Neutralizing antibodies to recombinant alpha-interferon and response to therapy in chronic hepatitis C virus infection.
Forty-seven patients with chronic hepatitis C were treated with recombinant interferon alpha-2a (rIFN alpha 2a) given subcutaneously in a standard dose of 3 MU thrice weekly for 12 months. Stored baseline sera and monthly samples during treatment were assayed for anti-interferon neutralizing antibodies using the antiviral neutralization bioassay against 5 IU of rIFN alpha 2a. During therapy, 15 of 47 patients (31.9%) developed detectable levels of neutralizing antibodies within 2-8 months after starting treatment. After 12 months of therapy, 26 of 32 antibody-negative patients (81.3%) showed normalization or marked reduction of ALT levels compared to 4 of 15 (26.6%) who developed anti-IFN neutralizing antibodies (p = 0.0009). Four patients demonstrated antiviral response during treatment even in the presence of low levels or late occurrence of neutralizing antibodies. Six of the seven patients who had disease reactivation after an initial response developed high titers of neutralizing antibodies. Our results suggest that reactivation of chronic hepatitis C before completion of therapy seems to be an obvious consequence of anti-IFN neutralizing antibody formation.
Milella
M
M
Institute of Infectious Diseases, University of Bari, Italy.
Antonelli
G
G
Santantonio
T
T
Currenti
M
M
Monno
L
L
Mariano
N
N
Angarano
G
G
Dianzani
F
F
Pastore
G
G
D000410:Alanine Transaminase / Q000097:blood; D000906:Antibodies / Q000032:analysis*; D000917:Antibody Formation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006526:Hepatitis C / Q000276:immunology / Q000628:therapy*; D006521:Hepatitis, Chronic / Q000276:immunology / Q000628:therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000276:immunology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D011994:Recombinant Proteins; D012189:Retrospective Studies
D000906:Antibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000410:Alanine Transaminase