Baseline sensitivity of T cells to alpha‐IFN correlates with sustained virological response to IFN‐based triple therapy in HCV infection. Issue 6 (10th November 2014)

• Record Type: Journal Article
• Authors: Sultanik, P.‐S.; Casrouge, A.; Alanio, C.; Mottez, E.; Rosa‐Hézode, I.; Hézode, C.; Renard, P.; Bousquet, L.; Pellet, P.; Uzé, G.; Pol, S.; Albert, M. L.; Mallet, V.
• Is Part Of: Journal of viral hepatitis. Volume 22:Issue 6(2015)
• Page Start: 524
• Page End: 534
• Publication Date: 2014-11-10
• Subjects: Hepatitis, Viral -- Periodicals; Hepatitis, Viral, Animal; Hepatitis, Viral, Human; 616.3623
• DOI: 10.1111/jvh.12355
• Languages: English
• ISSNs: 1352-0504

Abstract

<abstract abstract-type="main" id="jvh12355-abs-0001"> <title>Summary</title> <p>Chronic infection with HCV is a public health problem with approximately 170 million people infected worldwide. Interferon alpha (IFN<italic>α</italic>) sensitivity in liver and <italic>IL28B</italic> genotype has been identified as important determinants of HCV clearance in the setting of pegylated interferon/ribavirin treatment. Herein, we explored IFN<italic>α</italic> sensitivity in PBMC from 21 healthy donors and 21 HCV‐infected patients treated with pegylated interferon/ribavirin and HCV nonstructural protein‐3 inhibitors (i.e. telaprevir/boceprevir). We explored phospho‐STAT1 level as read‐out for IFN signalling pathway activation in PBMC, T cells and monocytes and correlated results with virological response. We found that PBMC from healthy donors are desensitized to IFN<italic>α</italic> after priming and challenged with IFN<italic>α</italic>, with a subsequent decrease of phospho‐STAT1 and interferon‐stimulated genes. Furthermore, we show that CD3+ T cells, but not monocytes, become desensitized after 4 weeks of treatment, with a significant decrease of phospho‐STAT1 after <italic>ex vivo </italic>IFN<italic>α</italic> stimulation. Finally, we identified baseline phospho‐STAT1 level in CD3+ T cells as a potential biomarker of sustained virological response, regardless of the <italic>IL28B</italic> genotype. In the upcoming costly era of IFN‐sparing regimen, baseline IFN<italic>α</italic> sensitivity could act as biomarker to define cost‐effectiveness strategies of treatment by identifying patients who will or will not respond to IFN‐based treatments.</p> </abstract>