title: Neutralizing antibodies to interferon-α and circulating interferon in patients with chronic hepatitis C non-responding to pegylated interferon plus ribavirin re-treated by pegylated interferon-α-2a and ribavirin (ANRS HC16 GAMMATRI substudy).
abstract: A lack of antiviral response in patients with chronic hepatitis C treated with pegylated (PEG)-interferon (IFN)-α-2a + ribavirin (RIBA) may be explained by neutralizing antibodies to IFN-α-2a. The aim of this study was to assess neutralizing antibodies to IFN-α-2a and IFN levels in non-responder patients who were re-treated by PEG IFN-α-2a and RIBA for 12 weeks. Non-responders to a first-line treatment of PEG IFN-α-2a + RIBA were included for treatment with PEG IFN-α-2a (180 µg/week) + RIBA (1,000 mg/day if <75 kg, 1,200 mg otherwise) for 48 weeks. HCV RNA was measured at week 12. IFN levels and neutralizing antibodies to IFN-α-2a were measured retrospectively on stored sera at baseline and weeks 4 and 12, using a quantitative sandwich ELISA for neutralizing antibodies to IFN-α-2a. Twenty-three patients were non-responders and 19 patients were responders at week 12 of the initial phase of the second-line treatment. Non-responders and responders did not differ statistically: baseline age (median age 47 vs. 50 years), HCV RNA (median 6.8 vs. 6.4 log(10) copies/ml), gender (70% vs. 73% males), genotype (genotype 1: 91% vs. 80%). The median IFN-α-2a levels (pg/ml) at weeks 0, 4, and 12 (interquartile range) did not differ between the 19 responders to initial phase of second-line treatment and the 23 non-responders: <3.3 (<3.3-371.4), 1457.3 (106.8-3284.8), and 1,652 (90.8-5,000); 84.5 (3.3-277.4), 1407.4 (120.2-2443.4), and 1620.1 (120.2-2287.1), respectively. Among non-selected consecutive non-responder patients, re-treatment with PEG IFN-α-2a + RIBA is associated with virological response regardless of the presence of antibody-mediated resistance to conventional IFN treatment.
authors.affiliation: Alphabio Laboratory, Ambroise Paré Hospital, Marseille, France. philippe.halfon@alphabio.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Halfon
authors.forename: Sophie
authors.initials: S
authors.lastname: Pérusat
authors.forename: Marc
authors.initials: M
authors.lastname: Bourlière
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.forename: Pascale
authors.initials: P
authors.lastname: Trimoulet
authors.forename: Yves
authors.initials: Y
authors.lastname: Benhamou
authors.forename: Vincent
authors.initials: V
authors.lastname: Leroy
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.forename: Juliette
authors.initials: J
authors.lastname: Foucher
authors.forename: Guillaume
authors.initials: G
authors.lastname: Penaranda
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chêne
authors.forename: Patrice
authors.initials: P
authors.lastname: Couzigou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000097:blood* / Q000276:immunology; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000097:blood* / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D007371:Interferon-gamma / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D007371:Interferon-gamma; C100416:peginterferon alfa-2a