A study of pathogenesis of viral hepatitis by quantitative analysis

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ICR mice inoculated with mouse hepatitis virus, MHV-2S, -2M, -2L and athymic nude mice inoculated with MHV-2cc were used as models of acute and chronic viral hepatitis, respectivelyAt first, the examination was carried out in the former experimental system, mainly in lymphatic organs such as the thymus, lymph nodes and spleen, using an image analyzer system (PIAS III). The lesions became severer in accordance with the decrease of Thy-1 positive cells and it was demonstrated that the damage of the lymphoid organs was one of the causes that made hepatitis severer.Viral antigen in the liver was formed in both some hepatocytes and Kupffer cells and widely spread to most of hepatocytes. In an experiment using low virulent mutants (MHV-2S and -2M) revealed that small focal lesions were formed in the early stage, then became severer.In the chronic hepatitis using the system athymic mice and low virulent mutants of MHV, mice inoculated with MHV-2L, the lowest virulence, showed gradual enlargement of lesions and made chronic infiltrating hepatitis. By inoculation of the other mutants, viral titer increased rapidly showing those were unsuitable for making the model of chronic hepatitis.Increase of areas of hepatic lesions by calculation with the image analyzer changed with the severity of hepatic lesions those showed the utility of the image analyzer for evaluation of the hepatic lesions.To evaluate the effects of interferon in chronic hepatitis, the system of athymic mice and MHV-2cc was used. In a group of mice seriously administered with interferon from the time of viral inoculation, viral titer, the value of hepatic enzyme and areas of hepatic lesion were well corelated, those demonstrated that the image analyzer system made possible to evaluate the lesion of chronic hepatitis quantitatively.