1173 IDENTIFICATION AND CHARACTERIZATION OF PPI-383, A NEXT GENERATION HCV NS5B NON-NUCLEOSIDE INHIBITOR WITH POTENT ACTIVITY AGAINST ALL MAJOR HCV GENOTYPES

virological response (SVR). Of the host determinants, age, gender, race, insulin resistance, host immune responses and genetic predispositions might significantly correlate to the achievement of SVR. Several studies have shown that some specific MicroRNAs (miRNAs) sets are associated with the clinicopathological features of liver disease, such as cirrhosis, hepatitis B and C virus infection, hepatocellular carcinoma metastasis, recurrence, and prognosis. Recently, Disease-associated miRNA in peripheral blood mononuclear cells (PBMC) have been described for several diseases. Thus, PBMC-contained miRNAs have a great potential to serve as non-invasive markers. Objective: To find miRNAs associated with interferon-based therapy response. Methods: We used a two steps method to find miRNA associated with treatment response to standard-of-care with peginterferonribavirin for CHC patients. 1. Performing expression profile of 754 miRNAs in PBMC of 13 CHC patients before antiviral therapy by QPCR-based array; 2. Validating candidate miRNAs in an independent 47 CHC patients by QPCR. Results: Nine miRNAs with highest fold change were selected for validation. Two miRNAs were expressed lower significantly in nonSVR patients. After controlling the other potential factors, including IL28B genotype, the most powerful baseline predictor, miR-5xx remained significantly associated with SVR. Conclusions: PBMC-contained miRNAs have a great potential to serve as potential baseline markers for predicting SVR of CHC patients.