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.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Osaka Kaisei Hospital, Yodogawa-Ku, Osaka City, Osaka, Japan. y-kishida@muse.ocn.ne.jp
Yutaka
Y
Kishida
Yoshimichi
Y
Haruna
Masahumi
M
Naitoh
Kazuhiro
K
Katayama
Toru
T
Kashiwagi
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