ANTIBODIES TO INTERFERON (IFN) IN HEPATITIS-C PATIENTS RELAPSING WHILE CONTINUING RECOMBINANT IFN-ALPHA-2 THERAPY

A number of trials have demonstrated that IFN-alpha is effective in ch ronic hepatitis C virus infection. It is known, however, that a number of chronic hepatitis C patients experience, after an initial response to IFN, disease reactivation or relapse (also called 'breakthrough') while IFN therapy is still ongoing. Since in a number of clinical cond itions a significant correlation between development of antibodies to IFN and failure of therapy has been established, we addressed the poss ibility that the development of antibodies to IFN may take part in the relapse occurring in hepatitis C patients during recombinant IFN-alph a (rIFN-alpha) therapy. The prevalence of neutralizing (NA) and bindin g antibodies (BA) to rIFN-alpha 2 has been evaluated in 45 patients wi th chronic hepatitis C treated with rIFN-alpha 2a who first normalized aminotransferase (ALT) levels, and subsequently showed disease reacti vation while on treatment. The presence of NA and BA was tested before therapy, during the response to IFN treatment, and at the time when A LT started to rise again to abnormal levels. The results showed that n o patients had detectable antibodies to IFN before therapy and during the period of response to the therapy, while most of them (88.9%) deve loped NA and/or BA to IFN alpha 2 concomitantly with disease reactivat ion. In particular, in 29 of the 45 patients (64.4%) ALT normalized on treatment and rose to abnormal levels when NA appeared in their serum , while in 11 of the 16 (68.8%) remaining patients the relapse was ass ociated with BA development. The frequency of seroconversion in these patients is significantly higher than that observed in the control gro up. These data indicate that antibodies to IFN may be responsible for breakthrough in the majority of patients showing disease reactivation while rIFN-alpha therapy is still ongoing.