Hepatitis C virus-specific cytotoxic T cell response restoration after treatment-induced hepatitis C virus control

Table 1 Summary of published works about hepatitis C virus-specific cytotoxic T lymphocyte during anti-hepatitis C virus treatment pointing-out the data in favor and against hepatitis C virus-specific cytotoxic T lymphocyte response restoration either during or after treatment

Ref.	Year	Treatment	Samples	CTL visualization	In favor	Against
Martin et al[89]	2014	DAA	Frozen PBMC	Tetramer staining	Restoration of HCV-specific CTL response during treatment in SVR cases
Larrubia et al[60]	2013	PEG-IFN/RBV	Fresh PBMC	Pentamer staining	HCV-CTLs detection at week 12 of treatment correlates with infection resolution Detection of PD-1low HCV-specific CTLs after treatment correlates with SVR
Humphreys et al[82]	2012	PEG-IFN/RBV	Frozen PBMC	γ-IFN ELISPOT assay		Treatment induced genotype-3a viral clearance is not associated with an enhancement of antiviral T cell response
Tatsumi et al[78]	2011	PEG-IFN/RBV	Fresh PBMC	γ-IFN ELISPOT assay	HCV-specific CTL frequency increase between base-line and treatment week 4 was observed in SVR but not in non SVR patients
Barnes et al[83]	2009	PEG-IFN/RBV	Frozen PBMC	γ-IFN and IL-2 ELISPOT assay		Not enhanced specific T cell response during high dose IFNa therapy was reported
Caetano et al[77]	2008	PEG-IFN/RBV	Fresh PBMC	Pentamer staining	Chronically infected patients who responded to treatment showed a higher HCV-specific CTL frequency than non-responders during and post-treatment Terminally differentiated effector cells increased more rapidly in responders, and their frequency was always higher than in non-responder patients
Golden-Mason et al[85]	2008	PEG-IFN/RBV	PBMC	Pentamer staining	Patients with sustained viral response showed a decrease in PD-1 expression on HCV-specific CTLs after therapy completion
Badr et al[73]	2008	PEG-IFN	Frozen PBMC	Tetramer staining	Early therapeutic intervention during the acute phase of HCV infection reconstituted a long-lived polyfunctional memory T cell response
Pilli et al[81]	2007	PEG-IFN/RBV	Frozen PBMC	γIFN ELISPOT assay and tetramer staining		No significant correlation between HCV-specific CTL kinetics and viral decay during treatment
Morishima et al[75]	2003	IFN/RBV	Fresh PBMC	Chromium-51 release assay	Subjects who had completed the treatment and had undetectable HCV RNA levels after therapy had a detectable HCV-specific CTL response more frequently than those who were viraemic
Vertuani et al[76]	2002	IFN	Fresh PBMC	Chromium-51 release assay	Increase in the intensity of HCV epitope recognition by HCV-specific CTL after 1 to 5 m of treatment
Barnes et al[79]	2002	IFN/RBV	Frozen PBMC	γIFN ELISPOT assay		T cell responses induced during high dose of IFNa treatment appear not to influence the virological outcome

DAA: Direct acting anti-viral; IFN: Interferon-α2; RBV: Ribavirin; PBMC: Peripheral blood mononuclear cells; γ-IFN: Gamma-interferon; SVR: Sustained viral response.