Hepatitis A virus infection: pathogenesis and serodiagnosis of acute disease

The early development of immune electron microscopic (IEM) methods for the detection of HAV in acute-phase stool suspensions and antibody to HAV (anti-HAV) in serum made it possible to serologically identify cases of hepatitis A using paired acute and convalescent phase sera. Introduction of less cumbersome and time-consuming serologic test methods, including complement fixation (CF) and immune adherence hemagglutination (IAHA), made it feasible to rapidly assay larger numbers of specimens for HAV or anti-HAV. Subsequent development of sensitive immunofluorescence (IF) assays, solid-phase radioimmunoassays (RIA), and enzyme immunoassays (EIA) for HAV and anti-HAV heralded intensive laboratory studies of the biophysical and biochemical properties of the virus as well as efforts to define the pathogenesis and clinical course of disease. Results of the latter studies showed that the bulk of HAV was usually excreted in stool before the onset of clinical symptoms. Other serologic studies demonstrated that all acutely ill patients had circulating anti-HAV IgM, while all convalescent patients were positive for anti-HAV IgG. The development of sensitive serologic tests (RIA and EIA) that could differentiate between anti-HAV IgM and IgG made it possible to serodiagnose an acute case of hepatitis A using a single-phase serum specimen.