T-cell homeostasis in chronic HCV-infected patients treated with interferon and ribavirin or an interferon-free regimen.
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.
Viro-Immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.|Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Hans Jakob
HJ
Hartling
Viro-Immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.|Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Carsten
C
Birch
Viro-Immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.|Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Julie C
JC
Gaardbo
Viro-Immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.|Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Malene
M
Hove
Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.
Marius
M
Trøseid
Department of Hepatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Mette Rye
MR
Clausen
Viro-Immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Jan
J
Gerstoft
Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Henrik
H
Ullum
Viro-Immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Susanne Dam
SD
Nielsen
D000328:Adult; D000368:Aged; D000577:Amides; D000998:Antiviral Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000276:immunology; D001572:Benzofurans / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002219:Carbamates; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use*; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000032:analysis; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011392:Proline / Q000031:analogs & derivatives / Q000627:therapeutic use; D011446:Prospective Studies; D011810:Quinoxalines / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D013449:Sulfonamides; D047029:Lactams, Macrocyclic
D000577:Amides; D000998:Antiviral Agents; D001572:Benzofurans; D002219:Carbamates; D003521:Cyclopropanes; D007093:Imidazoles; D016898:Interferon-alpha; D053699:Interleukin-7 Receptor alpha Subunit; D008070:Lipopolysaccharides; D009842:Oligopeptides; D011092:Polyethylene Glycols; D011392:Proline; D011810:Quinoxalines; D011994:Recombinant Proteins; D012254:Ribavirin; D013449:Sulfonamides; C578009:grazoprevir; D047029:Lactams, Macrocyclic; C000589335:elbasvir; C486464:telaprevir; C512204: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; C100416:peginterferon alfa-2a
Direct-acting antivirals; HCV treatment; Interleukin-7 receptor; T cells; interferon-α