Natural history of chronic hepatitis B virus infection.

In chronic hepatitis B virus (HBV) infection acquired during adulthood, which is the type mostly seen in the Caucasian population, there is biochemical and histologic regression after HBeAg seroconversion, and the risk of death from hepatitis B-related causes is low. In chronic HBV infection acquired during birth or early childhood, which is the type most commonly seen in the Asian population, there is a prolonged phase of immunotolerance. The immune clearance phase is characterized by multiple acute exacerbations preceeded by elevations in serum HBV DNA levels, HBeAg concentration and HBeAg/anti-HBe immune complexes. Of these patients, 2.4% may develop hepatic decompensation during the stage of HBeAg seroconversion. The development of cirrhosis occurs more frequently in patients with episodes of decompensation and with repeated severe acute exacerbations. However progression to cirrhosis can be relatively silent and can occur even in children. After HBeAg seroconversion, precore and core promotor mutations occur frequently in the Asian population. However, there is little correlation between the occurrence of these mutations and alanine aminotransferase elevation in patients who are positive for anti-HBe. Although cirrhosis develops during the process of HBeAg seroconversion, 68% of the complications of cirrhosis and of hepatocellular carcinoma occur after HBeAg seroconversion. These complications may still occur even after HBsAg seroclearance.