Alteration and intracellular regeneration of hepatocytes under the effect of hepatitis C virus

Abstract

In chronic virus hepatitis C, two types of structural changes dominate in hepatocytes: multivesicular lipid infiltration and cell involution degeneration characterized by reduction of all cytoplasmic organelles and light-optic phenomenon of cytoplasma depletion with preserved structure of the nuclear compartment. These changes can be considered as adaptive cell response to cytopathic influence of hepatitis C virus. Key Words: hepatitis C virus; hepatocytes; degeneration; regeneration; pathomorphologyHepatitis C virus (HCV) genome contains single-strand RNA encoding structural and nonstructural viral proteins. HCV infection, one of the most common cause of morbidity and mortality in the world [8], induces a wide spectrum of liver disorders from silent carrier state to fatal hepatic insufficiency. HCV infection is characterized by a higher rate of transformation to chronic disease in comparison with other hepatotropic viruses. HCV infection is also associated with the development of hepatocellular carcinoma [ 13].The role of viral cytopathic effects remains poorly understood, since experimental models, in particular transgene expression of HCV structural proteins, revealed no histological changes related to the expression of these proteins in animals [12].The aim of the present study was to analyze cell and intracellular reactions of the liver in chronic hepatitis C verified by clinical, biochemical, and immunoserological tests. MATERIALS AND METHODSAutopsy materials (46 samples) from 37 patients with chronic hepatitis C obtained through transcutaneous Laboratory of Ultrastructure Basis of Pathology, Institute of Regional Patholo~jy and Pathomorpholo9y, Siberian Division of the Russian Academy of Medical Sciences, Novosibirsk biopsy were analyzed. Each specimen was divided into 2 parts: the larger part was used for preparing paraffin sections, while the lesser samples were used for preparing semithin and ultrathin sections.For light microscopy, the specimens were fixed in 10% neutral formalin. Paratfin sections were stained with hematoxylin and eosin followed by Perls' reaction, according to van Gieson method combined with visualization of elastic fibers with Weigert resorcin-fuchsin, and PAS reaction was carried out.Electron microscopy specimens were fixed in 4% paraformaldehyde and processed routinely [2]. Semithin sections were stained with azur II and Schift reagent. Ultrathin sections were contrasted with uranyl acetate and lead citrate and examined under a JEM-1010 electron microscope.Stereological analysis of liver specimens was based on counting the test system points within the test structure [7,11]. Tissue structure was assessed on semithin sections. Structural density of different parenchymal and stromal components (hepatocytes, endotheliocytes, sinusoids, stroma, and cell infiltrates) was measured using an ocular test system consisting of short lines (n=36, P=72, L=650 la) and derivative stereological parameters (stroma to parenchyma and vessels to parenchyma ratios) were calculated. The differences wer...

Histopathology and ultrastructure of the liver under combined action of narcotics and hepatitis C and B viruses

“…Thus, combined action of opiates and hepatitis C and B viruses induced structural changes in the hepatic tissue, which by their light microscopic characteristics did not significantly differ from those described previously for hepatitis C and C+B [4,5]. However, some tissue and structural changes were probably associated with metabolism of narcotics.…”

“…Numerous experimental and clinical studies analyze the effects of narcotics alone [1,9,11,12] or in combination with hepatitis [13-15] on animal and human liver. However, there are only few reports on combined action of opium and hepatitis viruses [10].Previously, we reported structural reactions of the liver induced by chronic hepatitis C and C+B [4,5]. Here we present the results of examination of liver autopsy material from intravenous opium addicts suffering from chronic hepatitis C and C+B.…”

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

“…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].…”

“…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].…”