Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University, College of Medicine, Kaohsiung, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
Whether serum proteome changes can predict treatment response in chronic hepatitis C remains unclear. We investigated the association between serum proteome changes and virological responses in chronic hepatitis C virus genotype 1b (HCV-1b) patients treated with pegylated interferon (PegIFN) plus ribavirin (RBV).
MATERIALS AND METHODS:
One hundred and thirty-six HCV-1b patients who had completed a course of PegIFN plus RBV for 24 weeks, had a 24-week follow-up, and had pretreatment serum available were enrolled. These patients were divided into training and validation groups. We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) for peptide profiling and ClinPro Tools version 2.0 bioinformatics software for data analysis.
Seventy-four patients (54%) had a sustained virological response (SVR), whereas 62 did not. We identified three protein peaks in pretreatment sera where the expression levels significantly differed between SVR and non-SVR (p < 0.05). Using the class prediction tool composed of the three protein peaks, we were able to correctly predict SVR in 95% of validation group patients with sensitivity = 95%, specificity = 56.3%, positive predictive value = 73.1%, and negative predictive value = 90%. We also identified a set of 20 protein peaks where the expression levels significantly differed in pretreatment sera between patients with nonresponse (NR) and virological response (SVR plus relapse; p < 0.05). Using the class prediction tool composed of these 20 protein peaks, we were able to correctly predict virological NR in 82% of validation group patients with sensitivity = 100%, specificity = 82%, positive predictive value = 92.6%, and negative predictive value = 100%.
Pretreatment serum proteome allows prediction of SVR and NR to PegIFN plus RBV treatment in HCV-1b patients.