Involvement of dendritic cell frequency and function in virological relapse in pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C patients.
A combination of pegylated interferon alpha (PEG-IFNalpha) and ribavirin has been used widely. Enhancement of immune response against hepatitis C virus (HCV) is known to be involved in the efficacy of the combination therapy. The aim of the study was to elucidate whether the frequency or function of immunocompetent blood cells is related to the outcome of the therapy. Twenty-five chronic hepatitis C patients with high viral load of HCV genotype 1 who underwent 48 weeks of PEG-IFNalpha2b and ribavirin therapy were examined. During the treatment, frequencies of dendritic cell subsets, helper T cell subsets, and NK cells were phenotypically determined. In some patients, the ability of dendritic cells to stimulate allogeneic CD4(+)T cells was examined at the end and after the therapy. Among the 25 patients, 11 showed a sustained virological response, 11 a transient response, and 3 no response. In comparison with sustained virological responders, non-sustained virological responders showed impaired dendritic cell function at the end and after the treatment. The transient responders showed a decline of plasmacytoid dendritic cell frequency from Weeks 1-12 and impaired dendritic cell function as well. Even in patients who attained negative serum HCV RNA at Week 12, the transient responders showed a significant decrease of plasmacytoid dendritic cell frequency and impaired dendritic cell function. In conclusion, in PEG-IFNalpha and ribavirin combination therapy for chronic hepatitis C patients, the early-phase plasmacytoid dendritic cell frequency and/or end-of-treatment dendritic cell function are related to the virological outcome of the therapy.
Itose
Ichiyo
I
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan.
Kanto
Tatsuya
T
Inoue
Michiyo
M
Miyazaki
Masanori
M
Miyatake
Hideki
H
Sakakibara
Mitsuru
M
Yakushijin
Takayuki
T
Oze
Tsugiko
T
Hiramatsu
Naoki
N
Takehara
Tetsuo
T
Kasahara
Akinori
A
Katayama
Kazuhiro
K
Kato
Michio
M
Hayashi
Norio
N
D000998:Antiviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002452:Cell Count; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D004337:Drug Carriers / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome
D000998:Antiviral Agents; D004337:Drug Carriers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a