INTERFERON ANTIBODIES IN PATIENTS WITH CHRONIC HEPATITIC-C VIRUS-INFECTION TREATED WITH RECOMBINANT INTERFERON ALPHA-2-ALPHA

Patients treated with alpha-2a interferon for chronic hepatitis C may produce anti-interferon antibodies whose effect, if any, on the individual response to therapy has not been fully clarified. The prevalence and kinetics of anti-interferon, including those of neutralizing type, have been studied in 60 patients with chronic hepatitis C enrolled in a randomized controlled trial of recombinant alpha-2a interferon. Thirty patients received interferon while 30 were untreated controls. Two different methods, an enzyme immunoassay and an antiviral neutralization bioassay, were used and serial serum. samples from each patient were analyzed. Enzyme immunoassay-positive anti-interferon appeared in 60.7% of treated patients within 6 months of therapy; antiviral neutralization bioassay-positive anti-interferon appeared in 52.9% of these enzyme immunoassay-positive patients, and was associated with high enzyme immunoassay reactivity and long-term persistence. Anti-interferon was detected in 75% of patients showing no response to interferon. Antibodies were also detected in three out of six patients who showed alanine aminotransferase normalization persisting up to the end of treatment and in 8 out of 14 patients who showed an initial marked reduction or even normalization of alanine aminotransferase, followed by reactivation of liver damage during treatment. Interestingly, patients who became anti-interferon positive before complete alanine aminotransferase normalization later showed reactivation of liver damage independently of interferon dose reduction, while patients who became positive for anti-interferon after complete alanine aminotransferase normalization either did not reactivate or did so only after interferon dose reduction. These results seem to indicate that anti-interferon may interfere with the biochemical response to interferon in some patients with chronic hepatitis C and that this interference is closely dependent on whether anti-interferon appears before or after a response. (C) Journal of Hepatology.