The natural history of hepatitis B virus infection

Abstract

Hepatitis B virus (HBV) is responsible for two thirds of cases of acute clinical hepatitis in Greece, while 3% of the population are chronic HBV carriers. Acute hepatitis B is usually a subclinical or symptomless infection and in only 20 - 30% of cases present as clinical or symptomatic hepatitis although it may present as fulminant or subacute hepatitis both of which are associated with a poor survival rate. Acute hepatitis B is usually a self-limited infection which leaves long-life immunity. However, some patients progress to chronicity and the risk for chronicity depends mainly on the patient's age and immunocompetence. Positive serum HBeAg for more than three months is a strong predictor for progression to chronicity. The first phase of chronic HBV infection (immunotolerance or replicative phase) is characterised by immunologic inactivity, high viral replication and absence of severe histologic lesions. The immune system activation indicates the start of the clearance or seroconversion phase, which may be complete (clearance of HBeAg) or incomplete, the form characterised by variable duration and associated with the most severe lesions in the hepatic parenchyma. The integration phase follows complete seroconversion and is a long phase with the virus remaining in the hepatocyte DNA and with HBV-DNA undetectable by the usual assays. The chronic HBsAg or HBV carriers belong to this phase. Precore mutations enable HBV to replicate without HBeAg production and to reactivate even after integration (chronic hepatitis due to precore HBV mutant). Reactivation of HBV is observed in one quarter of chronic HBsAg carriers and thus the need for regular follow-up is obvious. The etiologic relation of chronic HBV infection with hepatocellular cancer constitutes another important risk for such patients. The risk for cancer is higher in cases with cirrhosis and with a longer duration of infection, but cancer has been observed even in chronic HBV carriers and in serologically immune individuals.