Transfusion-associated hepatitis not due to viral hepatitis type A or B. 1975.
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Biomedical subjects
Publications and source records attributed to S M Feinstone.
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Progress in research on hepatitis type A has begun to accelerate because of the recent discovery of an antigen associated specifically with hepatitis type A infection and the development of tests for antibody to the antigen. Hepatitis A antigen is associated with 27 nm virus-like particles found in the liver and stool of animals experimentally infected with hepatitis type A and in the stool of humans experimentally or naturally infected with the virus. The density of the particulate antigen when isolated from the liver is 1.34, but antigen particles with densities ranging from 1.32 to 1.40 have been detected in stool. However, antigens from the liver and from the stool appear to be antigenically related. Using immune electron microscopy as a serologic tool for detecting antibody to hepatitis A antigen, we detected antibody in convalescent sera from 100 per cent of patients experimentally or naturally infected with hepatitis type A. In contrast, patients with hepatitis type B or non-B hepatitis not epidemiologically compatible with a diagnosis of hepatitis type A did not have a serologic response to hepatitis A antigen. Antibody was found in approximately 50 per cent of normal individuals tested; the frequency was directly related to age. By the use of immune electron microscopy for the detection of hepatitis A antigen and antibody, the temporal relationship of antigen, antibody and liver damage was determined in experimentally infected humans and chimpanzees. On the basis of serologic comparisons, hepatitis type A does not appear to be related to experimental hepatitis caused by the GB agent of Deinhardt, nor is the hepatitis A antigen serologically related to the fecal antigen of Cross.
Using the technique of immune electron microscopy we have conducted hepatitis A infectivity studies in marmoset monkeys and chimpanzees. Marmosets inoculated with human serum containing the MS-1 strain of hepatitis A virus have developed hepatitis and seroconverted to 27 nm virus-like particles isolated from stools of humans in the early acute stages of hepatitis. Similar results have been observed through several marmoset subpassages, and the virus-like particles have been recovered from the liver of animals in the acute phase of hepatitis. Chimpanzees inoculated with stool filtrates containing the virus-like particles develop hepatitis with concomitant excretion of the particles in early acute phase stools and subsequent development of serum antibody to the particles. These studies provide evidence that the above particles constitute the virus of hepatitis A of the MS-1 prototype.
Sera from individuals in an outbreak of viral hepatitis in a multifamily household, probably spread by contaminated food, were studied for antibodies to hepatitis A virus (anti-HAV), and selected acute phase sera were inoculated into marmosets. Significant rises in anti-HAV titers between acute and convalescent sera occurred in all of 15 individuals in the outbreak who experienced serum enzyme elevations and in one of 14 individuals whose serum enzyme levels remained normal. The remaining 13 individuals in the latter group had antibody levels in both early and late sera compatible with residual immunity from prior HAV infections and correlating with resistance to reinfection. Groups of marmosets were infected with acute phase sera from two of the cases; in both instances the inoculated sera contained substantial levels of anti-HAV. The marmosets developed specific anti-HAV seroconversions as well as enzyme elevations.
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