ИСТИНА

Introduction. Nowadays, much attention is paid to the search for genetic factors which can explain the course of chronic hepatitis C (CHC). Hypercoagulation plays an important role in the progression of liver fibrosis, but the influence of coagulation encoding genes and pathways on the rate of the disease progression is poorly understood. AIM: In this study we assess the prognostic and clinical value of the presence of different gene polymorphism combinations including FII 20210 G/A, FV 1691G/A, FVII 10976 G/A, FXIII 103 G/T, ITGA2 807 C/T, ITGB3 1565 T/C, FBG -455 G/A, PAI -675 5G/4G, MTHFR 677 C/T on fibrosis progression in patients with chronic hepatitis C (CHC). SUBJECTS AND METHODS: 187 patients with CHC were categorized as «fast» (fibrosis rate progression ≥0,13 fibrosis units/yr, n=89) and «slow» (fibrosis rate progression < 0,13 fibrosis units/yr, n=88) progressors. Assessment of gene polymorphisms was carried out by PCR quantification. RESULTS: Genotype GA FV 1691G/A was more commonly observed in the group of «fast progressors» compared to the group of «slow progressors» (10,11% vs 1,14%, OR=9,787, p=0,011). A trend for the minor A allele FV 1691 G/A was more frequently observed in the group with progressive fibrosis than in the group with a slow fibrosis progression rate (1,7% vs 5,56%, p=0,139). Genotype GA FII 20210 G/A and genotypes with 4G allele (5G4G + 4G4G) and 4G allele PAI -675 5G/4G were also more common in «fast progressors» compared with «slow progressors», the frequency of detection of this genotype had a trend to statistical significance (p=0,118, p=0,112 and p=0,117 respectively). No associations were found between polymorphisms in rhw other genes and fibrosis rate. An integrated model of coding "profibrogenic" genotypes (FV 1691 G/A, FII 20210 G/A, PAI-I -675 5G/4G) showed that rate of liver fibrosis progression (units fibrosis/year) increased with total score (p=0,039), indicating on combined effect of these genes. CONCLUSION: We have shown that the presence of mutant genotypes FV 1691 G/A, FII 20210 G/A, PAI-I -675 5G/4G is a factor that are associated with rapid fibrosis progression in chronic hepatitis C patients.