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

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• 作者：Amalia Penna¹ ; ^&dagger ; ; Diletta Laccabue¹ ; ^&dagger ; ; Irene Libri¹ ; Tiziana Giuberti² ; Simona Schivazappa² ; Arianna Alfieri² ; Cristina Mori¹ ; Diana Canetti¹ ; Pietro Lampertico³ ; Mauro Viganò ; ³ ; Massimo Colombo³ ; Elisabetta Loggi⁴ ; Gabriele Missale¹ ; Carlo Ferrari² ; ^cafer@tin.it
• 关键词：HBV ; hepatitis B virus ; CHB ; chronic hepatitis B ; IFN ; interferon ; HbeAg ; hepatitis B e antigen ; SCR ; screening ; pre-TR ; pre-treatment ; BSL ; baseline ; HBsAg ; hepatitis B surface antigen ; tetramers ; tetrameric peptide-HLA Class I complexes ; MIX ; peptides m
• 刊名：Journal of Hepatology
• 出版年：2012
• 期刊代码：162_01688278
• 类别：med
• 出版时间：June, 2012
• 卷：56
• 期：6
• 页码：1239-1246
• 文件大小：783 K

摘要

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Background & Aims

The effect of IFN-伪 therapy on HBV-specific T-cell responses in HBeAg-negative, genotype D, chronic hepatitis B is largely undefined. Understanding to what extent IFN-伪 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 m>ex vivom> and after expansion m>in vitrom> in 15 patients with genotype D, HBeAg-negative chronic hepatitis B treated with peginterferon-伪-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

m>Ex vivom> IFN-纬 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 m>ex vivom> and m>in vitrom> analysis. PD-1/PD-L1 blockade showed a modest improvement of cytokine production in a total of 15%of T-cell lines.

Conclusions

IFN-伪 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 m>ex vivom> IFN-纬 production was associated with better chances to control HBV replication during therapy and represents a promising predictor of IFN efficacy.