Immune Regulation and Costimulation in Natural History of Chronic Hepatitis B

Hepatitis B, a significant cause of cirrhosis and hepatocellular carcinoma worldwide, affects an estimated 800,000 to 1.4 million people in the United States. While progress has been made in the prevention, diagnosis, and treatment of chronic hepatitis B, challenges remain in identifying persons affected by the virus and in determining recommendations for management and treatment. The Hepatitis B Research Network (HBRN) was a multicenter network to investigate the etiology and progression of the disease, and to test the safety and efficacy of current treatment approaches. Hepatitis B virus (HBV) is largely a non-cytopathic virus. Therefore, liver disease pathogenesis and viral clearance in HBV infection is believed to be immune-mediated. At the same time, HBV persists with impaired antiviral immune effector responses that are potentially regulated by multiple immune pathways, including the CD28 costimulatory receptors and immune regulatory T cells. The Immune Regulation and Costimulation in Natural History of Chronic Hepatitis B (HBRN Immunology Cohort) study aimed to assess whether the balance between immune regulatory and effector responses in HBV-infected individuals defines the level of viremia, liver inflammation, and treatment outcomes.