Romanchuk K. The Personalization of Pharmacotherapy and Its Prognosis in Patients with Chronic Hepatitis C

The dissertation is devoted to the prognostic role of polymorphic variants of IL-28B and IFNL4 on the effectiveness of antiviral therapy in patients with chronic hepatitis C. In the thesis the definitions of predictive factors of efficacy of antiviral therapy in patients with CHC are given. They are based on the evaluation of clinical, biochemical, serological, molecular-biological and molecular-genetic (rs 12979860 gene polymorphism IL-28B and ss 469415590 polymorphism of IFNL4) indices and morphological changes in the liver tissue. On the basis of a comprehensive survey the clinical features of chronic hepatitis C have been identified, depending on the carrier of different combinations of allelic variants of IL-28B and IFNL4 genes. It has been found that in patients with CHV C/C the genotype of the IL-28B gene was met 1.54 times less than in healthy people. Patients with T/T genotype of the gene IL-28B complained of fatigue 1,98 times more often than carriers of the C/C genotype. The presence of teleangiectasy was 2.4 times more prevalent in C/T genotype of the gene IL-28B than C/С. It has been proved that there are higher indicators of cytolysis, cholestasis and low initial viral load in the C/C genotype carrier of the gene IL-28B. Carriers of C/T genotype had 1.55 and 1.11 times higher level of alfa-fetoprotein compared to T/T and C/C genotypes. The largest number of patients with minimal necro-inflammatory activity in the liver tissue were the carriers of the T/T genotype of the gene IL-28B,whose share was 2.02 times higher compared to the native C/C genotype. The efficacy of the combined antiviral therapy in CHC has been evaluated according to different combinations of the allelic variants of IL-28B and IFNL4 genes. It has been established that the SVR was achieved 3.03 times more frequently in patients with CHC who were the carriers of the TT/TT genotype of the IFNL4 gene than in carriers of the G/G genotype. SVR were 1.9 and 3.2 times more often achieved in carriers of C/C genotype of the IL-28B gene, compared to patients with CHV who were the carriers of the C/T and T/T genotypes. The predictive probability of achieving SVR by patients with CHC with genetic and clinical determinants has been established based on the MCMC model.