title: Dynamics of regulatory T cells and plasmacytoid dendritic cells as immune markers for virological response in pegylated interferon-α and ribavirin therapy for chronic hepatitis C patients.
abstract: BACKGROUND
  For the treatment of chronic hepatitis C, a combination of pegylated interferon-α (PEG-IFNα) and ribavirin has been widely used as a standard of care. Enhancement of immune response against hepatitis C virus (HCV) is known to be involved in the efficacy of the combination therapy. Our aim was to elucidate whether or not the frequency or function of blood cells is related to the outcome of the therapy.
  
  
  METHODS
  Sixty-seven chronic hepatitis C patients with high viral load of HCV genotype 1 infection who underwent 48 weeks of PEG-IFNα2b and ribavirin therapy were examined. During the treatment, frequencies of myeloid or plasmacytoid dendritic cells, Th1, Th2 cells, NK cells, and regulatory T cells were phenotypically determined.
  
  
  RESULTS
  Among the patients enrolled, 29 showed a sustained virological response (SVR), 18 a transient response (TR) and 17 no response (NR). The clinical and immunological markers were compared between the SVR and non-SVR patients, including TR and NR. Based on clinical, histological, immunological parameters, and cumulative dosage of PEG-IFNα2b and ribavirin, multivariate analyses revealed that higher platelet counts and higher regulatory T cell frequency at week 12 are indicative of SVR. Even in patients who attained complete early virological response at week 12, multivariate analyses disclosed that higher platelet counts and higher plasmacytoid dendritic cell frequency are indicative of SVR.
  
  
  CONCLUSIONS
  In PEG-IFNα and ribavirin combination therapy for chronic hepatitis C patients, the increments of regulatory T cells and plasmacytoid dendritic cell frequency are independently related to favorable virological response to the therapy.
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. kantot@gh.med.osaka-u.ac.jp
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kanto
authors.forename: Michiyo
authors.initials: M
authors.lastname: Inoue
authors.forename: Tsugiko
authors.initials: T
authors.lastname: Oze
authors.forename: Masanori
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sakakibara
authors.forename: Naruyasu
authors.initials: N
authors.lastname: Kakita
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Matsubara
authors.forename: Koyo
authors.initials: K
authors.lastname: Higashitani
authors.forename: Hideki
authors.initials: H
authors.lastname: Hagiwara
authors.forename: Sadaharu
authors.initials: S
authors.lastname: Iio
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Katayama
authors.forename: Eiji
authors.initials: E
authors.lastname: Mita
authors.forename: Akinori
authors.initials: A
authors.lastname: Kasahara
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiramatsu
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010976:Platelet Count; D012254:Ribavirin / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin