Hepatitis C Virus-Specific T-cell Reactivity During Interferon and Ribavirin Treatment in Chronic Hepatitis C

Gastroenterology. 2000 Feb;118(2):346-55. doi: 10.1016/s0016-5085(00)70217-4.

Abstract

Background & aims: The role of virus-specific T-helper lymphocyte reactivity in determining the therapeutic response in chronic hepatitis C virus (HCV) infection is not fully understood.

Methods: We studied CD4(+) T lymphocyte proliferation together with interferon (IFN)-gamma and interleukin (IL)-10 production from peripheral blood mononuclear cells in response to 4 HCV antigens (core, NS3, NS4, and NS5) in 25 patients with chronic hepatitis C undergoing antiviral therapy with IFN alone or in combination with ribavirin, prospectively, before, during, and after treatment.

Results: HCV-specific T-cell reactivity was uncommon at baseline but increased markedly during antiviral therapy, peaking around treatment weeks 4-8. Resolution of hepatitis C viremia was significantly more likely in patients who developed HCV-specific T-cell proliferation with increased IFN-gamma production. The main difference in T-cell reactivity of patients treated with IFN plus ribavirin was a significantly lower production of IL-10, whereas lymphocyte proliferation was similar to that in patients receiving IFN monotherapy.

Conclusions: Treatment-induced control of hepatitis C viremia is associated with the development of HCV-specific T-cell responses with enhanced IFN-gamma and low IL-10 production. The greater efficacy of combination therapy with IFN-alpha plus ribavirin may be related to its ability to suppress HCV-specific IL-10 production.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Antiviral Agents / therapeutic use*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • Cohort Studies
  • Female
  • Genotype
  • Hepacivirus / genetics
  • Hepacivirus / immunology*
  • Hepacivirus / isolation & purification
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / immunology*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / biosynthesis
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Recombinant Proteins
  • Ribavirin / therapeutic use*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology
  • Viral Load

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Interleukin-10
  • Ribavirin
  • Interferon-gamma
  • Alanine Transaminase