EXPERIMENTAL HEPATITIS-E - PATHOGENESIS IN CYNOMOLGUS MACAQUES (MACACA-FASCICULARIS)

The pathogenesis of experimental hepatitis E has not been thoroughly i nvestigated. The purpose of this study was to more accurately document the events in this disease. Cynomolgus macaques were inoculated intra venously with bile or feces containing hepatitis E virus (HEV). Serum, bile, and liver specimens were evaluated with light microscopy, immun e electron microscopy, immunofluorescence microscopy, EIA, and polymer ase chain reaction. In the third week, there were histopathologic chan ges and HEV antigen (HEVAg) in liver, HEV in bile, and alanine aminotr ansferase (ALT) elevations. Widespread pathologic changes were detecte d during the fourth week and antibody to HEV (anti-HEV) and peak ALT v alues in the fifth or sixth week. By the sixth week, HEVAg had disappe ared but pathologic changes persisted. This study supports the concept that experimental hepatitis E has an initial phase in which hepatic H EV replication is accompanied by the onset of hepatitis and a later ph ase in which the appearance of anti-HEV is accompanied by progression of the hepatitis.