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  • Title: Role of anti-interferon antibodies in breakthrough occurrence during alpha 2a and 2b therapy in patients with chronic hepatitis C.
    Author: Leroy V, Baud M, de Traversay C, Maynard-Muet M, Lebon P, Zarski JP.
    Journal: J Hepatol; 1998 Mar; 28(3):375-81. PubMed ID: 9551673.
    Abstract:
    BACKGROUND/AIMS: Alpha interferon induces aminotransferase normalization in about 50% of patients with chronic viral hepatitis C. However, some patients who initially respond experience a relapse during the treatment period (breakthrough phenomenon). The aim of this study was to evaluate the prevalence of breakthrough and its relationship with the emergence of neutralizing anti-interferon antibodies. METHODS: We studied 172 patients with histologically proven chronic hepatitis C, treated with interferon alpha 2a or 2b 3 mega units three times a week for 6 months. For each patient, HCV RNA level (polymerase chain reaction and bDNA) and anti-interferon antibodies dosage were determined during therapy. RESULTS: Among 84 patients with initial response, 13 (15.5%) experienced breakthrough. The kinetics of alanine aminotransferase and HCV RNA levels were strongly correlated, suggesting that breakthrough is not due to a random alanine aminotransferase fluctuation during treatment, but to the reappearance of viral replication. Neutralizing anti-interferon antibodies emergence was observed in 38.5% in patients with breakthrough, as compared to 9.0% and 2.8% of non-responder and complete-responder patients, respectively (p<0.0005). By multivariate analysis, the only factor predictive of breakthrough was the emergence of neutralizing anti-interferon antibodies 3 months after the onset of therapy. CONCLUSION: Our results suggest that the emergence of neutralizing anti-interferon antibodies during treatment may explain breakthrough in about one third of cases. Other causes may also be responsible for this phenomenon and they remain to be determined.
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