Multiple cytokine profiling of the therapeutic responses to ribavirin and pegylated interferon-alpha2b using an "induction" approach with natural interferon-beta in difficult-to-treat chronic hepatitis C.
Cyclic and periodic IFN treatment (CPIT) consisting of induction treatment with nIFN-beta followed by maintenance treatment with IFN-alpha could prevent viral breakthrough and achieve rapid virological response (RVR) and early virological response (EVR) in chronic hepatitis C (CHC). The efficacy and immune response of RBV+PEG-IFN-alpha2b using induction approach with CPIT (novel combination treatment: NCT) in 7 CHC patients with genotype 1b and high viral load were evaluated. A biometric multiplex serum cytokine assay was utilized to characterize the immunomodulatory effect. RVR and EVR were 7/7 and 7/7, respectively. Viral titers dropped below detectable levels in five patients with sustained virological response (SVR) before the end of CPIT (early virological responder: EAVR), and two patients without SVR after the end of CPIT (late virological responder: LAVR). At baseline, in EAVR compared with the controls, IL-6 and IL-15, CXCL-8 and CXCL-10 levels were significantly higher (P < 0.05); IL-10 and IL-13 levels were significantly lower (P < 0.05); and the IL-12 level was lower. In LAVR, GM-CSF, CXCL-8 and CXCL-10, and CCL-4 levels were significantly higher (P < 0.05); and IL-10 and IL-12 were lower than the controls. In EAVR but not LAVR, the IL-12 increased and the CCXL-8 decreased significantly (P < 0.05). In conclusion, NCT-induced viral clearance leading to improvement in the innate immune response resulting in SVR in CHC with genotype 1b and high viral load.
Kishida
Yutaka
Y
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Osaka Kaisei Hospital, Yodogawa-Ku, Osaka City, Osaka, Japan. y-kishida@muse.ocn.ne.jp
Haruna
Yoshimichi
Y
Naitoh
Masahumi
M
Katayama
Kazuhiro
K
Kashiwagi
Toru
T
D000328:Adult; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000276:immunology*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D020869:Gene Expression Profiling; D016174:Hepacivirus / Q000276:immunology* / Q000472:pathogenicity; D018937:Hepatitis C Antibodies / Q000097:blood / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D016899:Interferon-beta / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D012698:Serologic Tests; D015533:Transcriptional Activation / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome; D019562:Viral Load; D014774:Virulence / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; D018937:Hepatitis C Antibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D016899:Interferon-beta; C100416:peginterferon alfa-2a