Abstract
Recent development of proteomic array technology, including protein profiling coupling ProteinChip array with surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF/MS), provides a potentially powerful tool for discovery of new biomarkers by comparison of its profiles according to patient phenotypes. We used this approach to identify the host factors associated with treatment response in patients with chronic hepatitis C (CHC) receiving a 48-wk course of pegylated interferon (PEG-IFN) alpha 2b plus ribavirin (RBV). Protein profiles of pretreatment serum samples from 32 patients with genotype 1b and high viral load were conducted by SELDI-TOF/MS by using the three different ProteinChip arrays (CM10, Q10, IMAC30). Proteins showed significantly different peak intensities between sustained virological responders (SVRs), and non-SVRs were identified by chromatography, SDS-PAGE, TOF/MS and tandem mass spectrometry (MS/MS) assay. Eleven peak intensities were significantly different between SVRs and non-SVRs. The three SVR-increased peaks could be identified as two apolipoprotein (Apo) fragments and albumin and, among the eight non-SVR-increased proteins, four peaks identified as two iron-related and two fibrogenesis-related protein fragments, respectively. Multivariate analysis showed that the serum ferritin and three peak intensity values (Apo A1, hemopexin and transferrin) were independent variables associated with SVRs, and the area under the receiver operating characteristic (ROC) curves for SVR prediction by using the Apo A1/hemopexin and hemopexin/transferrin were 0.964 and 0.936. In conclusion, pretreatment serum protein profiling by SELDI-TOF/MS is variable for identification of response-related host factors, which are useful for treatment efficacy prediction in CHC receiving PEG-IFN plus RBV. Our data also may help us understand the mechanism for treatment resistance and development of more effective antiviral therapy targeted toward the modulation of lipogenesis or iron homeostasis in CHC patients.
Highlights
Chronic hepatitis C (CHC) is among the leading causes of chronic liver disease worldwide, which afflicts approximately 170 million people [1]
Physicians have found that 20% of patients are nonvirological responders (NVRs; those whose hepatitis C virus (HCV) RNA does not become negative during 48 weeks of combination therapy)
Ten patients were included in the sustained virological responders (SVRs) group, 12 in the transient responder (TR) group, and the remaining 10 in the NVR group
Summary
Chronic hepatitis C (CHC) is among the leading causes of chronic liver disease worldwide, which afflicts approximately 170 million people [1]. The severity of disease varies from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma [2]. Combination therapy with pegylated interferon (PEG-IFN) alpha and ribavirin (RBV) is established as the most effective treatment for chronic hepatitis C virus (HCV) infection with genotype 1b, the sustained virological response (SVR) rate in these patients is still around 50% [3,4]. Physicians have found that 20% of patients are nonvirological responders (NVRs; those whose HCV RNA does not become negative during 48 weeks of combination therapy). Diction of NVR status is of clinical importance because these patients have no chance of achieving a sustained virological response even after prolonged combination therapy [5]. Considering side effects and treatment cost, prediction of treatment response before therapy with more reliable markers is mandatory
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