Chronic hepatitis C virus (HCV) infection is a significant clinical problem throughout the world. The number of Americans infected with HCV is approximately 4 million. About 85% of people infected with HCV develop chronic infection and approximately 70% of patients develop histological evidence of chronic liver disease. Cirrhosis due to chronic HCV is now the leading indication for liver transplantation in the United States. The ultimate goal of the proposed research is to develop a simple, minimally invasive and clinically useful diagnostic that can be used to individualize therapy in patients with chronic HCV. Current combination therapy of peginterferon and ribavirin results in a ~50% sustained virological response (SVR) rate, thus about half of patients do not achieve a response with 48 weeks of therapy. Although viral load and genotype, race, and degree of fibrosis have been shown to be important predictors of response, identification of additional host immune and genetic factors involved in determining outcome of antiviral therapy is necessary. Additionally, treatment with interferon alpha and ribavirin can lead to significant toxicities. Early prediction of response could limit unpleasant side effects and reduce cost of treatment in the non-responder population. The specific aims of this research proposal are to: 1) demonstrate a characteristic pattern of gene expression in peripheral blood cells of patients with chronic HCV; 2) identify changes in gene expression in blood samples from chronic HCV patients that correlate with clinical response to peginterferon/ribavirin therapy. To meet these aims a gene expression panel will be analyzed by high precision quantitative PCR of whole blood samples from patients with chronic HCV collected before and during the course of treatment. This analysis will be compared initially to the early virological response (EVR) at week 12 of therapy and later to the SVR, 6 months after therapy completion. EVR, defined as a minimum 2-log decrease in viral load during the first 12 weeks of treatment, may be predictive of SVR.
Thesaurus Terms: combination chemotherapy, diagnosis design /evaluation, gene expression, hepatitis C, hepatitis C virus, interferon, microorganism disease chemotherapy, pharmacogenetics, ribavirin clinical research, human subject, polymerase chain reaction
