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.

Abstract

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. 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. 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. 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.