New aspects on the natural history of chronic hepatitis B infection: implication for therapy

The incidence and sequelae of chronic hepatitis B (HBV) infection appear to have been overestimated previously, especially in areas outside Asia where neonatal infection predominates. A high rate of spontaneous HBeAg seroconversion is found in children as well as adults, and 40 to 50 y of replicative infection seems to be the most important risk factor for cirrhosis and hepatocellular carcinoma necessitating a cautious attitude towards antiviral treatment. Of concern, however, HBeAg seroconversion, which usually predicts a good outcome, is not always an irreversible event. Low grade replication of HBV may continue in anti-HBe positive individuals and shift in HBe status does occur in up to 10% of viral carriers with evidence of an increased risk of complications. Viral replication (HBV DNA positivity) is also found in HBeAg negative mutant infection and is an important parameter to note. To date, the data do not suggest any different prognosis for patients with this kind of infection. Also the various viral genotypes might have different prognoses partly due to the association with precore mutations, but the present knowledge does not allow different therapeutic management as in the case of hepatitis C. Treatment is available with a number of safe antiviral agents. However, all of them are mainly suppressive with low cure rates after 1 y. Initiation of therapy should therefore mainly be considered in symptomatic chronic infection and in cases with high risk of complications i.e. patients with ongoing viral replication and age above 40 y or bridging necroses verified by liver biopsy.