title: HCV-specific T-cell response in relation to viral kinetics and treatment outcome (DITTO-HCV project).
abstract: OBJECTIVE
  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.
authors.affiliation: Azienda Ospedaliero-Universitaria Di Parma, Parma, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pilli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zerbini
authors.forename: Amalia
authors.initials: A
authors.lastname: Penna
authors.forename: Alessandra
authors.initials: A
authors.lastname: Orlandini
authors.forename: Esther
authors.initials: E
authors.lastname: Lukasiewicz
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Solko W
authors.initials: SW
authors.lastname: Schalm
authors.forename: Michael
authors.initials: M
authors.lastname: von Wagner
authors.forename: Georgios
authors.initials: G
authors.lastname: Germanidis
authors.forename: Yoav
authors.initials: Y
authors.lastname: Lurie
authors.forename: Juan I
authors.initials: JI
authors.lastname: Esteban
authors.forename: Bart L
authors.initials: BL
authors.lastname: Haagmans
authors.forename: Christophe
authors.initials: C
authors.lastname: Hezode
authors.forename: Martin
authors.initials: M
authors.lastname: Lagging
authors.forename: Francesco
authors.initials: F
authors.lastname: Negro
authors.forename: Yonit
authors.initials: Y
authors.lastname: Homburger
authors.forename: Avidan U
authors.initials: AU
authors.lastname: Neumann
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrari
authors.forename: Gabriele
authors.initials: G
authors.lastname: Missale
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005060:Europe; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D018963:Hepatitis Antigens / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000276:immunology; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000821:virology; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D018963:Hepatitis Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a