In:
Journal of Viral Hepatitis, Wiley, Vol. 22, No. 6 ( 2015-06), p. 524-534
Abstract:
Chronic infection with HCV is a public health problem with approximately 170 million people infected worldwide. Interferon alpha ( IFN α ) sensitivity in liver and IL 28B genotype has been identified as important determinants of HCV clearance in the setting of pegylated interferon/ribavirin treatment. Herein, we explored IFN α 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‐ STAT 1 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 α after priming and challenged with IFN α , with a subsequent decrease of phospho‐ STAT 1 and interferon‐stimulated genes. Furthermore, we show that CD 3+ T cells, but not monocytes, become desensitized after 4 weeks of treatment, with a significant decrease of phospho‐ STAT 1 after ex vivo IFN α stimulation. Finally, we identified baseline phospho‐ STAT 1 level in CD 3+ T cells as a potential biomarker of sustained virological response, regardless of the IL 28B genotype. In the upcoming costly era of IFN ‐sparing regimen, baseline IFN α 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.
Type of Medium:
Online Resource
ISSN:
1352-0504
,
1365-2893
DOI:
10.1111/jvh.2015.22.issue-6
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2007924-2
