Role of hepatitis B virus in non-B, non-C chronic liver disease: in vitro proliferation and interferon-gamma production of peripheral blood mononuclear cells in response to hepatitis B core antigen and its relation to hepatitis activity

Am J Gastroenterol. 2000 Jan;95(1):239-47. doi: 10.1111/j.1572-0241.2000.01650.x.

Abstract

Objective: Although hepatitis B virus (HBV) DNA has been detected in the sera of patients with chronic liver disease with neither hepatitis B surface antigen nor antihepatitis C virus antibody (non-B, non-C [NBNC] CLD), whether HBV has some pathogenic role in NBNC CLD has not been made clear.

Methods: To investigate the significance of HBV DNA in NBNC CLD, we performed in vitro stimulation assays of peripheral blood mononuclear cells (PBMCs) in response to hepatitis B core antigen (HBcAg) in 17 NBNC CLD patients.

Results: HBV DNA with an 8-nucleotide deletion in the core promoter region was detected in 13 (76%) of the 17 patients by nested polymerase chain reaction. Interferon-gamma (IFN-gamma) production and proliferation of PBMCs of HBV DNA-positive patients showed a significant increase in response to HBcAg. The histological activity of hepatitis was also found to be significantly associated with the magnitude of IFN-gamma production and proliferation of PBMCs in response to HBcAg. Although five (38%) of the 13 HBV DNA-positive NBNC CLD patients had anti-HBs and/or anti-HBc, there was no difference in response of PBMCs to HBcAg between the HBV DNA-positive and -negative groups.

Conclusion: Our observation suggests that HBV may have a pathogenic role in HBV DNA-positive NBNC CLD, even in those patients without any serological markers of HBV.

MeSH terms

  • Adult
  • Aged
  • DNA, Viral / analysis
  • Female
  • Hepatitis B Core Antigens / analysis
  • Hepatitis B Core Antigens / immunology*
  • Hepatitis B Surface Antigens / analysis
  • Hepatitis B virus / isolation & purification*
  • Hepatitis, Chronic / immunology
  • Hepatitis, Chronic / pathology
  • Hepatitis, Chronic / virology*
  • Hepatitis, Viral, Human / immunology
  • Hepatitis, Viral, Human / pathology
  • Hepatitis, Viral, Human / virology*
  • Humans
  • Immunohistochemistry
  • Interferon-gamma / biosynthesis*
  • Leukocytes, Mononuclear / immunology*
  • Liver / immunology
  • Liver / pathology
  • Lymphocyte Activation*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction

Substances

  • DNA, Viral
  • Hepatitis B Core Antigens
  • Hepatitis B Surface Antigens
  • Interferon-gamma