Hepatitis C virus (HCV) mediated end stage liver disease, including hepatocellular carcinoma (HCC), is a growing problem among African Americans (AAs). The central goal of this project is to investigate the racial disparity of HCV mediated liver cancer. HCV infection mediated death rate among AA patients is about 2- fold higher than CA. Very little information is available about the underlying mechanisms of liver disease progression among chronically HCV infected ethnic groups. Our research proposal will examine this previously unexplored area of HCV mediated end stage liver disease among AA. microRNAs (miRNAs) play critical roles in multi-step cell growth regulatory processes, and the relationship between chronic HCV infection and miRNA expression is of considerable interest in understanding virus mediated disease progression. Our preliminary data indicated a group of microRNAs modulated in chronically HCV infected AA sera as compared to that of CA. We hypothesize that these circulatory miRNAs can be potential predictive biomarker towards HCC development in HCV infected AA patients, and are involved deregulating hepatocyte growth. Thus, identification of predictive biomarkers for HCC and the underlying molecular mechanisms for race disparity will have a great translational benefit. Our long term objectives are to translae these findings from the laboratory to the bedside identifying predictive biomarker, and developing therapeutic modalities for HCV mediated liver disease progression. Impact: The results from this R21 exploratory proposal will have a high impact by investigating the role of miRNAs as genetic factors for understating racial disparity. Our research will explain why African Americans have higher incidence of HCV mediated liver cancer as compared to Caucasians.