HCV-specific T-cell response in relation to viral kinetics and treatment outcome (DITTO-HCV project)

Gastroenterology. 2007 Oct;133(4):1132-43. doi: 10.1053/j.gastro.2007.06.059. Epub 2007 Jul 3.


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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / virology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Drug Therapy, Combination
  • Enzyme-Linked Immunosorbent Assay
  • Europe
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepacivirus / growth & development
  • Hepatitis Antigens / genetics
  • Hepatitis Antigens / immunology
  • Hepatitis C / diagnosis
  • Hepatitis C / drug therapy*
  • Hepatitis C / immunology
  • Humans
  • Immunity, Cellular / drug effects*
  • Interferon alpha-2
  • Interferon-alpha / pharmacology
  • Interferon-alpha / therapeutic use*
  • Kinetics
  • Lymphocyte Activation / drug effects
  • Polyethylene Glycols / pharmacology
  • Polyethylene Glycols / therapeutic use*
  • RNA, Viral / blood
  • Recombinant Proteins / immunology
  • Ribavirin / pharmacology
  • Ribavirin / therapeutic use*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / virology
  • Treatment Outcome
  • Virus Replication / drug effects*


  • Antiviral Agents
  • Hepatitis Antigens
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a