title: Sustained virological response to peginterferon plus ribavirin in chronic hepatitis C genotype 1 patients is associated with a persistent Th1 immune response.
abstract: BACKGROUND
  An impairment of cellular immune response may contribute to the persistency of hepatitis C virus infection.
  
  
  OBJECTIVE
  To analyse the Th1/Th2 cytokine profile in peripheral blood CD4(+) and CD8(+) T cells from patients with chronic hepatitis C (CHC) during treatment with pegylated interferon-alpha2a plus ribavirin and to correlate the Th1/Th2 balance with virological response (SVR).
  
  
  METHODS
  Prospective longitudinal study: 44 naïve genotype 1 CHC patients received PEG-IFNalpha2a plus ribavirin for 48 weeks: 26 (59.1%) achieved a SVR, 13 relapsed (29.5%) and 5 (11.4%) were non-responders. Sixteen healthy controls were analysed. The production of IL-4, IFNgamma and TNFalpha by CD4(+) and CD8(+) T cells was measured using flow cytometry, both in resting and phorbol-ester-stimulated cells.
  
  
  RESULTS
  First three months of treatment: the synthesis of TNFalpha by phorbol-ester-stimulated-CD4(+) T cells was higher in patients with SVR (P < 0.01). At the end of treatment, SVR was associated with higher intracellular expression of IFNgamma by stimulated-CD4(+) and CD8(+) T cells (P < 0.05). At the end of follow-up, a higher intracellular expression of IFNgamma by CD4(+) T cells was associated with a SVR.
  
  
  CONCLUSIONS
  A Th1-type immune response was associated with achievement of a SVR, as indicated by the persistent elevation of intracellular IFNgamma and TNFalpha.
authors.affiliation: Gastroenterology and Hepatology Service, Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Trapero-Marugán
authors.forename: L
authors.initials: L
authors.lastname: García-Buey
authors.forename: C
authors.initials: C
authors.lastname: Muñoz
authors.forename: N E
authors.initials: NE
authors.lastname: Quintana
authors.forename: J A
authors.initials: JA
authors.lastname: Moreno-Monteagudo
authors.forename: M J
authors.initials: MJ
authors.lastname: Borque
authors.forename: M J
authors.initials: MJ
authors.lastname: Fernández
authors.forename: F R
authors.initials: FR
authors.lastname: Salvanés
authors.forename: J
authors.initials: J
authors.lastname: Medina
authors.forename: R
authors.initials: R
authors.lastname: Moreno-Otero
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D004359:Drug Therapy, Combination; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008137:Longitudinal Studies; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D018417:Th1 Cells / Q000276:immunology; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a