title: Association of serum cytokine levels with treatment response to pegylated interferon and ribavirin therapy in genotype 1 chronic hepatitis C patients.
abstract: BACKGROUND
  We sought to clarify the associations among serum cytokines, amino acid substitutions in the interferon sensitivity-determining region (ISDR) and core region, and treatment outcome of pegylated interferon and ribavirin therapy in genotype 1 hepatitis C virus (HCV)-infected patients.
  
  
  METHODS
  We quantified a total of 8 serum cytokines before, during, and after treatment in 79 genotype 1 chronic HCV patients. Viral ISDR and core region variants were determined by direct sequencing.
  
  
  RESULTS
  High levels of interleukin (IL)-12 and IL-18 and more than 2 mutations in the ISDR were associated with a sustained virological response (SVR). Conversely, high baseline IL-10 levels and glutamine at amino acid 70 of the HCV core protein (Gln70) were significantly associated with a nonresponse to treatment, and patients with Gln70 had significantly higher IL-10 levels. In multivariate analysis, low IL-10, high IL-12, and high IL-18 levels were independently associated with an SVR. These 3 cytokine levels were decreased from baseline levels 4 weeks into treatment and remained low in patients with an SVR.
  
  
  CONCLUSIONS
  Serum IL-10, IL-12, and IL-18 levels are predictive of the response to HCV treatment with pegylated interferon and ribavirin and are associated with amino acid substitutions in the ISDR and core region.
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Yoneda
authors.forename: Takeji
authors.initials: T
authors.lastname: Umemura
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Katsuyama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kamijo
authors.forename: Satoru
authors.initials: S
authors.lastname: Joshita
authors.forename: Michiharu
authors.initials: M
authors.lastname: Komatsu
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ichijo
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Kaname
authors.initials: K
authors.lastname: Yoshizawa
authors.forename: Masao
authors.initials: M
authors.lastname: Ota
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
mesh_terms: D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers; D016207:Cytokines / Q000097:blood*; D018936:Hepatitis C Antigens / Q000097:blood; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D014758:Viral Core Proteins / Q000097:blood
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D016207:Cytokines; D018936:Hepatitis C Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014758:Viral Core Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b