Liver involvement in epidemic haemorrhagic fever: in situ hybridization, immunohistochemical and pathological studies

In the present study, liver biopsy specimens from 37 patients with epidemic haemorrhagic fever (EHF) were investigated by using light and electron microscopy, immunohistochemistry for the EHF virus envelope protein G2 and in situ hybridization (ISH) for EHF viral RNA. Immunostaining and in situ hybridization were both positive, and a few of the aetiological agents, the EHF virus (EHFV) particles, were found individually within the dilated Golgi cisternae and vesicles, and the dilated rough endoplasmic reticulum of the hepatocyte. The pathological alterations of the liver cells infected with EHFV were: hepatocellular degeneration, cytoplasmic vacuolation, and spotty necrosis; moreover, zonal necrosis was present and adjacent to the narrowed and occluded sinusoids. In degenerated and spotty necrotic cells, the positive signals from of ISH for EHFV RNA and those from immunostaining for the virus protein were both stronger than those in the zonal liver cell necrosis area. The results showed that hepatocellular degeneration and spotty necrosis might be directly related to the virus and its duplication inside the liver cells, while the zonal necrosis was ischaemic and thought to be caused by microcirculation dysfunction.