Neutralizing antibodies to interferon alpha and circulating Interferon in chronic hepatitis C patients non-responding to pegylated interferon plus ribavirin re-treated by Peg-Interferon alpha-2a and ribavirin (ANRS HC16 GAMMATRI substudy*)

Philippe Halfon , Sophie Pérusat , Marc Bourlière , Jean-Pierre Bronowicki , Pascale Trimoulet (1) , Yves Behnamou , Vincent Leroy , Patrick Marcellin (2) , Juliette Foucher (1) , Guillaume Pénaranda (3) , Geneviève Chene , Patrice Couzigou (1)

1 Service de virologie et d'immunologie biologique
2 Service d'hépatologie
3 Laboratoire Alphabio

Statement of the problem A lack of antiviral response in chronic hepatitis C patients treated by pegylated (PEG)-interferon (IFN) α-2a + ribavirin (RIBA) might be explained by neutralizing antibodies to IFN α-2a. The aim 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. Methods of study Non-responders to a first-line treatment were included to receive PEG IFN α-2a + RIBA for 48 weeks. HCV RNA was measured at week 12 using TaqMan Roche. IFN levels and neutralizing antibodies to IFN α-2a were retrospectively measured on stored sera at baseline, week 4, and 12, using a quantitative sandwich ELISA for neutralizing antibodies to IFN α-2a. Results Twenty-three patients were non-responders and 19 patients were responders at week 12 of the initial phase of second-line treatment. Non-responders and responders did not statistically differ. 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 1652 (90.8- 5000); 84.5 (3.3- 277.4), 1407.4 (120.2- 2443.4), and 1620.1 (120.2- 2287.1) respectively. Conclusions Among non-selected consecutive non-responders 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.

Mots clés: Medicine

Philippe Halfon, Sophie Pérusat, Marc Bourlière, Jean-Pierre Bronowicki, Pascale Trimoulet, et al.. Neutralizing antibodies to interferon alpha and circulating Interferon in chronic hepatitis C patients non-responding to pegylated interferon plus ribavirin re-treated by Peg-Interferon alpha-2a and ribavirin (ANRS HC16 GAMMATRI substudy*). Journal of Medical Virology, 2010, 82 (12), pp.2027. ⟨10.1002/jmv.21909⟩. ⟨hal-00589434⟩