期刊
JOURNAL OF HEPATOLOGY
卷 59, 期 1, 页码 38-44出版社
ELSEVIER
DOI: 10.1016/j.jhep.2013.03.003
关键词
Hepatitis C virus; Natural killer cells; Interferon alpha; Antiviral therapy
资金
- Italian Ministry of Health (Ricerca Corrente, Fondazione IRCCS Policlinico San Matteo)
- Italian Ministry of Education, University and Research MiUR (Fondi di Investimento per la Ricerca di Base, FIRB, Protocollo) [RBAP10TPXK]
- COPEV Associazione per la Prevenzione e Cura dell'Epatite Virale Beatrice Vitiello ONLUS
Background & Aims: A substantial proportion of patients with chronic hepatitis C virus infection treated with pegylated interferon alpha/ribavirin fail to achieve sustained virological response (SVR). Since growing evidence suggests that innate immunity may influence treatment responses, we examined natural killer (NK) cell phenotypic and functional changes during standard antiviral therapy. Methods: Expression of several NK-cell regulatory molecules was evaluated by flow cytometry in 37 consecutive patients with chronic HCV infection at baseline and at different time points during and after discontinuation of treatment. Cytokine production was evaluated by intracellular staining. Cytolytic potential was assessed as degranulation and as antibody-dependent cytotoxicity. Results: Baseline frequencies of CD56(dim) NK cells and perforin content were significantly higher, whereas CD16 expression was lower in SVR vs. non-responder subjects. Analysis by linear regression for repeated measures during the first 12 weeks showed significantly increased frequencies of activated (CD69(+)) NK cells in rapid virological responders (RVR) and identified a typical NK cell profile associated with SVR, featuring higher NK perforin content, lower CD16 expression, and higher proportion of CD56(dim)/CD16(-) cells. Moreover, SVR patients displayed higher natural and antibody-dependent NK cell cytotoxicity. IL28B rs12979860 CC homozygosis was significantly associated with SVR, independently of NK-cell phenotype and function. Conclusions: Different NK-cell phenotypic and functional features, in patients with chronic hepatitis C treated with standard therapy, were observed between non-responder vs. SVR patients, suggesting a potential role of NK cells in the response to treatment. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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