title: Serum peptides, represented by complement 3f des-arginine, are useful for prediction of the response to pegylated interferon-α plus ribavirin in patients with chronic hepatitis C.
abstract: OBJECTIVE
  Biomarkers predicting sustained virological response (SVR) to pegylated interferon-α plus ribavirin (PEG IFN-α/RBV) were investigated.
  
  
  METHODS
  Peptides in pretreatment sera from 107 patients with hepatitis C virus (HCV) genotype 1 were comprehensively analyzed by mass spectrometry. Ion intensity of the peptides was used to generate discriminant models between the responders who achieved SVR (R) and the non-responders (NR) to PEG IFN-α/RBV.
  
  
  RESULTS
  In total, 107 peptides were detected in a training set (n = 23). A discriminant model using a peptide, complement 3f des-arginine (C3f-dR), showed sensitivity of 35% and specificity of 94% for SVR prediction in a testing set (n = 68). In all the R and NR (n = 96), an area under the receiver-operator curve (AUROC) of 0.64 in the C3f-dR model was increased to 0.78 by addition of platelet (PLT) counts (C3f-dR/PLT model). Another model using the 107 peptides (AUROC, 0.77) also showed higher AUROC (0.79) by addition of hemoglobin (Hb), body mass index (BMI) and age (107P/Hb/BMI/Age model). The sensitivity and specificity of the C3f-dR/PLT model were 59% and 88%, and those of the 107P/Hb/BMI/Age model were 70% and 92%, respectively. The C3f-dR/PLT model showed high AUROC (0.82), similar to that of interleukin-28B rs8099917 genotype analysis (0.86) in the 45 tested patients. Prediction by the combination of the C3f-dR/PLT model, the 107P/Hb/BMI/Age model and the rs8099917 genotype analysis was accurate in 44 out of the 45 patients (AUROC, 0.95).
  
  
  CONCLUSIONS
  Serum peptides, especially C3f-dR, would be useful predictors for SVR to PEG IFN-α/RBV. The complements may be involved in the HCV elimination.
authors.affiliation: Clinical Proteomics and Molecular Medicine, St Marianna University Graduate School of Medicine, Japan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, St Marianna University School of Medicine, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Noguchi
authors.forename: Manae S
authors.initials: MS
authors.lastname: Kurokawa
authors.forename: Chiaki
authors.initials: C
authors.lastname: Okuse
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Kouhei
authors.initials: K
authors.lastname: Nagai
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sato
authors.forename: Mitsumi
authors.initials: M
authors.lastname: Arito
authors.forename: Naoya
authors.initials: N
authors.lastname: Suematsu
authors.forename: Kazuki
authors.initials: K
authors.lastname: Okamoto
authors.forename: Michihiro
authors.initials: M
authors.lastname: Suzuki
authors.forename: Fumio
authors.initials: F
authors.lastname: Itoh
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kato