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

OBJECTIVE: Although hepatitis B virus (HBV) DNA has been detected in the se ra of patients with chronic liver disease with neither hepatitis B surface antigen nor antihepatitis C virus antibody (non-B, non-C [NBNC] CLD), wheth er 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 perform ed 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 reac tion. Interferon-gamma (IFN-gamma) production and proliferation of PBMCs of HBV DNA-positive patients showed a significant increase in response to HBc Ag. The histological activity of hepatitis was also found to be significant ly associated with the magnitude of IFN-gamma production and proliferation of PBMCs in response to HBcAg. Although five (38%) of the 13 HBV DNA-positi ve 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 gr oups. 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. (Am J Gastroenterol 2000;95:239-247. (C) 2000 by Am. Cell. of Gastroenterology)