Natural history of chronic hepatitis B virus infection in adults with emphasis on the occurrence of cirrhosis and hepatocellular carcinoma

The natural course of perinatally acquired hepatitis B virus (HBV) infectio n has three phases. In the first 'immune tolerance phase', patients are HBe Ag positive and have high serum levels of HBV DNA, but have no symptoms, no rmal ALT levels and minimal histological activity. The second 'immune clear ance phase' usually occurs between 15 and 35 years of age, during which HBV replication declines, accompanied by increased serum ALT levels and inflam matory activity in the liver; HBeAg to anti-HBe seroconversion is then obse rved, frequently preceded by a flare of the ALT level. The average rate of spontaneous HBeAg seroconversion is 10% per year. Tn the third 'low-replica tive phase', serum HBsAg persists, but HBeAg is no longer detectable and HB V DNA can only be detected by PCR assay. During this phase, patients are us ually asymptomatic and liver disease is inactive; some patients, however, m ay progress to cirrhosis and hepatocellular carcinoma (HCC). The ultimate o utcome of chronic HBV infection appears to depend on the duration and sever ity of liver injury during the immune clearance phase. About 2.1% of patien ts with chronic type B hepatitis develop cirrhosis each year. Patients who have a severe acute exacerbation complicated by subacute hepatic failure or who have recurrent episodes of acute exacerbations with bridging hepatic n ecrosis are more likely to develop cirrhosis. A significant proportion of t hose with HBsAg eventually develop HCC; they have a 100-fold increased risk of UCC relative to those without. The development of HCC, however, is clos ely related to the severity of the underlying liver disease. The annual inc idence of HCC is only 0.1% in asymptomatic HBsAg individual, 1% in patients with chronic hepatitis B, but increases to 3-10% in patients with cirrhosi s. Some anti-HBe-positive patients continue to have active liver disease an d they should be tested for HBV DNA by hybridization assay to determine whe ther the disease results from replicative precore mutant HBV infection or o ther causes of liver disease, such as superinfection with HCV and HDV. A su bstantial number of apparently healthy HBV-infected individuals are first r ecognized when they present with episodes of acute hepatitis. About 30% of these cases could be attributed to other hepatotropic virus superinfection. Acute viral hepatitis in patients with concurrent HBV infection is associa ted with an increased risk of fulminant hepatic failure. Finally, HBsAg dis appears from serum in about 1% of patients each year. HCV superinfection ca n enhance the termination of HBsAg positivity. HCV, however, replaces HBV a s the dominant cause of chronic viral hepatitis. The outcome of HBV-infecte d persons with 'spontaneous' seroclearance of HBsAg is usually favourable, though progress to cirrhosis and HCC is still possible. (C) 2000 Blackwell Science Asia Pry Ltd.