Lower number and decreased function of natural killer cells in hepatitis B virus related acute-on-chronic liver failure

Clin Res Hepatol Gastroenterol. 2016 Nov;40(5):605-613. doi: 10.1016/j.clinre.2016.01.004. Epub 2016 Apr 1.

Abstract

Background: Hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) refers to acute deterioration occurring in patients with chronic hepatitis B infected liver diseases. An abnormality in NK cells mediated cellular immunity is believed to be a contributing factor. We aimed to evaluate the characteristic of NK cells in the peripheral blood of HBV related ACLF.

Methods: Flow cytometric method was used to detect the absolute numbers and subgroups of NK cells, and analyze the cytotoxicity and killing ability of NK cells in patients with HBV-ACLF.

Results: The results showed that peripheral numbers of NK cells were decreased in patients with HBV-ACLF, but not statistically significant. The cytotoxic CD56dimCD16bright NK cells were significantly decreased in HBV infected patients, especially ACLF patients. The CD56brightCD16- subgroup was expanded in patients with CHB and the CD56dimCD16- subgroup was expanded in patients with ACLF. The activating receptors of NKG2D, NKp30, NKp44, and NKp46 were increased in patients with ACLF. The inhibitory receptors of CD158a were increased, though the CD158b was decreased in patients of ACLF. The function of NK cells including cytotoxicity and killing activity were both downregulated in patients with ACLF and CHB. Even if after IL-12/15 stimulation, INF-γ and TNF-α produced by patients with ACLF were still less than those produced by healthy controls.

Conclusions: Patients with HBV-ACLF had lower numbers and decreased functions of cytotoxic NK cells.

MeSH terms

  • Acute-On-Chronic Liver Failure / metabolism*
  • Acute-On-Chronic Liver Failure / virology*
  • Adult
  • Aged
  • CD56 Antigen / metabolism
  • Down-Regulation
  • Female
  • Flow Cytometry
  • Hepatitis B virus
  • Hepatitis B, Chronic / complications*
  • Humans
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / metabolism*
  • Male
  • Middle Aged
  • Receptors, IgG / metabolism
  • Receptors, Natural Cytotoxicity Triggering / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult

Substances

  • CD56 Antigen
  • Receptors, IgG
  • Receptors, Natural Cytotoxicity Triggering
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma