Fine characterization of intrahepatic NK cells expressing natural killer receptors in chronic hepatitis B and C

J Hepatol. 2009 Sep;51(3):458-67. doi: 10.1016/j.jhep.2009.05.030. Epub 2009 Jun 25.


Background/aims: The fate of intrahepatic NK cell subsets in the course of HCV and HBV infections is not clearly understood.

Methods: Blood and intrahepatic CD56(+) NK cell subsets (expressing NKG2A, CD158a,h or CD158b,j receptors) from HCV or HBV patients were quantified by flow cytometry and localized by immunohistochemistry in liver biopsies.

Results: A significant reduction in NK cell frequency and a quantitative imbalance between CD56(bright) and CD56(dim) subsets were observed in chronic HCV patients as compared to HBV patients, underlining that the inflammatory environment is not the only cause of these phenomena. The proportions of intrahepatic NK cells expressing either NKG2A, and/or CD158a,h, CD158b,j differed significantly between HCV and HBV patients. A higher frequency of perforin among intrahepatic CD56(+)CD3(-) cells was observed in HCV compared to HBV patients. Double immunohistochemical staining showed that CD56(+)CD3(-) cells were localized within necrotic areas. Immune monitoring of circulating CD56 subsets revealed that CD3(-)CD56(bright)NKG2A(+) and CD3(-)CD56(dim)NKG2A(+) cells were positively correlated with the necroinflammatory score and inversely correlated with viral load, respectively, in HCV patients.

Conclusions: HCV and HBV affect NK cell subsets according to the status of the diseases, especially CD3(-)CD56(dim)NKG2A(+) and CD3(-)CD56(bright)NKG2A(+) cells, may be of interest for disease monitoring.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / metabolism
  • CD3 Complex / metabolism
  • CD56 Antigen / metabolism
  • Cell Count
  • Female
  • Hepatitis B, Chronic / metabolism*
  • Hepatitis B, Chronic / pathology
  • Hepatitis C, Chronic / metabolism*
  • Hepatitis C, Chronic / pathology
  • Humans
  • Killer Cells, Natural / metabolism*
  • Killer Cells, Natural / pathology
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Middle Aged
  • NK Cell Lectin-Like Receptor Subfamily C / metabolism
  • Perforin / metabolism
  • Receptors, Natural Killer Cell / metabolism*
  • Young Adult


  • Biomarkers
  • CD3 Complex
  • CD56 Antigen
  • NK Cell Lectin-Like Receptor Subfamily C
  • Receptors, Natural Killer Cell
  • Perforin