P. Bonetti et al., INTERFERON ANTIBODIES IN PATIENTS WITH CHRONIC HEPATITIC-C VIRUS-INFECTION TREATED WITH RECOMBINANT INTERFERON ALPHA-2-ALPHA, Journal of hepatology, 20(3), 1994, pp. 416-420
Patients treated with alpha-2a interferon for chronic hepatitis C may
produce anti-interferon antibodies whose effect, if any, on the indivi
dual 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. Thi
rty patients received interferon while 30 were untreated controls. Two
different methods, an enzyme immunoassay and an antiviral neutralizat
ion bioassay, were used and serial serum. samples from each patient we
re analyzed. Enzyme immunoassay-positive anti-interferon appeared in 6
0.7% of treated patients within 6 months of therapy; antiviral neutral
ization bioassay-positive anti-interferon appeared in 52.9% of these e
nzyme immunoassay-positive patients, and was associated with high enzy
me immunoassay reactivity and long-term persistence. Anti-interferon w
as detected in 75% of patients showing no response to interferon. Anti
bodies were also detected in three out of six patients who showed alan
ine aminotransferase normalization persisting up to the end of treatme
nt and in 8 out of 14 patients who showed an initial marked reduction
or even normalization of alanine aminotransferase, followed by reactiv
ation of liver damage during treatment. Interestingly, patients who be
came 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 reducti
on. These results seem to indicate that anti-interferon may interfere
with the biochemical response to interferon in some patients with chro
nic hepatitis C and that this interference is closely dependent on whe
ther anti-interferon appears before or after a response. (C) Journal o
f Hepatology.