Hepatitis B virus transgenic mice: Insights into the virus and the disease

The hepatitis B virus (HBV) is a noncytopathic, enveloped virus with a circular double-stranded DNA genome that causes acute and chronic necroinflammatory liver disease and hepatocellular carcinoma.'HBV infection acquired in adult life is often clinically inapparent, and most acutely infected adults recover completely from the disease and clear the virus.Rarely, however, the acute liver disease may be so severe that the patient dies of fulminant hepatitis.A small fraction, perhaps up to 5%, of acutely infected adults become persistently infected by the virus and develop chronic liver disease of varying severity.Neonatally transmitted HBV infection, however, is rarely cleared, and more than 90% of such children become chronically infected.Because HBV is commonly spread from infected mother to newborn infant in highly populated areas of Africa and Asia, several hundred million people throughout the world are persistently infected by HBV for most of their lives and suffer varying degrees of chronic liver disease, which greatly increases their risk of developing cirrhosis and hepatocellular carcinoma (HCC).Indeed, the risk of HCC is increased 100fold in patients with chronic hepatitis, and the lifetime risk of HCC in males infected at birth approaches 40%.2Accordingly, a large fraction of the world's population suffers from and dies of these late complications of HBV infection.It is generally thought that HBV is not directly cytopathic for the hepatocyte but that the associated liver diseases are caused by the immune response to viral antigens expressed by infected hepatocytes.HBV-in-