Ultrastructural alterations in serial liver biopsy specimens from chimpanzees experimentally infected with a human...

Four chimpanzees experimentally infected with an agent of human non-A, non-B hepatitis were studied to determine the sequence of ultrastructural alterations in hepatocytes during infection. Three of the four types of cytoplasmic alterations previously described in association with non-A, non-B hepatitis were observed in the hepatocytes. Sponge-like cytoplasmic inclusions (designated C-I) were detected at or near the time of peak serum aminotransferase elevations in two of the four chimpanzees. Undulating membranes (designated C-II) were observed in all four chimpanzees, at the time of the first elevation of serum aminotransferase levels. Cytoplasmic tubules (designated C-III) were first observed four, eight, and twelve weeks, respectively, after inoculation in three of the chimpanzees. Four weeks after the peak of serum aminotransferase elevations, cytoplasmic alterations could no longer be detected in hepatocytes of the four chimpanzees. Intranuclear inclusions consisting of 20-27 nm granules and vermicular particles were observed in hepatocytes from preinoculation liver biopsy specimens, as well as biopsies obtained during non-A, non-B hepatitis. The number of these particles was greatest near the time of peak elevation of serum aminotransferase levels, however. Tubulo-crystalline inclusions were noted as well in the endothelial cells from both preinoculated and infected chimpanzees. Cytoplasmic alterations in hepatocytes of chimpanzees experimentally infected with an agent of non-A, non-B hepatitis appear characteristic of infection with this agent. In contrast, intranuclear particles were not specifically related to the non-A, non-B hepatitis infection.