There is urgent need for novel immunotherapeutic strategies which, combined with current anti-viral therapy, may facilitate viral control and remove the need for long-term suppressive therapy in patients who have chronic hepatitis B virus (HBV) infection. To achieve this, it is critical to better understand mechanisms of innate and adaptive immune dysfunction and pathways of liver pathology. Here, we summarise recent advances pertaining to early immune events during acute HBV infection in an unusual cohort of patients sampled in the pre-clinical phase, and describe mechanisms of CD8 T cell attrition that apply to patients with chronic HBV infection. Furthermore, we describe a novel pathway of hepatocyte death mediated by innate natural killer (NK) cells. These pathways together provide novel pathogenic mechanisms for impaired viral control and liver damage during chronic HBV infection.
Copyright 2010 S. Karger AG, Basel.