Abstract:
:Pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV) treatment fails to achieve a sustained virological response (SVR) in approximately 20-50% of patients with chronic hepatitis C virus (HCV) infection. We assessed the contribution of an anti-IFN-α neutralizing antibody (NAb) on the nonresponse to treatment. NAbs were detected using an antiviral assay that assessed the neutralizing effects of serum samples against IFN. Serum samples were obtained at the end of the treatment and evaluated for the presence of NAbs using recombinant IFN-α as a standard. We studied 129 PEG-IFN-α/RBV-treated patients. In the 82 end-of-treatment responders, no NAbs were detected. Of the 47 patients who did not respond, seven (15%) were positive for NAbs. We also examined an additional 83 patients who had not responded to PEG-IFN-α treatment, and detected 12 with NAbs. Patients with good IFN-responsive characteristics, including HCV genotype 2/3 and major allele homozygotes for interleukin-28B, were included in the 19 patients with NAbs. No NAbs interfered with the antiviral activity of natural human IFN-β (nIFN-β) and re-treatement of patients with NAbs with nIFN-β/RBV achieved SVR. Our analyses revealed that the emergence of anti-IFN-α NAbs was a candidate causal factor of PEG-IFN-α-treatment failure. Therefore, these antibodies should be assayed in patients who do not respond to PEG-IFN-α therapy, and if detected, other effective treatments, i.e., medications that are not neutralized by anti-IFN-α NAbs, should be considered.
journal_name
J Viral Hepatjournal_title
Journal of viral hepatitisauthors
Matsuda F,Torii Y,Enomoto H,Kuga C,Aizawa N,Iwata Y,Saito M,Imanishi H,Shimomura S,Nakamura H,Tanaka H,Iijima H,Tsutsui H,Tanaka Y,Nishiguchi Sdoi
10.1111/j.1365-2893.2012.01598.xsubject
Has Abstractpub_date
2012-10-01 00:00:00pages
694-703issue
10eissn
1352-0504issn
1365-2893journal_volume
19pub_type
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