"Breakthrough" during interferon therapy for chronic hepatitis C. Overview on the diagnosis, possible aetiology and recommendations for management

Abstract

A relapse of serum aminotransferase levels after complete normalisation during alpha interferon therapy for chronic hepatitis C is diagnosed as Breakthrough. Its prevalence ranges between 14% and 21% of the responders, with no significant differences between the alpha interferons. Hepatitis C virus genotype and interferon dose do not seem to represent predisposing factors. The development of neutralising antibodies to interferon is associated with Breakthrough in about half of the patients; other aetiologic factors such as down-regulation of interferon receptors or development of virus resistance to interferon may be implicated in the remaining cases. The therapeutic switch from recombinant to lymphoblastoid alpha interferon has been demonstrated to be a successful strategy to overcome Breakthrough and to restore a complete response.