Shevchenko-Makarenko O. Stratification of clinical-epidemiological and epigenetic factors for the personalization of management of patients with chronic viral hepatitis C

The work is performed in several stages. At the first stage, studies were conducted to determine the prevalence and incidence of HCV in the Dnipropetrovsk region compared with data for Ukraine. The incidence, prevalence and mortality from comorbidities and liver damage in certain groups, including patients with HIV / hepatitis coinfection, were studied. Comorbid conditions in a cohort of 4169 patients with chronic viral hepatitis C were studied and the risks of HCV-associated cirrhosis of the liver and hepatocellular carcinoma and mortality from this pathology were identified. An in-depth comprehensive examination was performed in 841 patients with chronic viral hepatitis C, who were assigned various antiviral therapy regimens and assessed sustained virological response - 24. Epigenetic markers were studied in 74 patients with HCV, namely miRNA-29a, miRNA-196a, miRNA-122 and criteria for differentiation between patients and healthy individuals by their level were determined. ROC-analysis of the prediction of antiviral therapy success was performed based on the baseline level of expression of these markers depending on the experience of previous therapy in patients using the expression level of miRNA-196a, and a patent for a useful model was obtained. Criteria for differentiating the stages of liver fibrosis F1 and F4 by the level of miRNA-29a expression were created. The Chronic Liver Disease Questionnaire in ukrainian (CLDQ-U) questionnaire was adapted in Ukrainian as a research tool for personalizing the management of patients with chronic viral hepatitis C. The Information Letter was received and implemented in the practical health care system. For the first time, new scientific data on the clinical and pathogenetic role of epigenetic factors in the development and course of HCV, which are significantly associated with probable HCV infection (p<0.001) were obtained. The level of miRNA-29a expression has been shown to be significantly associated with the severity of liver fibrosis from F1 to F4 in patients with chronic viral hepatitis C. Scientific data on clinical and laboratory predictors of development or mortality from HCV-associated cirrhosis of the liver and hepatocellular carcinoma were supplemented. Scientific data on the informativeness of calculators for non-invasive determination of the level of liver fibrosis (APRI, FIB4, GUCI, LOC, MELD, Forns, MDA) and epigenetic markers in the diagnosis of liver fibrosis at stage F4 in chronic viral hepatitis C patients in comparison with the results of liver fibroelastometry have been advanced. The prognostic information value of clinical and laboratory markers of the rate of progression of liver fibrosis in patients with chronic viral hepatitis C has been adjusted. Scientific data on the influence of various factors on the indicators of quality of life, anxiety and depression in patients with chronic viral hepatitis C have been supplemented. It has been proven that the progression of the degree of liver fibrosis, regardless of the HIV status of patients with chronic hepatitis C, negatively affects the indicators of the quality of life (p<0.05). The main risk factor for anxiety and depression in patients with chronic viral hepatitis C during antiviral therapy (AVT) is the use of treatment regimens containing interferon. The cascade of services for patients with HCV in the Dnipropetrovsk region was evaluated and the effectiveness of therapy according to different AVT schemes was determined. The Register of Chronic Viral Hepatitis Patients in the Dnipropetrovsk region has been created and optimized and its implementation at the national level as a tool for implementing the global Strategy for the elimination of viral hepatitis in the world and for better management of HCV patients with a personalized approach to each patient. Further development was performed by the clarification of the main epidemiological and socio-demographic features of the epidemic process of HCV-infection in the Dnipropetrovsk region.