Intrahepatic natural killer cell activation, but not function, is associated with HBsAg levels in patients with HBeAg-negative chronic hepatitis B
Article first published online: 25 JUL 2013
© 2013 John Wiley & Sons A/S. Publishing by John Wiley & Sons Ltd.
Volume 34, Issue 3, pages 396–404, March 2014
How to Cite
Liver Int. 2014: 34: 396–404
- Issue published online: 7 FEB 2014
- Article first published online: 25 JUL 2013
- Accepted manuscript online: 3 JUL 2013 04:45AM EST
- Manuscript Accepted: 25 JUN 2013
- Manuscript Received: 2 JAN 2013
- Dutch government. Grant Number: FES0908
- Netherlands Genomics Initiative (NGI). Grant Number: 050–060–452
- HBV ;
- innate immunity;
- NK cells;
- viral hepatitis
Background & Aims
Natural killer (NK) cells play an important role in the immune response to viruses. As the hepatitis B virus (HBV) replicates in hepatocytes, examination of the liver of chronic hepatitis B (CHB) patients is crucial to better understand the role of NK cells in HBV. HBeAg-negative CHB differs in many aspects from HBeAg-positive CHB, and until now little is known about the intrahepatic NK cell response in HBeAg-negative patients. Intrahepatic immune control might be different in HBeAg-negative as compared with HBeAg-positive patients.
Liver NK cells were investigated in 21 HBeAg-positive and 35 HBeAg-negative CHB patients. Biopsy specimens were processed for routine histopathology and staging according to Ishak scores. Intrahepatic and blood NK cell frequencies, activation status and function of NK cells were analysed by flow cytometry.
In HBeAg-negative CHB patients, compared to blood, liver NK cells displayed a more activated phenotype and stimulation further increased the activation status, but production of IFN-γ was markedly less. There was no difference with HBeAg-positive CHB. Only in HBeAg-negative CHB, but not in HBeAg-positive CHB, NK cell activation was inversely correlated with HBsAg levels.
The present study indicates that liver NK cells of CHB have a higher activation status compared to blood. However, they are not capable to increase cytokine production above levels reached by activated blood NK cells. In HBeAg-negative CHB, the levels of HBsAg may contribute to the incapacity of activated liver NK cells to increase cytokine production.