Ultrastructural reactions of liver cell populations induced by RNA-containing hepatitis C and DNA-containing hepatitis B viruses

Abstract

Combined hepatitis C and B virus infection is associated with phenotypic heterogeneity of hepatocyte populations. Patchy distribution of hepatocyte ultrastructural changes is due to the diversity of complex cytopathic effects of these viruses. RNA-containing hepatitis C virus impairs mainly the cytoplasmic compartment of liver parenchymal cells and does not affect the nucleus. DNA-containing hepatitis B virus induces degradation of the nuclear compartment. Key Words: viral hepatitis C+B; hepatocytes; endotheliocytes; alteration; electron microscopyThe problem of HCV+HBV coinfection is important for studying viral hepatitides. Viral replicative activity determines the intensity of structural reactions in hepatocytes, which is much higher in HBV than in HCV. The most considerable pathological changes accompany combined replication of both viruses [9].An extremely early appearance of virus-specific antigen in the hepatocyte cytoplasm is typical of hepatitis C [15]. Of particular interest is the localization of HCV structural proteins in hepatocytes. Immunohistochemical assay of the liver of transgenic mice expressing various levels of structural proteins demonstrated that core-and E2-proteins are primarily localized in the cytoplasm of hepatocytes [12].Liver biopsy in hepatitis C [4] showed high resistance of the nuclear compartment to HCV; its structure Laboratory of Ultrastructural Basics of Pathology, Institute of Regional Pathology and Pathomorphology, Siberian Division of the Russian Academy of Medical Sciences, Novosibirsk is preserved even after considerable degeneration and loosening of the cytoplasm [3,5]. By contrast, the degradation of hepatocyte nuclei with the formation of ringlike structures is typical of DNA-containing HBV [1].Here we performed a structural analysis of the nuclear and cytoplasmic compartments of hepatocytes and endotheliocytes in liver samples from patients with HCV+HBV coinfection verified by clinical, biochemical, immunoserological, and pathomorphological markers and confirmed by PCR, and compared these results with the data on HCV infection reported previously [4]. MATERIALS AND METHODSForty liver samples taken from 28 patients by transcutaneous biopsy were analyzed by light (paraffin and semithin sections) and electron microscopy. For light microscopy, the samples were fixed in 10% neutral formalin. Paraffin sections were stained by the van 0007 -4888/99/0007-0747522.00 9Kluwer Academic/Plenum Publishers