The dissertation is devoted to increasing the effectiveness of diagnosing liver fibrosis in patients with chronic diffuse liver disease (CDLD) by substantiating new differentiated informative invasive, minimally invasive and non-invasive approaches taking into account etiological factors and, on the basis of developed experimental models, substantiating new methods of treatment aimed at regression of liver fibrosis. The work consisted of two directions – clinical and experimental. The first direction (clinical) provided for improving the effectiveness of invasive, minimally invasive and non-invasive approaches to the determination of fibrotic changes in the liver in patients with HDP, depending on the etiology of the disease. The second direction (experimental) involved the development of experimental models and the justification based on them of new methods of treatment aimed at the regression of liver fibrosis. For the first time, new differentiated approaches to the diagnosis of liver fibrosis in CDLP patients were developed, taking into account the etiology of the disease by determining the level of serum biomarkers, which in terms of sensitivity and specificity prevail over the existing traditional ones.Scientific data on the specifics of immunological changes in relation to fibrosis in the liver in patients with CDLP of various etiologies have been clarified. It has been proven that all patients with CDLP, regardless of the etiological factor, have a suppression of cellular immunity, which is characterized by a lower content of CD3 and CD4 lymphocytes than in healthy people in the absence of changes in the content of CD8 lymphocytes, and a decrease in the immunoregulatory index in NAFLD and CHC. It was clarified that the content of CIC is the highest in ALD and TG compared to both healthy people and patients with NAFLD. Direct correlations of the level of CIC with the activity of ALT and AST in the group of patients with NAFLD were revealed. The scientific evidence that immunosuppression at the cellular level is combined with signs of cytokine imbalance, the expressiveness of which depends on the etiology of CDLP, has been expanded. In CHC, changes in these parameters are most pronounced due to the higher content of pro-inflammatory cytokines IL-6 and TNF-α, compared to CDLP of non-viral etiology. Interrelationships of IL-10 content with parameters reflecting the formation of fibrotic changes in the liver have been proven, namely: in ACP with the endotoxicosis marker - MMP, in TG - with the level of HOMA-IR. Added scientific data on the peculiarities of morphological and morphometric indicators in patients with CDLP depending on the etiology of the disease. It has been demonstrated that the morphometric indicator of the liver fibrosis index is higher in patients with ACP, compared to both patients with NAFLD and patients with CHC. The threshold level of the computerized fibrosis index (CIF) was determined, which confirms the presence of liver fibrosis in patients regardless of the etiology of CDLP. Insights into the effectiveness of non-invasive approaches to the determination of fibrotic changes in the liver in patients with CDLP, depending on the etiology of the disease, have been deepened. It is shown that, according to the data of SWE, in CHC and ALD, the liver parenchymal stiffness index (LST) is higher than in NAFLD, which is confirmed by an increase in the frequency of registration of METAVIR F3-4 stage liver fibrosis in CHC and ALD, than in NAFLD and TG. According to TE data, a higher value of the LSM indicator was found in patients with CHC and ALD compared to NAFLD and TG, which is accompanied by a higher frequency of F4 liver fibrosis stage registration in CHC and ALD than in NAFLD and TG. Added scientific data on the association of the LSP indicator with clinical and laboratory characteristics, namely: with NAFLD - with body mass index (BMI) and AST; with ALD - with HOMA-IR level; with TG - with the level of platelets and triacylglycerides (TAG). It has been proven that the use of SWE is more effective than TE in patients with CDLP in the diagnosis of the severity of liver fibrosis due to greater sensitivity and specificity. Experimental models have proven the possibility of achieving an antifibrotic effect in non-viral genesis of liver damage after the cessation of the etiological factor. Following data indicates a high probability of liver fibrosis in patients with ALD: TNFα, HPb/z, GAG. Following data allows to verify liver fibrosis in patients with TH: MMP content is IL-6/IL-10, coefficient of СD4+ /СD8+.The definition of liver fibrosis was developed and implemented for patients with NAFLD; for patients with CHC.
