Although Recombinant interferon alpha (r-IFN alpha 2) has initially been shown to normalize the aminotransferase levels in approximately 50% of patients with chronic hepatitis C virus (HCV), a few patients experience a relapse during the treatment, in spite of a complete initial response (breakthrough). Continued treatment with r-IFN alpha 2, even at higher doses, did not restore the previous response in any patient. All of them were then switched to natural lymphoblastoid IFN, and this rapidly restored a complete response in all of the patients. - “Breakthrough during recombinant interferon alpha therapy in patients with chronic hepatitis C virus infection: prevalence, etiology, and management.” (Hepatology Vol. 21 no. 3 pp. 645-9, 1995 Mar.)
A report in the Archive of Virology 1997;142(3):535-544 suggests that an unapparent coinfection (also known as an occult infection) of the hepatitis B virus (HBV) along with the hepatitis C virus may be implicated in cases of resistance to interferon treatment. In addition, HBV replication may persist in patients in whom HCV replication was inhibited by interferon treatment.
“The development of neutralizing 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.” Genotype does not seem to make a difference (Ital J Gastroenterol Hepatol. 1998 Jun;30[3]:333-7. Unique Identifier: AIDSLINE MED/98431771).
