HCV replication in mononuclear cells stimulates anti‐HCV‐secreting B cells and reflects nonresponsiveness to interferon‐α

Recently, it was demonstrated in chronic hepatitis C that the release of IgG and IgM anti‐HCV antibodies by mononuclear cells (PBMCs) correlated with inflammatory activity, HCV persistence in serum, and negative outcome from antiviral therapy. Thus, persistent antigenic stimulation of the antibody‐secreting B cells has been suggested. In this study, PBMCs were derived from 13 patients with chronic hepatitis C. Nucleic acids were extracted by the guanidine‐thiocy‐anate‐method, and plus‐ and minus‐stranded HCV‐RNAs were determined using primers from the 5′‐untranslated region of HCV. Simultaneously, unstimulated PBMCs were cultured for 8 days and anti‐HCV antibodies were detected in the supernatants by EIA and RIBA. Seven patients (53.8%) had both plus‐ and minus‐stranded HCV‐RNA in PBMCs, while anti‐HCV antibodies were secreted in vitro. One of 2 patients with plus‐ but not minus‐stranded HCV‐ RNA in PBMCs was anti‐HCV positive in vitro, whereas 4 patients without HCV‐infected PBMCs were anti‐HCV negative in vitro. Eight patients received antiviral therapy with interferon‐α2b. Four nonresponders and 1 partial responder had plus‐ and minus‐stranded HCV‐ RNA in PBMCs and anti‐HCV secretion in vitro. On the other hand, 2 complete responders and another partial responder showed neither HCV infection of PBMCs nor anti‐HCV secretion in vitro. In conclusion, infection of PBMCs by HCV is observed frequently in patients with chronic hepatitis C, and may be related to the high rate of nonresponders to antiviral treatment. The close correlation of anti‐HCV secretion in vitro and viral replication suggests that the humoral response to HCV is triggered by viral antigens that are expressed on infected mononuclear cells.