Background & Aims
Chronic hepatitis C virus (HCV) infection is characterised by a failure of virus-specific
CD8+ T cells that is mainly caused by viral escape and T cell exhaustion. Constant
antigen stimulation has been suggested to contribute to HCV-specific CD8+ T cell exhaustion.
However, IFN-based therapies failed to recover HCV-specific CD8+ T cell function suggesting
that the damage to CD8+ T cells may be permanent even after antigen removal. It was
therefore the objective of this study to analyse the impact of inhibition of ongoing
viral replication by IFN-free therapy with direct acting antivirals (DAA) on the phenotype
and function of HCV-specific CD8+ T cells.
Methods
Virus-specific CD8+ T cells obtained from a patient cohort of 51 previously untreated
chronically infected patients undergoing IFN-free therapy with a combination of faldaprevir
(a protease inhibitor) and deleobuvir (a non-nucleoside polymerase inhibitor) with
or without ribavirin were analysed ex vivo and after in vitro expansion at baseline, wk4, wk12, and after treatment.
Results
Our results show the rapid restoration of proliferative HCV-specific CD8+ T cells
in the majority of patients with SVR12 within 4 weeks of therapy suggesting that IFN-free therapy mediated antigen removal may restore
CD8+ T cell function.
Conclusions
This study indicates a specific restoration of proliferative HCV-specific CD8+ T cells
under IFN-free therapy. This is in contrast to PegIFN-based therapies that have been
shown not to restore T cell function during and after chronic infection.
Keywords
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Article info
Publication history
Published online: June 03, 2014
Accepted:
May 26,
2014
Received in revised form:
May 26,
2014
Received:
May 12,
2014
See Editorial, pages 459–461Identification
Copyright
© 2014 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
