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Usually, the efficacy of antifibrotic drugs is evaluated using laboratory animals. As the modern scientific literature shows, there is still a number of unsolved problems. First, it is necessary to determine the appropriate models that are able to reflect most accurately the development of fibrosis and cirrhosis in humans. Second, to identify diagnostic and prognostic markers to assess the progression / regression of fibrosis in animals. Third, to examine carefully the generally accepted scales for the semi-quantitative assessment of fibrosis in animal models. Based on the findings obtained, we offer an experimental model that has a number of advantages over others. In rats, thioacetamide induces fibrogenesis followed by transformation into cirrhosis. The model allows the study of fibrosis sequentially or at specific stages and is easily reproducible. The developed morphological scale describes fibrogenesis in detail, takes into account intermediate stages, and possesses a diagnostic and prognostic value.

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Developing liver disease treatments, in which fibrosis is a key pathogenetic link, still remains an urgent problem in hepatology. In the present study, the level of mmp-9 mRNA expression and the number of FAP+, -SMA+, CD45+ cells were analyzed at nine time points of fibrosis and cirrhosis. It was found that in the case of liver fibrosis, the choice of the optimal reference gene depended on the stage of fibrogenesis. When studying the specific stages rather than the entire process in a long-term experiment, it was shown that choosing an optimal reference gene has to be done additionally. In this case, the mmp-9 mRNA expression level should be considered as a marker of liver fibrosis initiation and development but not as that of cirrhosis progression. In the liver, two morphologically heterogeneous populations of myofibroblasts were simultaneously identified as able to synthesize various types of immunohistochemical markers. It was found that the FAP+ cells were the main contributor to the development of portal fibrosis and the initial stages of bridging fibrosis. In the selected experimental model, fibrosis initiation and the development stages preceding parenchyma restructuring were accompanied by a low level of inflammation.