The focus of our lab's research centers around the role of B lymphocytes in the cirrhotic progression of nonalcoholic steatohepatitis (NASH). NAFLD represents a progressive spectrum of liver disease beginning with simple steatosis and leading to NASH, fibrosis and ultimately cirrhosis. NAFLD is the most common liver abnormality in the world. NASH is characterized by hepatic infiltration of inflammatory cells and subsequent hepatocellular injury. Determining the role that specific cells play is vitally important in developing effective diagnostic and treatment tools. Our preliminary data in a murine model of NASH suggests that a subset of B lymphocytes is recruited to the liver during NASH progression and is responsible for initiating fibrosis. Our lab has demonstrated that B lymphocytes are critical to the development of NASH fibrosis. Validation of this hypothesis in the human experience will be accomplished with two specific aims that will determine the mechanism of B lymphocyte recruitment during NASH progression and elucidation of the pro-fibrotic role of B lymphocytes in the liver. These studies will provide novel new information about the pathogenesis of NASH that may be applicable to other fibrotic liver diseases. In addition this may lead to noninvasive tests to diagnosis liver fibrosis and patients that will proceed to cirrhosis.