Natural history of chronic hepatitis B virus infection

The natural course of perinatally acquired chronic hepatitis B virus (HBV) infection typically has three chronological phases: (1) the immune-tolerant phase, (2) the immune clearance phase, and (3) the inactive or residual phase. However, no obvious initial immune-tolerant phase is evident in adult-acquired chronic infection. Hepatitis B e antigen (HBeAg) seroconversion is a hallmark and usually signals the transition from active to inactive HBV infection with alanine aminotransferase (ALT) normalization and resolution of hepatitis activity. After long sustained remission, spontaneous hepatitis B surface antigen (HBsAg) seroclearance may occur and confers excellent prognosis. On the other hand, HBV may reactivate and trigger immune-mediated liver injuries at an incidence of 2-3% per year, usually in the first 10 years after HBeAg seroconversion. High HBV DNA levels and disease activity are the factors of adverse clinical outcomes such as hepatic decompensation, cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality. Sustained reduction of HBV replication before the onset of cirrhosis confers a favorable outcome.