TY - JOUR
T1 - Immune responses in DAA treated chronic hepatitis C patients with and without prior RG-101 dosing
AU - van der Ree, Meike H.
AU - Stelma, Femke
AU - Willemse, Sophie B.
AU - Brown, Anthony
AU - Swadling, Leo
AU - van der Valk, Marc
AU - Sinnige, Marjan J.
AU - van Nuenen, Ad C.
AU - de Vree, J. Marleen L.
AU - Klenerman, Paul
AU - Barnes, Eleanor
AU - Kootstra, Neeltje A.
AU - Reesink, Hendrik W.
PY - 2017
Y1 - 2017
N2 - Background&aims: With the introduction of DAA's, the majority of treated chronic hepatitis C patients (CHC) achieve a viral cure. The exact mechanisms by which the virus is cleared after successful therapy, is still unknown. The aim was to assess the role of the immune system and miRNA levels in acquiring a sustained virological response after DAA treatment in CHC patients with and without prior RG-101 (antimiR-122) dosing. Methods: In this multicenter, investigator-initiated study, 29 patients with hepatitis C virus (HCV) genotype 1 (n = 11), 3 (n = 17), or 4 (n = 1) infection were treated with sofosbuvir and daclatasvir +/- ribavirin. 18 patients were previously treated with RG-101. IP-10 levels were measured by ELISA. Ex vivo HCV-specific T cell responses were quantified in IFN-gamma-ELISpot assays. Plasma levels of miR-122 were measured by qPCR. Results: All patients had an SVR12. IP-10 levels rapidly declined during treatment, but were still elevated 24 weeks after treatment as compared to healthy controls (median 53.82 and 39.4 pg/mL, p = 0.02). Functional IFN-gamma HCV-specific T cell responses did not change by week 12 of follow-up (77.5 versus 125 SFU/10(6) PBMC, p = 0.46). At follow-up week 12, there was no difference in plasma miR-122 levels between healthy controls and patients with and without prior RG-101 dosing. Conclusions: Our data shows that successful treatment of CHC patients with and without prior RG-101 dosing results in reduction of broad immune activation, and normalisation of miR-122 levels (EudraCT: 2014-002808-25). (C) 2017 Elsevier B.V. All rights reserved
AB - Background&aims: With the introduction of DAA's, the majority of treated chronic hepatitis C patients (CHC) achieve a viral cure. The exact mechanisms by which the virus is cleared after successful therapy, is still unknown. The aim was to assess the role of the immune system and miRNA levels in acquiring a sustained virological response after DAA treatment in CHC patients with and without prior RG-101 (antimiR-122) dosing. Methods: In this multicenter, investigator-initiated study, 29 patients with hepatitis C virus (HCV) genotype 1 (n = 11), 3 (n = 17), or 4 (n = 1) infection were treated with sofosbuvir and daclatasvir +/- ribavirin. 18 patients were previously treated with RG-101. IP-10 levels were measured by ELISA. Ex vivo HCV-specific T cell responses were quantified in IFN-gamma-ELISpot assays. Plasma levels of miR-122 were measured by qPCR. Results: All patients had an SVR12. IP-10 levels rapidly declined during treatment, but were still elevated 24 weeks after treatment as compared to healthy controls (median 53.82 and 39.4 pg/mL, p = 0.02). Functional IFN-gamma HCV-specific T cell responses did not change by week 12 of follow-up (77.5 versus 125 SFU/10(6) PBMC, p = 0.46). At follow-up week 12, there was no difference in plasma miR-122 levels between healthy controls and patients with and without prior RG-101 dosing. Conclusions: Our data shows that successful treatment of CHC patients with and without prior RG-101 dosing results in reduction of broad immune activation, and normalisation of miR-122 levels (EudraCT: 2014-002808-25). (C) 2017 Elsevier B.V. All rights reserved
U2 - https://doi.org/10.1016/j.antiviral.2017.08.016
DO - https://doi.org/10.1016/j.antiviral.2017.08.016
M3 - Article
C2 - 28844749
SN - 0166-3542
VL - 146
SP - 139
EP - 145
JO - Antiviral Research
JF - Antiviral Research
ER -