Role of anti-interferon antibodies in breakthrough occurrence during alpha 2a and 2b therapy in patients with chronic hepatitis C

Background/Aims: Alpha interferon induces amino-transferase 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 meek 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.