van der Ree, MH;
Stelma, F;
Willemse, SB;
Brown, A;
Swadling, L;
van der Valk, M;
Sinnige, MJ;
... Reesink, HW; + view all
(2017)
Immune responses in DAA treated chronic hepatitis C patients with and without prior RG-101 dosing.
Antiviral Research
, 146
pp. 139-145.
10.1016/j.antiviral.2017.08.016.
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Abstract
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 ¼ 11), 3 (n ¼ 17), or 4 (n ¼ 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-g-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 ¼ 0.02). Functional IFN-g HCV-specific T cell responses did not change by week 12 of follow-up (77.5 versus 125 SFU/106 PBMC, p ¼ 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). Trial registration: EudraCT: 2014-002808-25.
| Type: | Article |
|---|---|
| Title: | Immune responses in DAA treated chronic hepatitis C patients with and without prior RG-101 dosing |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.antiviral.2017.08.016 |
| Publisher version: | https://doi.org/10.1016/j.antiviral.2017.08.016 |
| Language: | English |
| Additional information: | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Pharmacology & Pharmacy, Virology, Chronic hepatitis C, DAA treatment, Immune response, miRNA-122, HUMAN HEPATOCELLULAR-CARCINOMA, DACLATASVIR PLUS SOFOSBUVIR, DIRECT-ACTING ANTIVIRALS, INTERFERON-FREE THERAPY, ADVANCED LIVER-DISEASE, VIRUS GENOTYPE 3, T-CELLS, NATURAL-KILLER, PHASE-III, CYCLIN G1 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10112380 |
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