Immunological responses in patients who have spontaneously eradicated hepatitis C virus infection

We examined the proliferative responses of peripheral blood mononuclear cells obtained from 60 untreated patients who were seropositive by enzyme immunoassay, but negative for hepatitis C virus (HCV) RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). We used second- and third-generation recombinant immunoblot assay (RIBA) for further serological characterization. In vitro HCV-specific proliferative responses of mononuclear cells were compared to those of both untreated chronic HCV patients and patients who showed sustained virological response to interferon-alpha monotherapy, in order to assess the relative contribution of the immune response to the eradication of HCV. We found that frequency of responses to nonstructural proteins showed statistically significant differences, which were attributable to vigorous, polyspecific responses by cells from the RIBA-positive patients. In this group, core-specific proliferation was significantly associated with intravenous drug use as route of acquisition. Both other patient groups and the RIBA-indeterminate patients showed indistinguishable frequencies of proliferative responses. No association was detected between residual humoral responses, as determined from the RIBA results, and elapsed time since infection. The frequency of antibodies to NS5 differs between spontaneous cure and chronically infected patients. Cell-mediated and humoral immunity appear to be maintained in this population of patients.