T-cell homeostasis in chronic HCV-infected patients treated with interferon and ribavirin or an interferon-free regimen

APMIS. 2015 Oct;123(10):903-11. doi: 10.1111/apm.12429. Epub 2015 Aug 17.

Abstract

Direct-acting antiviral has replaced pegylated interferon-α and ribavirin-based treatment in the treatment of chronic hepatitis C virus (HCV) infection. While interferon-α is immune modulating and causes lymphopenia, interferon-free regimens seem to be well-tolerated. This study aimed to compare T-cell homeostasis before, during, and after HCV treatment with or without interferon-α in patients with chronic HCV infection. A total of 20 patients with chronic HCV infection were treated with pegylated interferon-α and ribavirin, and six patients were treated with an interferon-free regimen. All patients were treated for a minimum of 12 weeks. Interferon-α treatment caused an increase in the density of the receptor for IL-7 (IL-7Rα) during treatment, while interferon-free regimens caused a decrease in IL-7Rα density. After a sustained viral response, proportions of IL-7Rα+ T cells and IL-7Rα density decreased compared to prior treatment values. Finally, a proportion of CD8+ effector memory was lower while proportion of apoptotic T cells was higher after sustained virologic response compared to prior treatment. Despite lymphopenia during interferon, alterations in T-cell homeostasis during treatment were relatively similar in patients receiving interferon-based treatment and in patients receiving interferon-free treatment, and alterations during and after treatment seem to illustrate a reduced need for high levels of T cells aimed at controlling infection.

Keywords: Direct-acting antivirals; HCV treatment; Interleukin-7 receptor; T cells; interferon-α.

MeSH terms

  • Adult
  • Aged
  • Amides
  • Antiviral Agents / therapeutic use
  • Apoptosis / immunology
  • Benzofurans / therapeutic use
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Carbamates
  • Cyclopropanes
  • Drug Therapy, Combination
  • Female
  • Hepacivirus / immunology
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / virology
  • Humans
  • Imidazoles / therapeutic use
  • Interferon-alpha / therapeutic use*
  • Interleukin-7 Receptor alpha Subunit / metabolism*
  • Lipopolysaccharides / analysis
  • Lymphocyte Count
  • Lymphopenia / chemically induced
  • Male
  • Middle Aged
  • Oligopeptides / therapeutic use
  • Polyethylene Glycols / therapeutic use*
  • Proline / analogs & derivatives
  • Proline / therapeutic use
  • Prospective Studies
  • Quinoxalines / therapeutic use
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use*
  • Sulfonamides

Substances

  • Amides
  • Antiviral Agents
  • Benzofurans
  • Carbamates
  • Cyclopropanes
  • Imidazoles
  • Interferon-alpha
  • Interleukin-7 Receptor alpha Subunit
  • Lipopolysaccharides
  • Oligopeptides
  • Quinoxalines
  • Recombinant Proteins
  • Sulfonamides
  • Polyethylene Glycols
  • Ribavirin
  • grazoprevir
  • elbasvir
  • telaprevir
  • N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide
  • Proline
  • peginterferon alfa-2a