohort of 228 patients transplanted for hepatitis C virus-induced cirrhotic end stage liver disease, combined or not with hepatocellular carcinoma. We found that patients completely lacking activating killer immunoglobulin-like receptor genes had a high risk of developing hepatocellular carcinoma. Hepatitis C viral genotype and viral load are other risk factors that can influence the course of chronic hepatitis C virus infection. In our study, the risk conferred by hepatitis C viral genotypes was enhanced in patients lacking activating killer immunoglobulin-like receptors. These results point to an important role for activating killer immunoglobulin-like receptors in the control of hepatitis C virus infection and progression to hepatocellular carcinoma. In clinical practice, assessment of killer immunoglobulin-like receptor and hepatitis C viral genotype combinations should allow for more accurate monitoring of patients with chronic hepatitis C virus infection.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / virology*
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genotype*
  • Haplotypes
  • Hepatitis C / genetics*
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / virology
  • Histocompatibility Antigens / genetics
  • Histocompatibility Antigens / immunology
  • Humans
  • Ligands
  • Liver Cirrhosis / etiology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / immunology
  • Liver Neoplasms / virology*
  • Male
  • Middle Aged
  • Receptors, KIR / genetics*
  • Receptors, KIR / immunology
  • Retrospective Studies
  • Viral Load

Substances

  • Histocompatibility Antigens
  • Ligands
  • Receptors, KIR