Background & Aims: The effect of IFN-α therapy on HBV-specific T-cell responses in HBeAg-negative, genotype D, chronic hepatitis B is largely undefined. Understanding to what extent IFN-α can modulate HBV-specific T-cells is important to define strategies to optimize IFN efficacy and to identify immunological parameters to predict response to therapy. Methods: HBV-specific T-cell responses were analyzed longitudinally ex vivo and after expansion in vitro in 15 patients with genotype D, HBeAg-negative chronic hepatitis B treated with peginterferon-α-2a. HBV proteins and synthetic peptides were used to stimulate T-cell responses. Analysis of the CD4 and CD8 T-cell functions was performed by ELISPOT, intracellular cytokine and tetramer staining. The effect of anti-PD-L1 on T-cell functions was also analyzed. Results: Ex vivo IFN-γ production by total HBV-specific T-cells was significantly greater before therapy in patients who showed HBV DNA <50 IU/ml at weeks 24 and/or 48 of therapy. No significant improvement of T-cell proliferation, Th1 cytokine production and cytotoxicity was observed during IFN therapy by both ex vivo and in vitro analysis. PD-1/PD-L1 blockade showed a modest improvement of cytokine production in a total of 15% of T-cell lines. Conclusions: IFN-α did not improve peripheral blood HBV-specific T-cell responses in the first 24 weeks of treatment, consistent either with a predominant antiviral/antiproliferative effect or with an immunomodulatory activity on other arms of the immune system which were not analyzed in our study. A better pre-treatment ex vivo IFN-γ production was associated with better chances to control HBV replication during therapy and represents a promising predictor of IFN efficacy. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Peginterferon-α does not improve early peripheral blood HBV-specific T-cell responses in HBeAg-negative chronic hepatitis / Penna, Amalia; Laccabue, Diletta; Libri, Irene; Giuberti, Tiziana; Schivazappa, Simona; Alfieri, Arianna; Mori, Cristina; Canetti, Diana; Lampertico, Pietro; Viganò, Mauro; Colombo, Massimo; Loggi, Elisabetta; Missale, Gabriele; Ferrari, Carlo. - In: JOURNAL OF HEPATOLOGY. - ISSN 0168-8278. - 56:6(2012), pp. 1239-1246. [10.1016/j.jhep.2011.12.032]

Peginterferon-α does not improve early peripheral blood HBV-specific T-cell responses in HBeAg-negative chronic hepatitis

Missale, Gabriele;FERRARI, Carlo
2012-01-01

Abstract

Background & Aims: The effect of IFN-α therapy on HBV-specific T-cell responses in HBeAg-negative, genotype D, chronic hepatitis B is largely undefined. Understanding to what extent IFN-α can modulate HBV-specific T-cells is important to define strategies to optimize IFN efficacy and to identify immunological parameters to predict response to therapy. Methods: HBV-specific T-cell responses were analyzed longitudinally ex vivo and after expansion in vitro in 15 patients with genotype D, HBeAg-negative chronic hepatitis B treated with peginterferon-α-2a. HBV proteins and synthetic peptides were used to stimulate T-cell responses. Analysis of the CD4 and CD8 T-cell functions was performed by ELISPOT, intracellular cytokine and tetramer staining. The effect of anti-PD-L1 on T-cell functions was also analyzed. Results: Ex vivo IFN-γ production by total HBV-specific T-cells was significantly greater before therapy in patients who showed HBV DNA <50 IU/ml at weeks 24 and/or 48 of therapy. No significant improvement of T-cell proliferation, Th1 cytokine production and cytotoxicity was observed during IFN therapy by both ex vivo and in vitro analysis. PD-1/PD-L1 blockade showed a modest improvement of cytokine production in a total of 15% of T-cell lines. Conclusions: IFN-α did not improve peripheral blood HBV-specific T-cell responses in the first 24 weeks of treatment, consistent either with a predominant antiviral/antiproliferative effect or with an immunomodulatory activity on other arms of the immune system which were not analyzed in our study. A better pre-treatment ex vivo IFN-γ production was associated with better chances to control HBV replication during therapy and represents a promising predictor of IFN efficacy. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
2012
Peginterferon-α does not improve early peripheral blood HBV-specific T-cell responses in HBeAg-negative chronic hepatitis / Penna, Amalia; Laccabue, Diletta; Libri, Irene; Giuberti, Tiziana; Schivazappa, Simona; Alfieri, Arianna; Mori, Cristina; Canetti, Diana; Lampertico, Pietro; Viganò, Mauro; Colombo, Massimo; Loggi, Elisabetta; Missale, Gabriele; Ferrari, Carlo. - In: JOURNAL OF HEPATOLOGY. - ISSN 0168-8278. - 56:6(2012), pp. 1239-1246. [10.1016/j.jhep.2011.12.032]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2814738
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