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

Aim 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 / A ge model). The sensitivity and specificity of the C3f‐dR/PLT model were 59% and 88%, and those of the 107P/Hb/BMI / A ge model were 70% and 92%, respectively. The C3f‐dR/PLT model showed high AUROC (0.82), similar to that of interleukin‐28 B rs8099917 genotype analysis (0.86) in the 45 tested patients. Prediction by the combination of the C3f‐dR/PLT model, the 107P/Hb/BMI / A ge model and the rs8099917 genotype analysis was accurate in 44 out of the 45 patients ( AUROC , 0.95). Conclusion 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.