DETECTION OF HEPATITIS-E VIRUS GENOME AND GENE-PRODUCTS IN 2 PATIENTSWITH FULMINANT HEPATITIS-E

Non-isotopic in situ hybridization (digoxigenin-labeled probe directed towards hepatitis E virus ORF1) and immunohistochemistry (against hep atitis E virus ORF2 and ORF3) were applied to detect hepatitis E virus genome and gene product in the liver tissue of two patients with fulm inant hepatitis E seropositive for hepatitis E virus RNA, Both hepatit is E virus RNA and hepatitis E virus antigens were detected exclusivel y in the cytoplasm of hepatocytes and not detected in other cell types , In both patients, more than 50% of the hepatocytes were positive for both hepatitis E virus RNA and hepatitis E virus antigens, most of wh ich showed degenerative changes, This is consistent with the histologi cal appearance of marked loss of hepatocytes with acinar collapse, Int erestingly, denaturation of the RNA before in situ hybridization was f ound to enhance hepatitis E virus RNA detection, We conclude that: (1) hepatitis E virus RNA and hepatitis E virus antigens can be demonstra ted in the liver in hepatitis E virus-related fulminant hepatitic fail ure, (2) hepatitis E virus is hepatocyte-tropic within the liver, (3) cytoplasmic localization of hepatitis E virus RNA and hepatitis E viru s antigens is consistent with cytoplasmic replication, and (4) the pre sence of degenerative changes in hepatitis E virus positive cells, tog ether with the histological appearance of hepatocyte loss in the absen ce of significant inflammatory infiltrate, suggests that hepatitis E v irus-related fulminant hepatitic failure is mediated by a cytopathic m echanism.