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Reduction of HBV replication prolongs the early immunological response to IFNα therapy.
- Source :
-
Journal of hepatology [J Hepatol] 2014 Jan; Vol. 60 (1), pp. 54-61. Date of Electronic Publication: 2013 Aug 29. - Publication Year :
- 2014
-
Abstract
- Background & Aims: The interaction between HBV replication and immune modulatory effects mediated by IFNα therapy is not well understood. We characterized the impact of HBV DNA replication on the early IFNα-induced immunomodulatory mechanisms.<br />Methods: We interrogated the transcriptional, serum cytokine/chemokine and cellular immune profiles of 28 patients with HBeAg+ chronic HBV infection (CHB) randomly assigned to one of 4 treatment cohorts (untreated n=5, weekly dosing of 360 μg Pegasys [PegIFNα] n=11, daily dose of 300 mg Viread [tenofovir disoproxil fumarate, TDF] n=6, or a combination of both n=6). Samples were characterized at multiple early time points through day 14 of therapy, after which all patients were given standard of care (180 μg Pegasys injected subcutaneously, weekly).<br />Results: PegIFNα induced a distinct and rapid up-regulation of IFN signaling pathway that coincided with increase detection of distinct serum cytokines/chemokines (IL-15, IL-6, and CXCL-10) and the up-regulation of the frequency of proliferating NK and activated total CD8+ T cells. IFNα treatment alone did not result in rapid decay of HBV replication and was not able to restore the defective HBV-specific T cell response present in CHB patients. In addition, the IFNα immune-stimulatory effects diminished after the first dose, but this refractory effect was reduced in patients where HBV replication was simultaneously inhibited with TDF.<br />Conclusions: We present here the first comprehensive description of the early effects of IFNα treatment on immune and viral biomarkers in HBeAg+ CHB patients. Our results show that PegIFNα-induced innate immune activation directly benefits from the suppression of HBV replication.<br /> (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Adolescent
Adult
Cohort Studies
Hepatitis B, Chronic immunology
Hepatitis B, Chronic virology
Humans
Male
Middle Aged
Oligonucleotide Array Sequence Analysis
Recombinant Proteins therapeutic use
T-Lymphocytes immunology
Antiviral Agents therapeutic use
Hepatitis B virus physiology
Hepatitis B, Chronic drug therapy
Interferon-alpha therapeutic use
Polyethylene Glycols therapeutic use
Virus Replication drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1600-0641
- Volume :
- 60
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 23994382
- Full Text :
- https://doi.org/10.1016/j.jhep.2013.08.020