BREAKTHROUGH DURING THERAPY WITH NATURAL INTERFERONS ALPHA FOR CHRONIC HEPATITIS C

G. Bellati, L. Roffi, G.Antonelli[, G. Colloredo, M. Currentis, A. Bellobuono, F. Bissoli!, M. D'Acquino{}, M. Pozzi, A. Ricci, A. Redaelli, G.Ideo, F. Dianzani$, G. Mancia and C.H.S.G.a Internal Medicine Niguarda Hospital, Milan; Chair Internal Medicine, S.Gerardo Hospital, Monza (MI); ?Inst. of Virology, University of Pisa, Pisa; Chair Internal Medicine, Bolognini Hospital, Seriate (BG); $Institute of Virology, University of Rome, Rome; !Magenta Hospital, Magenta (MI); {}Internal Medicine Mestre Hospital (VE); a Chronic Hepatitis Study Group; Italy

Breakthrough (BREAK) in chronic hepatitis C has been defined as increasing serum ALT levels more than two times over the upper normal limit, for at least two consecutive months, during the IFN treatment after an initial normalization.

Breakthrough is not an exceedingly rare phenomenon. A recent investigation showed that it is not only confined to r-IFN\alpha. In fact, in a large series of patients, no significant differences in breakthrough prevalence between different type of either recombinant or natural IFN\alpha was found. Nevertheless, further informations were available, till now, only on r-IFN\alpha2. In this case neutralizing IFN antibodies seems to have a key role in about 50% of patients.

METHODS. The prevalence of BREAK in 39 responders to leucocyte IFN\alpha (Leuc-IFN\alpha), and 104 responders to natural lymphoblastoid IFN\alpha (l-IFN\alphaNl) was analized. All patients were enrolled and treated in open studies for chronic hepatitis C.

RESULTS. BREAK occurred in 4 patients (10.2% of responders) treated with Leuc-IFN\alpha, approximately 5 months after the start of therapy; and in 21 patients (20.2% of responders) treated with 1-IFN\alphaN1, approximately 4.5 months after the start of therapy. We had the opportunity to collect monthly the blood samples of all BREAK patients treated with Leuc-IFN\alpha and of 3 patients experiencing BREAK during l-IFN\alphaNl therapy. The samples were examined for the presence of antibodies to IFN\alpha2, which is one of the mostly represented subtype in the mixture of natural IFN\alpha. In 1 patient treated with Leuc-IFN\alpha we were able to document the presence of neutralizing antibodies. In the same group 2 patients had also binding antibodies. No patients treated with 1-IFN\alphaN1 had evidence of neutralizing or binding antibodies. Studies are in progress to evaluate whether sera from these patients contain antibodies specifically directed against each subtype present in the natural mixture of IFN\alpha.

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