The natural history of chronic hepatitis B (CHB) phases comprise (1) HBe-Ag+ phase that includes immune tolerant phase (no hepatitis), and immune active, or immune clearance phase (active hepatitis phase), and (2) anti-HBe+/HBe-Ag– phase including inactive carrier (minimum or no hepatitis) and reactivation (HBe-Ag– active hepatitis) (Figure 1). Here, HBE1 is linked to chronic hepatitis B virus infection.