HBV is highly infectious; many chronic HBsAg carriers were infected in their family shortly after birth or in early childhood (5-7). Recent genome-wide association studies revealed antigen presenting molecules, Human leukocyte antigen-DP (HLA-DP) and HLA-DQ, are associated with persistence HBV infection (8-10). HBV is actively replicated in chronic carriers during the initial immune tolerance phase (11). Impaired innate and adaptive immune responses to HBV can be found during this stage (12-16). They are generally asymptomatic until the immune clearance phase developed. At this stage, innate immunity, HBV-specific and non-specific T cells and other immune cells may orchestra an immune response and hepatic necroinflammation to clear HBV (17-19). The immune clearance phase is critical to the outcome of chronic HBsAg carriers. Those patients with prolonged HBV replication and repeated hepatic inflammation will run into liver cirrhosis and /or hepatocellular carcinoma (HCC) (20-23). How to terminate HBV replication is an important issue in management of chronic HBsAg carriers.