Polymorphism of promotor region of the tumor necrosis factor-alpha gene in patients with viral hepatitis C.

Study of the pathogenesis of viral hepatitis C is of primary importance because of persistence of this virus and high incidence of chronic course of this disease, and as a consequence, development of cirrhotic and neoplastic processes in the liver determining high mortality from this condition. Proinflammatory cytokines, in particular, tumor necrosis factor, play an important role in the development of these pathological processes. The content of tumor necrosis factor in the circulating blood plasma and hepatocytes increases in acute and chronic hepatitis C.

Chronic hepatitis C: modern notions of pathogenesis and morphogenesis. Concept of antiviral protection in hepatocytes.

Here we review modern notions about biological properties of hepatitis C virus, geographic distribution of its genotypes, peculiarities of immune reactions during chronic HCV infection, and role of viral replication in the infectious process. The concept of antiviral protection in liver parenchymal cells suggests suppression of biosynthetic reactions in hepatocytes resulting in inhibition of viral replication and focal degradation of the cytoplasm in infected cells followed by exocytosis and elimination of viral particles (cytosanation without cytodestruction). The recovery of structural characteristics in hepatocytes is associated with intracellular regeneration.

Is replication of hepatitis C virus a marker of activity of infectious process? (Findings of polymerase chain reaction and morphological analysis of liver biopsy specimens).

Comparative study of replication markers of hepatitis C virus in various biological substrates and evaluation of activity of chronic HCV infection in liver biopsy specimens showed that replication of hepatitis C virus and the number of HCV-infected hepatocytes did not promote liver damage in chronic hepatitis C. These findings indicate that the expression of antiviral reactions by liver parenchyma cells plays the key role in the morphogenesis of HCV infection.

Immunohistochemical, molecular, and pathomorphological study of liver biopsy specimens during chronic hepatitis C.

We carried out a comparative study of replication markers of hepatitis C virus (HCV RNA) in some biological substrates and NS3-antigen in liver biopsy specimens. It was found that 82% liver specimens contained RNA HCV, in 44% cases HCV RNA was present in the serum, mononuclear blood cells, and liver. The presence of NS3-antigen in hepatocytes can be considered as a structural marker of HCV replication, which is confirmed by positive correlation with the results of PCR for viral RNA in tissue specimens.

Molecular, genetic, and morphological markers during persistence of RNA-containing hepatitis C virus in the body.

A comparison of 5'-UTR structures in Siberian isolates of hepatitis C virus showed that the majority of genotyped samples had 1b genotype. A correlation was found between HLA antigens and their stable complexes and clinical manifestations of hepatitis C. We revealed immunogenetic criteria of organism's resistance or susceptibility to hepatitis C virus.