Grant: Operating Grant - Priority Announcement: Hepatitis C - biomedical/clinical

Hepatitis C virus (HCV) infection usually causes a life-long persistent infection in humans that can lead to irreversible liver damage and even cancer. End-stage liver disease caused by HCV infection is the main cause of liver transplantation and liver cancer in North America. There is no vaccine for HCV and the only available treatment is expensive, has many side effects and is effective only in half of the infected population. Our team is studying the immune response against hepatitis C virus infection and why only a small fraction of infected individuals are able to eliminate the virus without treatment. We know that the nature of the immune mediators (known as cytokines) causing inflammation of the liver during hepatitis C virus infection can influence the degree of liver damage. Such immune mediators are secreted by white blood cells known as CD4 T cells that infiltrate the liver. Interestingly, these same mediators can reduce the efficacy of the immune response against the virus and facilitate the development of chronic infection. In this proposal we plan to study the CD4 T cell subset of white blood cells and try to characterize the immune mediators that they produce. We will then test the other immune cell subsets that influence cytokine production by CD4 T cells. Finally, we will test the level of these mediators in the liver and test them individually to identify which ones are the major inducers of liver fibrosis. The goal of this project is to understand the immune mediators that can reduce liver inflammation in hepatitis C and hence delay liver disease/fibrosis progression which is a major cause of liver cancer. This will help in developing new treatments for hepatitis C and liver fibrosis.