Natural killer cell dynamic profile is associated with treatment outcome in patients with chronic HCV infection

Barbara Oliviero, Dalila Mele, Elisabetta Degasperi, Alessio Aghemo, Eleonora Cremonesi, Maria Grazia Rumi, Carmine Tinelli, Stefania Varchetta, Stefania Mantovani, Massimo Colombo, Mario U. Mondelli

Research output: Contribution to journalArticlepeer-review


Background & Aims A substantial proportion of patients with chronic hepatitis C virus infection treated with pegylated interferon α/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 CD56dim/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.

Original languageEnglish
Pages (from-to)38-44
Number of pages7
JournalJournal of Hepatology
Issue number1
Publication statusPublished - Jul 2013


  • Antiviral therapy
  • Hepatitis C virus
  • Interferon alpha
  • Natural killer cells

ASJC Scopus subject areas

  • Hepatology


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