ABSTRACT

Hepatitis in humans has been described throughout history, but it was not until the twentieth century that distinct forms of the disease were characterized and ascribed to specic infectious agents. Studies involving humans, nonhuman primates (NHPs), and retrospective analyses of outbreaks and cases from the 1940s to 1960s revealed distinct forms of infectious hepatitis. One form of the disease was transmitted by the fecal-oral route with a relatively short incubation period, and a second form of the disease was transmitted parenterally. These diseases were later dened as hepatitis A and B, respectively. In the early 1970s, virus-like particles in the stools from human patients with hepatitis A were observed by immune electron microscopy (IEM) and presumptively called hepatitis A virus (HAV). In the late 1970s, a major development occurred with the demonstration that HAV

could be propagated in cultured cells following serial passage in marmosets. Molecular cloning and complete sequencing of HAV’s genome in the 1980s were followed by the licensure of hepatitis A vaccines in the United States in 1995, where the number of cases of hepatitis A have declined dramatically in recent years due to childhood vaccinations.