The Association between the Changes in Serum Proteome and Sustained Virological Response in Chronic Hepatitis C Patients Treated with Pegylated Interferon Plus Ribavirin

Hepatitis C virus (HCV) infection is the leading cause of parenteral non-A, non-B viral hepatitis worldwide. Most of infected patients progress to chronic hepatitis, which may lead to liver cirrhosis and eventually development of hepatocellular carcinoma. The current therapy is interferon or pegylated interferon (PegIFN) in combination with ribavirin, which has yielded a sustained virological response (SVR) rate of 40–60% in patients with genotype 1 HCV infection, the prevalent genotype in Japan, Taiwan, Southern and Eastern Europe, and of around 80% in those infected with HCV genotypes 2 and 3. Though remarkable progress has been made in its effectiveness, the therapy is expensive and often associated with side effects that may lead to discontinuation. Therefore, it would be useful if one could predict ahead of time which patients are infected with IFN-sensitive HCV and which harbor resistant isolates. Many predictive parameters for IFN response have been reported including age, pretreatment viral load, HCV RNA at week 4 and 12, fibrosis stage, and HCV genotype, mutations in the NS5A region of HCV Type 1b and host genetic factors. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI--TOF/MS) is a proteomic technique that enables the global profiling of proteins. The recent development of proteomic array technology, including protein profiling with MALDI-TOF MS, provides a potentially powerful tool in the study of differential protein expression and post-translational modifications due to physiological conditions such as development, apoptosis, drug treatment and disease. The application of proteomics has led to the discovery of new biomarkers in patients with pancreatic, ovarian, prostate and liver malignancies. To date, only few studies investigated the association between serum proteome profiles and treatment response in chronic HCV patients. In this study, we aim to investigate the association between the changes in the serum proteome and sustained virological response (SVR) in chronic HCV patients treated with PEG-IFN plus ribavirin. In addition, we further identify protein peaks of potential interest. A total of 100 patients received or is receiving PegIFN α-2a or Peg IFN α-2b plus ribavirin for 6 or 12 months in our hospital will be included. Serums of patients will be used for MALDI analysis before starting treatment, at the end of treatment and at the end of the follow-up. At the end, we expect that serum proteome profiles variations differed according to the response to treatment might enable us to predict the RVR and SVR of antiviral therapy before and during treatment. Further identify protein peaks of potential interest by using MALDI-TOF/TOF. This technique might be useful for characterizing molecular species associated with these peaks to develop more simple serum tests. It would be very useful to develop simple serum tests for these identified biomarkers to predict and monitor treatment response in chronic hepatitis C patients.

Project ID:PC9609-3963
External Project ID:NSC96-2628-B182-020-MY2