Grant: Project Grant

Chronic viral hepatitis, such as hepatitis C (HCV), remains the leading cause of liver disease-related death despite treatment advancements. This is partly because of ongoing immune system changes that continue to damage the liver, even after the virus is treated. Additionally, more people are being diagnosed with metabolic dysfunction-associated steatotic hepatitis (MASH), which often occurs alongside chronic viral hepatitis. Together, these conditions worsen liver damage and increase the risk of liver cancer. In this project, we aim to explore how the immune system, specifically a type of immune cell called CD8 T cells, is affected in people with chronic liver diseases like HCV and MASH. We have observed that these immune cells become dysfunctional in patients with advanced liver damage, which may contribute to the development of liver cancer and reduce the effectiveness of treatments. Our research will investigate how CD8 T cells malfunction in these conditions and whether certain biological pathways, such as those involved in cell energy use (glycolysis and oxidative phosphorylation) and signaling pathways (Hedgehog signaling), play a role in this dysfunction. Using both human liver samples and animal models, we will study how these pathways interact to affect the immune response in the liver. Ultimately, we hope to better understand how these immune cell changes contribute to liver cancer and how we can improve treatments that target this immune dysfunction. This research is significant for improving the understanding and treatment of chronic viral hepatitis, MASH, and liver cancer. By identifying the biological mechanisms behind immune system changes in liver disease, our findings could lead to more effective therapies for these conditions, benefiting patients worldwide.