n the past 10 years, remarkable strides have been made in the understanding of the natural history and pathogenesis of hepatitis B virus (HBV) infection. In this article we will review these advances, with particular reference to the implications for antiviral therapy.
Clinical and epidemiologic studies began to differentiate among various types of acute hepatitis in the decades after World War II. The groundbreaking studies of Krugman and colleagues in 1967 firmly established the existence of at least two types of hepatitis, 1 one of which (then called serum hepatitis, and now called hepatitis B) was parenterally transmitted. Links to the virus responsible for this form of hepatitis were derived by serologic studies conducted independently by Prince and colleagues 2-4 and by Blumberg and colleagues. 5 Blumberg and colleagues, searching for serum protein polymorphisms linked to diseases, identified an antigen (termed Au) in serum from patients with leukemia, leprosy, and hepatitis, though the relationship of this antigen to hepatitis was initially unclear. By systematically studying patients with transfusionassociated hepatitis, Prince and coworkers independently identified an antigen, termed SH, that appeared in the blood of these patients during the incubation period of the disease, and further work established that Au and SH were identical. 6,7 The antigen represented the hepatitis B surface antigen (HBsAg). 8,9 These seminal studies made possible the serologic diagnosis of hepatitis B and opened up the field to rigorous epidemiologic and virologic investigation.