HCV-Specific T-Cell Response in Relation to Viral Kinetics and Treatment Outcome (DITTO-HCV Project)

Massimo Pilli, Alessandro Zerbini, Amalia Penna, Alessandra Orlandini, Esther Lukasiewicz, Jean Michel Pawlotsky, Stefan Zeuzem, Solko W. Schalm, Michael von Wagner, Georgios Germanidis, Yoav Lurie, Juan I. Esteban, Bart L. Haagmans, Christophe Hezode, Martin Lagging, Francesco Negro, Yonit Homburger, Avidan U. Neumann, Carlo Ferrari, Gabriele Missale

Research output: Contribution to journalArticlepeer-review

Abstract

Background & Aims: The second slope of viral decline induced by interferon treatment has been suggested to be influenced mainly by the hepatitis C virus (HCV)-specific T-cell response; however, this hypothesis needs to be validated by results derived from experimental studies. Methods: To address this issue, the HCV-specific T-cell response of 32 genotype-1-infected patients of the 270 patients enrolled in the dynamically individualized treatment of hepatitis C infection and correlates of viral/host dynamics phase III, open-label, randomized, multicenter trial was studied in relation to viral kinetics and treatment outcome. Results: Greater proliferative responses by HCV-specific CD8 cells were found before treatment in patients with a fast viral decline and with a sustained viral response. However, no significant improvement of HCV-specific CD8 responses was observed in the first weeks of therapy in both rapid viral responder and non-rapid viral responder patients. A mild enhancement of proliferative T-cell responses and a partial restoration of the cytotoxic T-cell potential was expressed only late during treatment, likely favored by HCV clearance. Conclusions: Early restoration of an efficient T-cell response does not seem to be an essential requirement for a rapid viral decline in the first weeks of treatment. However, patients presenting a better HCV-specific CD8 cell proliferative potential at baseline are more likely to present a rapid and sustained viral response. Therefore, future treatment protocols should consider the development of strategies aimed at improving HCV-specific T-cell responses.

Original languageEnglish
Pages (from-to)1132-1143
Number of pages12
JournalGastroenterology
Volume133
Issue number4
DOIs
Publication statusPublished - Oct 2007

ASJC Scopus subject areas

  • Gastroenterology

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