The dissertation contains a new approach to solving the scientific problem, diagnosis of chronic viral hepatitis C (CVHC) and involves determining the concentration of galectin-9 (Gal-9) in the serum of patients to determine the severity of liver fibrosis, the degree of inflammation, cirrhosis and splenomegaly, predicting the development of autoimmune disorders.
In order to improve the diagnostics of cirrhosis, prediction of immunological disorders in chronic viral hepatitis C based on the study of clinical, hematological, biochemical, integrative features depending on the regimen of antiviral therapy and galectin-9 concentration, patients were included in the study under the following conditions: the presence of chronic hepatitis C infection confirmed by PCR (qualitative). All patients examined by us signed informed voluntary consent for diagnostics and treatment (form № 003-6o). The study was conducted in four stages. In the first three stages, 287 patients with chronic viral hepatitis C and 55 practically healthy individuals who underwent preventive medical examination at the University Clinic of SSU were examined. In the fourth stage, the concentration of galectin-9 was determined in 68 infected and 20 people from the comparison group. All groups were representative by age and sex.
It was found that young people (47.74 %) and males (64.80 %) predominate in CVHC, with 1b HCV genotype (52.30 %), moderate liver fibrosis (31.36 %) and minimal activity (73.17 %) (p <0.05). Among the probable ways of infection indicated by patients predominate - dental treatment (61.67 %), surgery and manipulation (61.32 %). It is proved that in patients with hepatitis C virus (HCV) among the clinical symptoms, the most pronounced are asthenovegetative syndrome (81.88%) and a feeling of heaviness in the right hypochondrium (64.76%), on objective examination - hepatomegaly (74.21%) p <0.05).
The dependence of hematological changes on the antiviral therapy regimens (ATR) was established: after 4 weeks the number of leukocytes (1.5 and 1.6 times), erythrocytes (1.1 in both regimens) decreased and ESR increased in subjects receiving double and triple therapy (in 2.2 and 2.8), and with double therapy the number of platelets is further reduced (in 1,2) (p <0,05); when using direct antiviral drugs only the content of erythrocytes, hemoglobin decreases and ESR increases (p <0.05). In biochemical analysis of blood in all ATR reduces the activity of transaminases and total bilirubin.
Changes in integrative parameters in the infected indicate an increase in the degree of disorder of the leukocyte formula, the prevalence of cellular immunity (increased lymphocyte index), stress immunoreactivity and adaptive capacity for immune response (increased resistance coefficient), dominated by activation of the macrophage system (decrease neutrophil-monocyte ratio), the autoimmune component is strengthened in comparison with infectious (lymphocytic-granulocytic index and index of leukocyte and ESR ratio increase) (p <0,05). In patients with interferon-containing therapy there is an increase in immunoreactivity (increased lymphocyte index) and inflammation of autoimmune genesis (increased index of leukocyte and ESR ratio, lymphocytic-granulocytic index).
In subjects receiving IFN (pegylated interferon) + ribavirin and IFN + ribavirin + sofosbuvir, autoimmune processes increase after 12 weeks of treatment (increased ATPO and intermediate ANA and AMA positives). In all groups, the amount of Anti-Tg Ab does not change.
It is confirmed that increasing the values of F (METAVIR), FIB-4 and APRI increases the likelihood of telangiectasia, splenomegaly (p <0,05). The direct correlation of liver fibrosis with integrative indicators indicates an increase in infectious-inflammatory process (integral indicator of severity), confirms an increase in autoimmune processes (index of leukocyte and ESR ratio), decreased immunoreactivity (immunoreactivity index, neutrophil-monocyte ratio, lymphocyte - monocyte ratio) and increased leukocyte disorder (entropy).
An increase in the content of galectin-9 indicates an increase in the degree of fibrosis, since its concentration correlates with an increase in F (METAVIR), APRI, FIB-4 and a decrease in the number of platelets (p <0.05). The concentration of galectin - 9 above 3929 pg / ml indicates the development of liver cirrhosis (AUC = 0.813, Se - 75.0%, Sp - 81.2%), above 4829 pg / ml - splenomegaly (AUC = 0.944, Se - 100 %, Sp - 88.9%). The higher the concentration of galectin-9 for 4 weeks ATR, the more likely it is to detect positive ANA at 12 weeks. treatment (AUC = 0.773, Se - 75.0%, Sp - 68.7%).
