Serum IP-10 profiles over time in treatment-experienced hepatitis C patients treated with a HCV NS3/4A protease inhibitor in combination with peginterferon and ribavirin
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1
Janssen Infectious Diseases, Belgium
Pre-treatment IP-10 (CXCL10) levels in hepatitis C virus (HCV) infected patients have been associated with treatment outcome upon peginterferon (pegIFN)/ribavirin (RBV) therapy, similar as IL28B genotype. Here we assessed on- and post-treatment changes in IP-10 serum levels in pegIFN/RBV treatment-experienced HCV-infected patients treated with pegIFNα-2a/RBV (n=65) or with a HCV NS3/4A protease inhibitor (PI) (simeprevir) together with pegIFNα-2a/RBV (n=195). Samples collected pre-treatment, at week 2 and 4 after treatment start, and 24 weeks after end of treatment were assessed.
Pre-treatment IP-10 levels were significantly lower in patients that relapsed during previous pegIFN/RBV treatment as compared to prior null and partial responders. After treatment start, serum IP-10 decreased over time. While serum IP-10 levels lower than at baseline were maintained in sustained virologic response (SVR) patients, in non-SVR patients the initial on-treatment IP-10 decline was reversed 24 weeks post-treatment. The treatment-induced IP-10 decrease versus baseline mirrored on-treatment HCV RNA declines and was observed already 2 weeks after initiation of PI/pegIFN/RBV therapy, whereas noticeable only after 4 weeks or later in subjects treated with pegIFN/RBV alone.
In line with earlier studies in treatment-naïve pegIFN/RBV treated patients, HCV RNA and IP-10 levels in treatment-experienced patients returned to baseline in patients who did not clear their HCV infection. Together with the faster decrease of IP-10 in patients treated with PI/pegIFN/RBV as compared to pegIFN/RBV alone, these findings suggest that on- and post-treatment changes in IP-10 levels in HCV-infected patients reflect alterations in the host immune response driven by the dynamics in viral load.
Keywords:
IP-10,
protease inhibitor,
Interferon-alpha,
CXCL10,
Antiviral treatment,
hepatitis C virus (HCV),
Ribavirin
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
Johansson
S,
Vijgen
L,
Talloen
W,
Beumont-Mauviel
M,
Peeters
M,
Lenz
O and
Aerssens
J
(2013). Serum IP-10 profiles over time in treatment-experienced hepatitis C patients treated with a HCV NS3/4A protease inhibitor in combination with peginterferon and ribavirin.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00832
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Received:
18 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Susanne Johansson, Janssen Infectious Diseases, Beerse, 2340, Belgium, sjohans2@its.jnj.com