The Natural History of Chronic HBV Infection and Geographical Differences

Although chronic HBV infection is a global health issue, there are geographical differences in the mode of transmission, prevalence and HBV genotype distribution. Chronic HBV infection is a dynamic state of interactions between HBV, hepatocytes and immune cells of the host. Accordingly, the natural history of chronic HBV infection typically starts with an immune tolerant phase, followed by an immune clearance phase and finally an inactive phase. The duration of the immune tolerant phase is usually long in chronic HBV infection acquired perinatally or in early childhood, otherwise the duration is very short. During the inactive phase, spontaneous hepatitis B surface antigen (HBsAg) seroclearance might occur at an annual rate of 1–2%; however, HBV reactivation with hepatitis activity could occur over time in one-quarter to one-third of HBsAg-seropositive patients. This occurs more frequently in males and in patients infected with genotypes D, C and B. The effort of active HBV replication-triggered immune clearance is the driving force of liver injury and subsequent disease progression in patients with hepatitis B e antigen (HBeAg)-positive or HBeAg-negative hepatitis. Clinical studies have shown that chronic HBV infection in western countries is associated with a higher incidence of cirrhosis, but lower incidence of hepatocellular carcinoma, than in Asian countries. The geographical differences in age at the time of infection and predominant HBV genotype could account for the variance in the natural history of chronic HBV infection; however, some of these differences might actually result from comparisons between cohorts with different age, gender distribution or fibrosis stage.