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Introduction. Recently, a negative trend of increasing the levels of prevalence, disability and mortality caused by chronic viral hepatitis C (HCV) infection has been determined. Around the world is defined 0.6-10.0 % suffer from chronic HCV (about 71 million with an annual increase of 1.75 million cases). Even higher are the levels of HCV seropositivity, which according to the WHO are about 100 million people (1.6 % of the world population). The WHO identified the need to improve the diagnosis of chronic HCV and to identify its asymptomatic forms and irreversible consequences (liver fibrosis and liver cirrhosis). Increasing the effectiveness of existing and developing new diagnostic approaches to improve early detection of chronic HCV and its consequences (liver fibrosis) is an urgent issue. The aim. To determine the prognostic possibilities of blood markers for the diagnosis of the development of the fibrotic process in chronic viral hepatitis C. Materials and methods. 78 people were examined: 47 (main group) – with chronic HCV and 31 – without chronic HCV (comparison group). Results. Probable associations with increased risks of development of LF in chronic HCV were: increased Mean Corpuscular Volume (MCV) (OR=4.305; 95.0 % CI 1.187-15.619; p=0.026) and Platelets (OR=0.955; 95.0 % CI 0.922-0.989; p=0.011), which indicated increased chances of developing LF in chronic HCV when exceeding the standard MCH indicators (by 4.305 times) and reduced chances – when increasing Platelets (on 4,5 %). Conclusions. Based on the research, it was determined that blood markers can be used as a significant predictor of the development of LF of patients with chronic HCV. Increased levels of MCH and Platelets in blood serum characterize a significant relationship with the development of LF in patients with chronic HCV, which indicates a significant influence of blood markers on the pathogenesis of LF in patients with chronic HCV.

Scientific relevance. Direct-acting antivirals have significantly improved the effectiveness of treatment for hepatitis C. However, Russia and the Eurasian Economic Union lack recommendations for the clinical development of medicinal products from this pharmacotherapeutic group.Aim. The study aimed to analyse the requirements and recommendations for planning safety and efficacy clinical trials of direct-acting antivirals for chronic viral hepatitis C, outlined in the regulatory documents of the European Union and the United States.Discussion. Upon analysing the requirements and recommendations, the authors explained the reasons behind choosing the target population and the design for the efficacy and confirmatory studies. The article covers the clinical development of direct-acting antivirals in special populations, including patients with hepatitis C and HIV co-infection, a liver transplant, and prior treatment experience. According to the authors, patients who achieved a sustained virological response should be followed up for a full year after the end of treatment in order to confirm the durability of their response. A dose-finding study should first identify a suitable dose range for monotherapy and, subsequently, for combined therapy. Current treatment regimens should be optimised, and studies should be conducted to reduce treatment duration.Conclusions. The authors outlined the main approaches and a methodology for clinical trial programmes that should take into account the degree of correlation between the efficacy of direct-acting antivirals and the genotype/subtype of hepatitis C virus.

The global pandemic of the new coronavirus infection (COVID-19), which began in December 2019 in Uhan (China), has spread worldwide. On 11 March 2020, the World Health Organization announced the outbreak of the SARS CoV-2 pandemic due to the constant number of cases outside China. Rapid and decisive measures are being taken in our country to effectively combat the coronavirus pandemic, which is spreading rapidly around the world. Particular attention is paid to such important aspects as preventing the spread of coronavirus infection, effective treatment of patients with the disease, and conducting laboratory tests. Patients with chronic liver diseases required increased attention of doctors during the epidemic, since against the background of an exacerbation of their diseases, not only the risk of contracting a viral infection of COVID - 19 increased, but also its aggravation. (Mekhtiev.S.N and co-author. 2020). Severe liver damage during the severe course of COVID - 19 is diagnosed with a severe course of the disease. Patients with COVID - 19, confirmed by serious liver damage, experience an increase in high biochemical indicators. At the height of the disease, thrombocytopenia is observed. An increase in serum aminotransferase, creatinkinase and lactatdegydrogenase activity is detected. Literature has shown that patients with severe covid - 19 manifestations are at higher ALT levels, lower platelet and albumin numbers, and higher risk of death. Data analysis shows that the frequency of cases of impaired liver function increases in proportion to the severity of COVID-19 flow. Apparently, an increase in alt, hypoalbuminemia and thrombocytopenia are unfavorable factors in the prognosis of the disease. Analysis of the clinical picture of COVID-19 has shown that SARSCoV-2 has significant effects for SJK (chronic liver diseases). Patients with viral etiology are more susceptible to liver damage, which is likely due to increased replication of hepatitis V and C viruses during SARSCoV-2 infection. The presence of an Associated side disease (diabetes, cardiovascular diseases) tends to develop a severe form of COVID-19 in patients. Today, there is no clear data on whether patients with chronic hepatitis C have a higher risk of contracting COVID-19 compared to other diseases. At the same time, serious complications, if it is not possible to prevent COVID-19 infection, then the disease develops rapidly in them. Even if hepatitis C has been successfully treated in particular, it increases the chances of severe covid-19 passing. Therefore, against the background of the COVID-19 pandemic, the problems of patients with chronic viral hepatitis C are unresolved and require study. In epidemic conditions, it is very important to effectively monitor patients with this pathology and continue to treat them health, as well as to carry out scientific research to reduce the problem in the health system and reduce the disease. [ABSTRACT FROM AUTHOR]

Background. Diagnosis of an asymptomatic course of chronic viral hepatitis C (HCV) and the existing development of the fibrotic process by determining the marker capabilities of biochemical blood parameters (primarily osteopontin — OP) is an urgent issue in modern medicine. Purpose: to evaluate the prognostic value of biochemical blood markers for diagnosing an asymptoma­tic course of HCV and the existing fibrotic process. Materials and me­thods. Seventy-eight people were examined: 47 from the main group — 19 (40.4 %) women and 28 (59.6 %) men with chronic HCV, and 31 controls — 17 (54.8 %) women and 14 (45.2 %) men without chronic HCV. The median, as well as 25.0% and 75.0% quartiles and relative values were calculated for quantitative and qualitative measures, respectively. Predictors were determined using logistic regression analysis. Results. The data obtained by a univariate analysis indicate a significantly increased risk of develo­ping liver fibrosis on the background of chronic HCV, with alanine aminotransferase (ALT) levels increased by 1.037 times, aspartate aminotransferase (AST) by 1.051 times, gamma-glutamyl transferase (GGT) by 1.017 times; thymol turbidity test by 1.424 times; total protein by 1.162 times and OP by 3.002 times. With increased levels of triglycerides and very low-density lipoproteins, a significant decrease in these risks was found, by 74.7 and 94.7 %, respectively. A multivariate analysis found significantly increased risks of deve­loping liver fibrosis on the background of chronic HCV, with higher levels of AST, total protein, and OP (by 1.028, 1.195 and 2.510 times, respectively). Conclusions. With a significant liver damage by a fibrotic process (stage 3–4), as compared to stage 0–2, there is a probable predominance of biochemical liver markers in the blood of patients with HCV: ALT, AST, GGT, total protein and OP. AST, total protein, and OP were identified as reliable predictors of liver fibrosis. The developed mathematical model has high sensitivity and specificity: 87.5 and 83.9 %, respectively.

Background. Viral hepatitis C (HCV) is not only as a liver disease but also as a systemic (generalized) infection that affects ot­her organs, in particular, the pancreas and gastroduodenal zone. The state of the gastrointestinal mucosa in combined course of chronic pancreatitis (CP) and chronic HCV is little studied, but extremely relevant, as it is important for the clinical course, the quality of life of patients, as well as for assessing the safety of the performed (etiotropic, etc.) and planned restorative comprehensive treatment of such patients. The purpose is to evaluate the morphological changes of the gastroduodenal mucosa of patients with chronic pancreatitis associated with chronic viral hepatitis C who were treated etiotropically. Materials and methods. Thirty patients with CP and 65 patients with CP in comorbidity with chronic HCV after etiotropic treatment of HCV were examined. Regardless of the HCV genotype, they received a course of treatment with sofosbuvir at a dose of 400 mg and velpatasvir 100 mg in the morning after meals for 3 months (some patients took daclatasvir at a dose of 60 mg also in the morning after meals for 3 months instead of velpatasvir). The period after diagnosed and treated HCV before the examination was on average (2.35 ± 0.61) years. All patients underwent a morphological study of gastric and duodenal biopsy samples obtained by esophagogastroscopy. The prepared samples were evaluated according to the international OLGA and OLGIM systems based on the evaluation of 5 gastric biopsies (1 from the corner of the stomach, 2 from the body, and 2 from the antrum) with a description of the main pathomorphological changes evaluated on a visual analog scale. Alcian yellow and toluidine blue were used to detect H.pylori. An own system for assessing the morphological state of the gastroduodenal mucosa was also proposed. Results. The detected structural changes indicate the presence of chronic atrophic gastritis with moderate dysplasia of the glandular epithelium. Stage of chronic gastritis according to the OLGA system was III. Stage of chronic gastritis according to the OLGIM system was III. Thus, the practically asymptomatic course of quite significant gastroduodenal changes in CP combined with chronic HCV requires additional therapeutic influence, as well as an assessment of comprehensive treatment based on the effect on the gastroduodenal mucosa. In case of changes in gastroduodenal mucosa in CP on the background of chronic HCV, in contrast to those with isolated CP, a significantly higher level of inflammatory infiltrate density (moderate (2+) vs. mild (1+)) is determined, which is accompanied by moderate neutrophilic infiltration (2+) vs. mild (1+) and mild lymphohistiocytic infiltration (1+) versus no such infiltration (0), the appearance of intestinal metaplasia (2+) and moderate non-metaplastic glandular atrophy (2+) versus the absence of metaplasia (0) and mild non-metaplastic glandular atrophy (1+), as well as zones of metaplastic atrophy (1+), which was manifested by the appearance of Paneth cells and goblet cells. In CP with chronic HCV, mucosa has atrophic changes. Metaplasia is manifested by a change in cellular phenotype: complete intestinal metaplasia type I–II is manifested by the appearance of Paneth cells and goblet cells; incomplete — by the presence of columnar epithelium and goblet cells; colonic metaplasia — by enlargement of the glands and the absence of Paneth cells. Conclusions. It was proved that the state of the gastric and duodenal mucosa in the group of patients with CP and chronic HCV was significantly severe than that in isolated CP: lymphohistiocytic infiltration of the mucous membrane was detected 2.68 times more often, non-metaplastic infiltration glandular atrophy (there was practically no glandular atrophy in the group of isolated CP) — 12.65 times more often, metaplastic atrophy (it was not detected in the group of CP) — 10.64 times more often, acute leukocyte infiltration — 2.31 times more often, dysplasia of the mucosal epithelium (with isolated CP, mild dysplasia was detected) — 7.30 times more often, erosion of the mucosal epithelium — 3.07 times more often, focal hyperplasia of the glands — 3.88 times more often, intestinal metaplasia — 12.89 times more often, which was practically absent in CP. In general, the total number of pathological signs of the mucous membrane in the group of CP with comorbid chronic HCV was found to be 2.76 times higher than that in isolated CP.

Objective was to conduct a comparative analysis of routine clinical and laboratory parameters in two groups of patients with chronic viral hepatitis C (CHC) depending on the presence or absence of hepatic steatosis.Methods and materials. The observational retrospective cross-sectional study included 411 patients with CHC, of which 43.80 % were those with hepatic steatosis. The studied parameters were routine clinical and laboratory parameters, the viral genotype, as well as formalized results of a liver biopsy and ultrasound examination of the abdominal organs. To assess the differences between the two groups, the following were calculated: Pearson’s test, two-tailed Fisher’s test, Wilcoxon rank sum test, Spearman’s correlation coefficient, and partial correlation coefficient.Results. It was found that CHC patients with hepatic steatosis were older and had a higher body mass index (BMI) than patients without hepatic steatosis (p

Background. It was found that in 35–56 % of patients, hepatobiliary diseases are considered to be a factor causing the formation or exacerbation of chronic pancreatitis (CP) while reducing the share of pancreatitis of alcoholic etiology, as it was previously believed. However, the role of the alcohol factor and its consideration in the treatment strategy for CP and comorbidity with chronic viral hepatitis C (HCV) also needs to be clarified, because it is known that excessive alcohol consumption and smoking increases the risk of developing pancreatitis by 8–17 times. The purpose is to conduct a comparative analysis of parameters of the structural and functional state of the liver and pancreas in patients with chronic pancreatitis associated with chronic viral hepatitis C treated etiotropically, depending on the results of testing according to the international CAGE questionnaire. Materials and methods. We have examined 100 ambulatory patients with CP and concomitant HCV, treated etiotropically. All patients were examined according to generally accepted algorithms. To clarify the effect of alcohol on the formation of CP and the state of patients with treated HCV, latent craving for alcohol was verified using the international CAGE questionnaire. The study on the density of the liver parenchyma and the pancreas was carried out not only according to the ultrasound data in the B-mode, but also with the simultaneous shear wave elastography on the Ultima PA scanning ultrasound device with the further measurement of the median of the parameters in kilopascals. Determination of the pre­sence and depth of exocrine pancreatic insufficiency was carried out by the content of fecal elastase-1 evaluated using the enzyme immunoassay method. Results. Screening-testing of patients with CP on the background of HCV treated etiotropically using the CAGE scale made it possible to state that 65.0 % of them had a latent craving for alcohol, and 21.0 % of this cohort were women, which needs to be taken into account in the management of such patients. It has been proven that in the group with CAGE ≥ 2.0, functional and structural changes in the liver and pancreas were significantly more severe (deepening of the exocrine pancreatic insufficiency with a decrease in fecal α-elastase by 13.01 %, an increase in the total index of the coprogram by 15.11 % and the total ultrasound indicator of the pancreatic structure by 28.06 %, and the total ultrasound indicator of the liver structure by 40.68 % (р

Method: Etiological, gender, age and laboratory characteristics of chronic viral hepatitis C (CVHC) were studied and analyzed. The distribution of patients depending on the virus genotype, the activity degree and the severity of liver fibrosis were found out. Indices of non-specific reactivity, endogenous intoxication and inflammation in the course of CVHC, their dependence on treatment were studied. Correlations between the values of non-specific reactivity, endogenous intoxication, inflammation and patients' affiliation to the group of injecting drug users, the APRI score, the stage of liver fibrosis and the virus genotype were estimated. Significant increase in endogenous intoxication (LII, HII, ISS), non-specific immunoreactivity (IR, LMR, Ilymph, IA) and inflammation (ILG) at decrease in some endogenous intoxication indices (ISL, NRR) and inflammation (KI, ILESR) in patients with CHCV compared with healthy persons were established. Result: The decrease in endogenous intoxication indices (LII; HII; ISL; ISS; NRR) were observed during antiviral treatment. Such unambiguous reaction of non-specific immunoreactivity indices and inflammation indices were not observed: some of them increased (IIlymph, IA), some of them decreased (IR, NLR; ELR). KI decreased during the treatment, but ILG increased. Direct correlation between patients' affiliation to a group of injecting drug patients and the values of HII, NRR (p<0.05), between the APRI score and IIlymph level (p<0.05) was identified. Conclusion: No correlation between the indices values and fibrosis severity (according to METAVIR) and virus genotype was found. [ABSTRACT FROM AUTHOR]

Background. Diagnosis of an asymptomatic course of chronic viral hepatitis C (HCV) and the existing development of the fibrotic process by determining the marker capabilities of biochemical blood parameters (primarily osteopontin — OP) is an urgent issue in modern medicine. Purpose: to evaluate the prognostic value of biochemical blood markers for diagnosing an asymptomatic course of HCV and the existing fibrotic process. Materials and methods. Seventy-eight people were examined: 47 from the main group — 19 (40.4 %) women and 28 (59.6 %) men with chronic HCV, and 31 controls — 17 (54.8 %) women and 14 (45.2 %) men without chronic HCV. The median, as well as 25.0% and 75.0% quartiles and relative values were calculated for quantitative and qualitative measures, respectively. Predictors were determined using logistic regression analysis. Results. The data obtained by a univariate analysis indicate a significantly increased risk of developing liver fibrosis on the background of chronic HCV, with alanine aminotransferase (ALT) levels increased by 1.037 times, aspartate aminotransferase (AST) by 1.051 times, gamma-glutamyl transferase (GGT) by 1.017 times; thymol turbidity test by 1.424 times; total protein by 1.162 times and OP by 3.002 times. With increased levels of triglycerides and very low-density lipoproteins, a significant decrease in these risks was found, by 74.7 and 94.7 %, respectively. A multivariate analysis found significantly increased risks of developing liver fibrosis on the background of chronic HCV, with higher levels of AST, total protein, and OP (by 1.028, 1.195 and 2.510 times, respectively). Conclusions. With a significant liver damage by a fibrotic process (stage 3–4), as compared to stage 0–2, there is a probable predominance of biochemical liver markers in the blood of patients with HCV: ALT, AST, GGT, total protein and OP. AST, total protein, and OP were identified as reliable predictors of liver fibrosis. The developed mathematical model has high sensitivity and specificity: 87.5 and 83.9 %, respectively. [ABSTRACT FROM AUTHOR]

Sustained viral response (SVR) significantly improves the prognosis in patients with hepatitis C virus (HCV) chronic infection but does not totally alleviate the risk of liver‐related complications (LRC). We aimed to evaluate whether the dynamics of multiple measurements of simple parameters after SVR enable the development of a personalized prediction of prognosis in HCV patients. HCV mono‐infected patients who experienced SVR in two prospective cohorts (ANRS CO12 CirVir cohort: derivation set; ANRS CO22 HEPATHER cohort: validation set) were included. The study outcome was LRC, a composite criterion including decompensation of cirrhosis and/or hepatocellular carcinoma. Joint latent class modelling accounting for both biomarker trajectory and event occurrence during follow‐up was developed in the derivation set to compute individual dynamic predictions, with further evaluation in the validation set. In the derivation set (n = 695; 50 LRC during the median 3.8 [1.6–7.5] years follow‐up), FIB4 was identified as a biomarker associated with LRC occurrence after SVR. Joint modelling used sex and the dynamics of FIB4 and diabetes status to develop a personalized prediction of LRC. In the validation set (n = 7064; 273 LRC during the median 3.6 [2.5–4.9] years follow‐up), individual dynamic predictions from the model accurately stratified the risk of LRC. Time‐dependent Brier Score showed good calibration that improved with the accumulation of visits, justifying our modelling approach considering both baseline and follow‐up measurements. Dynamic modelling using repeated measurements of simple parameters predicts the individual residual risk of LRC and improves personalized medicine after SVR in HCV patients. [ABSTRACT FROM AUTHOR]

Recently, in medicine, the influence of infectious, hepatobiliary, gastric and duodenogenic factors for the formation and course of chronic pancreatitis (CP) and chronic hepatitis C virus (CHCV) which was treated etiotropically is increasingly being studied. Hepatitis C virus (HCV) is an important infectious factor in CP, for which the ability to chronic course has been proven. The condition of the mucous membrane of the organs in the gastroduodenal zone (GDZ) in the combined course of CP and HCV is important for the patient's quality of life, as well as for assessing the safety of the performed and planned restorative complex treatment of such patients. The objective: to analyze the dynamics of morphological changes of the mucous membrane in the gastrointestinal tract of patients with CP in comorbidity with etiotropically treated HCV under the influence of a protocol therapeutic complex with the additional inclusion of hepatotrophic drugs. Materials and methods. We analyzed the data of 55 patients with CP in comorbidity with HCV after etiotropic treatment of HCV, who were examined according to generally accepted algorithms and received a generally accepted complex of treatment according to the CP protocol. The patients were divided into two groups: the 1st group - 20 patients who received a generally accepted complex of treatment according to the protocol (PC) for 3 months; the 2nd group - 35 patients who received treatment according to the PC with the additional inclusion of a hepatotrophic agent for 3 months. In all the patients before and after treatment a morphological study of biopsies of the mucous membrane of the stomach and duodenum was performed. Results. In the course of the study, a significant improvement in the mucous membrane morphology of the GDZ of patients with a combination of CP and HCV was established after a course of treatment with the use of hepatoprotectors, namely: a decrease in lymphohistiocytic infiltration - by 3.97 times, restoration of the gland structure that did not undergo complete non-metaplastic atrophy - by 5,13 times, increased proliferation of the glandular epithelium as a sign of morphological restoration of the epithelium - 3.9 times, decrease in signs of epithelial dysplasia - 10.35 times, decrease in the number of erosions of the mucous membrane of the organs of the gastrointestinal tract - 2.6 times. Conclusions. The higher efficiency and safety of the complex treatment with the additional inclusion of a combination of hepatotrophic agents on the morphological condition of the mucous membrane of the organs of the gastroduodenal zone have been substantiated. [ABSTRACT FROM AUTHOR]

Background. Viral hepatitis C (HCV) is not only as a liver disease but also as a systemic (generalized) infection that affects other organs, in particular, the pancreas and gastroduodenal zone. The state of the gastrointestinal mucosa in combined course of chronic pancreatitis (CP) and chronic HCV is little studied, but extremely relevant, as it is important for the clinical course, the quality of life of patients, as well as for assessing the safety of the performed (etiotropic, etc.) and planned restorative comprehensive treatment of such patients. The purpose is to evaluate the morphological changes of the gastroduodenal mucosa of patients with chronic pancreatitis associated with chronic viral hepatitis C who were treated etiotropically. Materials and methods. Thirty patients with CP and 65 patients with CP in comorbidity with chronic HCV after etiotropic treatment of HCV were examined. Regardless of the HCV genotype, they received a course of treatment with sofosbuvir at a dose of 400 mg and velpatasvir 100 mg in the morning after meals for 3 months (some patients took daclatasvir at a dose of 60 mg also in the morning after meals for 3 months instead of velpatasvir). The period after diagnosed and treated HCV before the examination was on average (2.35 ± 0.61) years. All patients underwent a morphological study of gastric and duodenal biopsy samples obtained by esophagogastroscopy. The prepared samples were evaluated according to the international OLGA and OLGIM systems based on the evaluation of 5 gastric biopsies (1 from the corner of the stomach, 2 from the body, and 2 from the antrum) with a description of the main pathomorphological changes evaluated on a visual analog scale. Alcian yellow and toluidine blue were used to detect H.pylori. An own system for assessing the morphological state of the gastroduodenal mucosa was also proposed. Results. The detected structural changes indicate the presence of chronic atrophic gastritis with moderate dysplasia of the glandular epithelium. Stage of chronic gastritis according to the OLGA system was III. Stage of chronic gastritis according to the OLGIM system was III. Thus, the practically asymptomatic course of quite significant gastroduodenal changes in CP combined with chronic HCV requires additional therapeutic influence, as well as an assessment of comprehensive treatment based on the effect on the gastroduodenal mucosa. In case of changes in gastroduodenal mucosa in CP on the background of chronic HCV, in contrast to those with isolated CP, a significantly higher level of inflammatory infiltrate density (moderate (2+) vs. mild (1+)) is determined, which is accompanied by moderate neutrophilic infiltration (2+) vs. mild (1+) and mild lymphohistiocytic infiltration (1+) versus no such infiltration (0), the appearance of intestinal metaplasia (2+) and moderate non-metaplastic glandular atrophy (2+) versus the absence of metaplasia (0) and mild non-metaplastic glandular atrophy (1+), as well as zones of metaplastic atrophy (1+), which was manifested by the appearance of Paneth cells and goblet cells. In CP with chronic HCV, mucosa has atrophic changes. Metaplasia is manifested by a change in cellular phenotype: complete intestinal metaplasia type I–II is manifested by the appearance of Paneth cells and goblet cells; incomplete — by the presence of columnar epithelium and goblet cells; colonic metaplasia — by enlargement of the glands and the absence of Paneth cells. Conclusions. It was proved that the state of the gastric and duodenal mucosa in the group of patients with CP and chronic HCV was significantly severe than that in isolated CP: lymphohistiocytic infiltration of the mucous membrane was detected 2.68 times more often, non-metaplastic infiltration glandular atrophy (there was practically no glandular atrophy in the group of isolated CP) — 12.65 times more often, metaplastic atrophy (it was not detected in the group of CP) — 10.64 times more often, acute leukocyte infiltration — 2.31 times more often, dysplasia of the mucosal epithelium (with isolated CP, mild dysplasia was detected) — 7.30 times more often, erosion of the mucosal epithelium — 3.07 times more often, focal hyperplasia of the glands — 3.88 times more often, intestinal metaplasia — 12.89 times more often, which was practically absent in CP. In general, the total number of pathological signs of the mucous membrane in the group of CP with comorbid chronic HCV was found to be 2.76 times higher than that in isolated CP. [ABSTRACT FROM AUTHOR]

Purpose of the study: to develop, evaluate the effectiveness and applicability of an epidemiological model for the development of chronic viral hepatitis C, with the ability to predict the number of people who need to be tested for the presence of the virus.Materials and methods. In our study, we used official data for the Republic of Bashkortostan on the spread of chronic viral hepatitis C (annual dynamics of cases) in the period from 2005 to 2020, which were provided at our request by the Republican Clinical Infectious Diseases Hospital. Demographic indicators for births and deaths were taken from the annual statistical report of Bashkortostanstat. The study considered 2 mathematical models: 1) Model SIR considers three groups: susceptible (those who have not yet become infected), infected and dropouts (those who have recovered or died). 2) The STIRD model is the SIR model, improved by the author, which takes into account five population groups: susceptible (those who have not yet become infected), tested (those who have been in contact with the infected people and require a test to clarify the diagnosis), infected, dropouts (those who recovered) and deceased.Results: from 2015 to 2017, the model provided representative data on the forecast of the infected people, the error was about 1.5-4%, but after this period, starting from 2018, the error rate became critical and the model lost its representativeness. To explain this phenomenon, there are 2 reasons: the first is the easy availability of drugs for the treatment of chronic hepatitis C, the second is the need to use Markov models in the model, since the calculation does not take into account the dynamics of changes in the coefficients of the model. As a result of the coronavirus pandemic in 2020, the error was more than 166%, this is due to a decrease in contacts between people and, as a result, a sharp decrease in the incidence of chronic hepatitis C.Conclusion. The complete epidemiological STIRD model proposed by the author (taking into account the demographic change in the structure of the population) has shown itself well in medium-term forecasting up to three years. A significant advantage of this model specification compared to other epidemiological models is the ability to predict the number of diagnostic laboratory tests needed to detect a virus in humans. This is important, since the diagnosis and treatment of chronic hepatitis C is covered from compulsory medical insurance and regional budgets. Epidemiological modeling opens up great opportunities for developing scenarios for combating viral hepatitis C, especially with its chronic form, because, according to WHO, each country has the opportunity to completely get rid of this socially significant infection by 2030.

Introduction. Difficulties encountered in treating patients with chronic viral hepatitis C (CHC) are associated with the presence of concomitant liver pathology, namely, fatty degeneration which contributes to the progression of HCV infection. The above circumstances prompted the authorsled to thoroughly examine this category of patients for further development of a new pathogenetically directed course of treatment. Objective. The aim of the study was to investigate the clinical, biochemical, and instrumental features of the course of liver disease in CHC patients with concomitant non-alcoholic fatty liver disease (NAFLD). Materials and method. The study included 339 patients with chronic hepatitis C with concomitant NAFLD, and 175 patients with CHC. Methodology: anamnestic, anthropometric and clinical, general clinical, biochemical, serological, and molecular genetic (markers of hepatitis C virus, HCV RNA PCR (qualitative and quantitative determination, genotyping), enzyme-linked immunosorbent assay, ultrasonographic examination of digestive organs, and statistical methods were used. Results. The clinical, instrumental, and laboratory studies showed that CHC patients with concomitant NAFLD are characterized by various disorders -- a violation of the functional state of the liver, a violation of carbohydrate and lipid metabolism, an imbalance of the cytokine system, as well as the presence of histological and non-inflammatory activity in the liver. Conclusions. The presence of concomitant NAFLD in patients with CHC aggravates the clinical picture, manifesting itself in a significant lipid metabolism disorder that provokes the rapid formation of liver fibrosis. An additional complicating factor is the development of insulin resistance, leading to persistent morphological changes in the liver parenchyma. [ABSTRACT FROM AUTHOR]

Background. It was found that in 35–56 % of patients, hepatobiliary diseases are considered to be a factor causing the formation or exacerbation of chronic pancreatitis (CP) while reducing the share of pancreatitis of alcoholic etiology, as it was previously believed. However, the role of the alcohol factor and its consideration in the treatment strategy for CP and comorbidity with chronic viral hepatitis C (HCV) also needs to be clarified, because it is known that excessive alcohol consumption and smoking increases the risk of developing pancreatitis by 8–17 times. The purpose is to conduct a comparative analysis of parameters of the structural and functional state of the liver and pancreas in patients with chronic pancreatitis associated with chronic viral hepatitis C treated etiotropically, depending on the results of testing according to the international CAGE questionnaire. Materials and methods. We have examined 100 ambulatory patients with CP and concomitant HCV, treated etiotropically. All patients were examined according to generally accepted algorithms. To clarify the effect of alcohol on the formation of CP and the state of patients with treated HCV, latent craving for alcohol was verified using the international CAGE questionnaire. The study on the density of the liver parenchyma and the pancreas was carried out not only according to the ultrasound data in the B-mode, but also with the simultaneous shear wave elastography on the Ultima PA scanning ultrasound device with the further measurement of the median of the parameters in kilopascals. Determination of the presence and depth of exocrine pancreatic insufficiency was carried out by the content of fecal elastase-1 evaluated using the enzyme immunoassay method. Results. Screening-testing of patients with CP on the background of HCV treated etiotropically using the CAGE scale made it possible to state that 65.0 % of them had a latent craving for alcohol, and 21.0 % of this cohort were women, which needs to be taken into account in the management of such patients. It has been proven that in the group with CAGE ≥ 2.0, functional and structural changes in the liver and pancreas were significantly more severe (deepening of the exocrine pancreatic insufficiency with a decrease in fecal α-elastase by 13.01 %, an increase in the total index of the coprogram by 15.11 % and the total ultrasound indicator of the pancreatic structure by 28.06 %, and the total ultrasound indicator of the liver structure by 40.68 % (р < 0.05)) and corresponded to the average degree of severity of the process in the pancreas according to the criteria of the Marseille-Cambridge classification, and in the group with CAGE < 2.0 — only to a mild degree. Conclusions. The negative effect of the factor of increased alcohol use according to the CAGE was proven by increased density of pancreatic echotexture by 5.73 % (p < 0.05), and of the hepatic echotexture by 5.16 % (p < 0.05). According to the results of the correlation analysis on the dependence of the structural state of the liver and pancreas on the CAGE score, which were R = 0.713, p < 0.05, and R = 0.686, p < 0.05, respectively, there was found a strong direct dependence of the structural state of the liver and pancreas on the CAGE score, which proved an independent, reliably significant role of alcohol consumption for patients with a comorbid course of CP and HCV. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the phenotype of effector T lymphocytes in patients with chronic viral hepatitis C (CVHC) before and after of treatment with direct antiviral drugs depending on the genotype of the virus. 50 patients with CVHC without signs of liver cirrhosis were examined. The diagnosis was made on the basis of epidemiological and clinical laboratory data as recommended by the European Association for the Study of the Liver when specific serological markers of CHCV and RNA of hepatitis C virus (HCV) were detected (EASL, 2016). The determination of HCV RNA was carried out by the method of quantitative polymerase chain reaction in real time. The degree of liver fibrosis in patients with CVHC was assessed using ultrasound elastography. Patients were treated for 3 months with direct antiviral drugs according to the recommendations of the European Association for the Study of the Liver (2016). The control group included 46 practically healthy individuals with severe chronic diseases of various organs and systems excluded during a routine examination, no health complaints, having normal clinical and biochemical blood tests in the absence of markers for viral hepatitis B and C, antibodies to opisthorchis and denying history of alcohol abuse. The study of the subpopulation composition of helper and cytotoxic T lymphocytes was carried out by direct immunofluorescence of whole peripheral blood. We obtained a 100% sustained virological response in patients with 1, 2 and genotypes of CHCV without signs of liver cirrhosis when using therapy with Sofosbuvir (400 mg) and Daclatasvir (60 mg) for 12 weeks. It was found that in CVHC patients were found characteristic features in the phenotypic composition of effector T lymphocytes before and after treatment with direct antiviral drugs in depending on the genotype of HCV. Patients with HCV genotypes 1 and 3 had an increase in the content of terminal differentiated effector (TEMRA) T helpers and effector memory (EM). Only patients with HCV genotype 2 had a decrease in the level of EM T-helper cells in the blood. A decrease in the relative number of T helpers of central memory (СM) was independent of the HCV genotype. The level of effector subpopulations of cytotoxic T lymphocytes in patients with CVHC was consistent with or exceeded control levels in depending on the genotype of HCV. The level of all investigated subpopulations of effector cytotoxic T lymphocytes in patients with HCV genotype 1 was equal to the control values. The number of naïve cytotoxic T cells and CM in peripheral blood in patients with HCV genotype 2 was increased. The content of naïve cytotoxic T lymphocytes, CM and TEMRA in patients with genotype 3 HCV in the blood was increased. The highest viral load was detected in patients with CVHC with genotype 1 HCV. Liver fibrosis was most pronounced in patients with CVHC infection with HCV genotypes 2 and 3. After 3 months of treatment with direct antiviral drugs the patients with CVHC had a reduced content of CM T helpers regardless of the HCV genotype. In addition, patients with HCV genotypes 1 and 3 had a decrease in the number of naïve T helpers and patients with HCV genotypes 2 and 3 had a normalization of the content of naïve cytotoxic T lymphocytes.

Background. The spread of chronic viral hepatitis C (CVHC) among the population entails significant costs for society, both direct, associated with the treatment of such patients, and indirect, associated with the shortfall in fiscal payments to the budget, due to the disability of this category of patients. Therefore, an important task remains to assess the global economic burden of the disease, taking into account the pathological conditions of the human body associated with it.Objective: to systematize studies of published sources devoted to assessing the global economic burden of chronic viral hepatitis C.Material and methods. A feature of the proposed review design is paying attention not only to the objects of assessment under study, but also to the instrumental (including mathematical) means of scenario assessment of the global burden. The study analyzed 29 sources published between 2014 and 2020 and dedicated to assessing and forecasting the global economic burden of CVHC both in individual countries and continents as a whole, and in individual regions of countries. The main criterion for the selection of studies was the availability of an estimate of the global burden of CVHC, taking into account the use of direct antiviral drugs for the treatment of hepatitis C. The search was conducted in PubMed/MEDLINE and eLibrary databases, and in the ResearchGate network.Results. Of the 29 analyzed sources, 40% of the works consider the burden for CVHC only of certain genotypes; in the overwhelming number of articles (80%), when assessing the burden, the distribution of patients by the degree of liver fibrosis is taken into account. In 50% of the studies reviewed, quality of life adjustment tools (QALY or DALY) were used to estimate the global economic burden. A third of the publications took into account both the direct costs of treating CVHC and indirect costs, including those associated with a shortfall in the contribution to the gross national product due to temporary or permanent disability of this category of patients.Conclusion. The analysis showed that interest in assessing the global burden of CVHC began to appear in recent years, when expensive directacting antivirals for the treatment appeared. This is explained by the emergence of a question about the cost of implementing a scenario in which by a certain year it will be possible to completely exclude the spread of the disease. The results of this work may be useful in conducting such studies, including the determining of their design and the use of modern mathematical modeling tools.

The significant spread of chronic viral hepatitis in Ukraine and the whole world, an increase in the incidence of medical personnel, and the lack of wariness of the population regarding the diseases of this group make it necessary to have a statistical analysis of the etiology, diagnosis, treatment, and prevention of viral hepatitis among different population groups.Aim. To study and analyze the awareness about viral hepatitis B (HBV) and C (HCV) of patients who undergo treatment in various departments (infectious, surgical, therapeutic) and the students who didn't take the course of infectious diseases.Materials and methods. A questionnaire was developed to establish the level of awareness among patients with viral hepatitis. The study was conducted through a sociological survey (full-time, one-time, individual) with the preservation of confidentiality conditions. The study was conducted in the infectious department of Sumy Regional Infectious Diseases Clinical Hospital named after ZY Krasovitsky, Surgical Department of Sumy City Clinical Hospital №5, therapeutic department of Sumy Regional Clinical Hospital of the 4th year of Sumy State University Medical Institute in 2019. In total, 147 people took part in the survey: 20 were in treatment at the therapeutic ward, 20 - in the surgical ward, 20 - in the infectious diseases department, and 20 - 4th-year students.Conclusions. Viral hepatitis is currently one of the most pressing health problems. It is used for the sociological survey we developed to determine the level of knowledge of the population about the causative agent of viral hepatitis, transmission, prevention (not specific and specific), clinical features, laboratory methods of diagnosis, and treatment.Among all the surveyed results, recipients gave most of the correct answers to questions about the causative agent of viral hepatitis and transmission routes. The worst known are patients in the surgical wards about the presence of an effective hepatitis B vaccine (20.00%); patients of infectious and therapeutic wards (20.00% each) and 4th-year students (25.00%) - about the presence of effective hepatitis C therapy; (95.00%) and a reference group of physicians (100.00%) on the etiology of viral hepatitis. Patients in surgical wards (84.30%) answered the most frequently asked questions about the ways of transmission of viral hepatitis.

According to WHO, about 150-200 million people are currently infected with the HCV virus worldwide. Recently, in the professional literature, the number of publications on the role of vitamin D in patients with viral hepatitis C has increased as vitamin D metabolism occurs with the participation of the liver and its deficiency is associated with an increased risk of infectious diseases. The aim of this study was to investigate the effect of seasonal factor on vitamin D (25 hydroxycalciferol) levels in patients with chronic viral hepatitis C and healthy subjects. The study involved 100 patients in the registry of patients with chronic viral hepatitis in the Dnipropetrovsk region. The prevalence and deficiency of vitamin D in patients with chronic viral hepatitis C and conditionally healthy subjects at different times of the year were determined, which showed the presence or absence of a seasonal effect on serum 25(OH)D level. Patients were divided into two groups, depending on the time of the year (autumn-winter and spring-summer), in which the level of 25 (OH) D was determined. The serum was metabolised by vitamin D, which is synthesized by the liver – 25 hydroxycalciferol (25 (OH) D), an indicator of the supply of vitamin D to the human body. Vitamin D levels were evaluated according to the M.F. Holick classification. According to the level of vitamin D patients were divided into 3 groups (patients with normal level, insufficient (suboptimal) level and vitamin D deficiency). The results of the study showed no effect of seasonal factor on the level of 25 (OH) D in the serum of patients with chronic viral hepatitis C. Vitamin D levels are controlled by the time of the year: in spring and summer this indicator is normal, in autumn and winter – seasonal decrease in vitamin D.

Necrotizing soft tissue infection (NSTI) is a severe surgical infection which can result in sepsis and septic shock when generalized.The aim of the study was to determine the frequency of thrombocytopenia in patients with generalized NSTI, the factors promoting its development, and its association with septic shock.Materials and Methods. We examined 129 patients with NSTI treated between 09.2015 and 12.2019 at St. George Hospital in St. Petersburg, Russia. Surgical treatment, hematological and biochemical examinations, and bacteriological analysis of blood and wound discharge were performed in each patient. The studied group included 22 patients with systemic inflammatory reaction syndrome, 63 patients with sepsis, and 44 patients with septic shock.Results. We found a decrease in platelet count in NSTI patients with septic shock as early as on the first day of the disease and its further decrease within the next 3 days, with the mean platelet volume (MPV) increasing during the same period and significantly exceeding that in patients with sepsis and systemic inflammatory response syndrome. In NSTI patients with thrombocytopenia on admission, we found a significant correlation between the platelet count and the percentage of segmented neutrophils (r=0.349; P

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The authors present the study of the level of expression of miR-196a in 74 patients with chronic viral hepatitis C with the 1st genotype of HCV, based on previous experience in patients with antiviral therapy regimens containing interferon. The patients were divided into two groups, depending on the previous experience of antiviral therapy with circuits containing interferon – 21 patients who failed after antiviral therapy regimens containing interferon (group 1) and the comparison group (group 2) – 53 naive patients. To study the level of expression of miR-196a (miR-196a), a two-stage study according to the manufacturer's protocol was used. First, total RNA was isolated from the plasma by the method of phenol-chloroform extraction. Futher reverse transcription was performed using a kit for reverse transcription of miR TaqMan® (Applied Biosystems, USA), specific loop primers to achieve mature miRNA, snRNA U6 (as an endogenous control gene), and 10 ng of total RNA. Real-time quantitative PCR was performed using TaqMan® miRNA analysis. In order to optimize the prediction of response to antiviral therapy and the use of optimal treatment regimens for problem patients with treatment failure regimens containing interferon, analysis using ROC curves was used. The average level of expression of miR-196a in patients with chronic hepatitis C was evaluated. In the 1st group of patients it was 0.011 (IQR: 0.002; 0.310) and in the comparison group – 0.346 (IQR: 0.054; 1.239) at p=0.012 by U criterion. The conducted ROC analysis showed that the studied miR-196a could differentiate patients with chronic viral hepatitis C with HCV genotype 1, depending on previous experience of antiviral therapy, namely, patients with treatment failure regimens containing interferons and naive. AUC=0.688 (95% CI 0.570-0.791; p=0.017), J=0.40, Se=57.14%, Sp=83.02%. It gives additional opportunities for correction of therapeutic tactics. Therefore, the level of expression of miR-196a (

The paper analyzes modern views on the etiology, epidemiology, pathogenesis, methods of treating patients with chronic viral hepatitis C with concomitant non-alcoholic fatty liver disease (NAFLD), discusses the possibility of using "dry" carbon dioxide baths (DCDB) in this category of patients. Our research was conducted to study the effectiveness of the integrated use of antiviral therapy (AVT) and DCDB procedures in patients with chronic hepatitis C with concomitant NAFLD. The authors of the study were the first to suggest using of DCDB in this category of patients. Based on the results obtained, for the first time, ideas about the specificity of the DCDBʹs effect on the clinical course of the underlying and concomitant diseases, on the functional state of the liver, the dynamics of lipid metabolism, and ultrasonographic parameters of the liver were detailed. It is concluded that DCDB can be successfully used in the complex treatment of patients with chronic hepatitis C with concomitant NAFLD.

A total of 287 patients were treated with various antiviral therapy options: group I – basic (pathogenetic and symptomatic) therapy, group II – pegylated interferon in combination with ribavirin, group III – pegylated interferon with ribavirin and sofosbuvir, group IV – direct-acting antivirals. Patients with chronic viral hepatitis C (CVHC) before the start of treatment showed a decrease in platelet counts, segmented neutrophils and an increase in level of lymphocytes, bilirubin content, alanine aminotransferase activity, aspartate, transferrinase (practice), with a comparison group (practically virus-free patients) The investigated integrative indicators suggest changes in the immune system of patients, in particular the prevalence of cellular immunity over the humoral link and the predominance of the autoimmune component. Patients with dual and triple PVT regimens had more pronounced changes compared to patients receiving DAAs.

The article reviews the literature on the effectiveness of antiviral therapy in chronic viral hepatitis C. Data presented by World Health Organization recommendations for the algorithm for the diagnosis, treatment and monitoring of viral hepatitis C.

Introduction: The use of modern drugs with direct antiviral effect allows achieving a stable virologic response (SVR) in patients with chronic hepatitis C (CHC). However, in most cases, after the elimination of HCV infection, the progression of fibrosis continues with the development of its terminal stages and adverse outcomes for patients. The presence of non-alcoholic fatty liver disease (NAFLD) in these patients significantly increases the rate of progression of fibrosis and its complications, even after reaching SVR. Therefore, the search and development of new non-drug treatment technologies for this category of patients is relevant. Aim: to study the effectiveness of mineral water intake (with a high content of bicarbonates, sodium, potassium, and silicon compounds) in the new mode of use in the complex treatment of patients with chronic hepatitis C with concomitant NAFLD. Methods: anamnestic, clinical, general clinical, biochemical (indicators of lipid metabolism, HOMA index), serological (markers of viral hepatitis C, HCV RNA PCR, qualitative and quantitative determination, genotyping), ultrasonographic studies of the digestive system and statistical methods. Results: Patients with chronic hepatitis C (genotype 1b in the phase of replication, minimal and moderate activity) with concomitant NAFLD, which had been divided into two groups, were examined. Patients of group I (control group) received a standard complex of treatment (diet therapy that corresponded to the Mediterranean diet, dosed exercise regimen, antiviral therapy - sofosbuvir (400 mg) and ledipasvir (90 mg) - 3 months). Patients of group II (the main group) additionally received an internal course intake of mineral water (MW) according to our methodology: 3 ml per kg of patient’s body weight 30-40-60 min before meals, depending on the acidity in the stomach, and the same dose after food intake, three times a day (course - 2 months, a break - 2 months, a second course - 2 months). Evaluation of the effectiveness of treatment was carried out after six months from the start of treatment. Conclusion: The results prove the feasibility and effectiveness of using MW in a doubled dosage regimen in the complex treatment of patients with chronic hepatitis C with chronic concomitant NAFLD, which was determined by improving lipid metabolism, reducing signs of insulin resistance, improving ultrasonographic signs and preventing the development of fibrotic changes in the liver.

One of the urgent problems of modern hepatology remains the treatment of patients with chronic viral hepatitis C, which is associated with an increase in the incidence and development of complications - cirrhosis of the liver and hepatocellular carcinoma. The presence of non-alcoholic fatty liver disease in patients accelerates the progression rate of HCV infection and reduces the effectiveness and tolerability of antiviral therapy. The above circumstances initiated us to the search for new non-drug technologies for the treatment of this category of patients. The work aimed to evaluate the effectiveness of the integrated use of standard antiviral therapy, drinking silicon low-mineralized sodium bicarbonate mineral water, and EHF-therapy in patients with chronic viral hepatitis C with concomitant non-alcoholic fatty liver disease. We used the following methods: anamnestic, general clinical, biochemical, serological, immunological, Ultrasonographic examination of the digestive organs. We examined 42 patients who were divided into two groups. The control group (22 people) received the basic treatment complex, which included dietary nutrition, standard antiviral therapy for 12 months, and an internal intake of mineral water during the first month of treatment. The main group (20 people), in addition to the basic complex of treatment, additionally received EHF-therapy procedures for three months. Evaluation of the effectiveness of treatment was carried out after 1 and 3 months from the start of treatment. The treatment was accompanied by the positive dynamics of most signs of the disease in both groups, with a predominance of EHF-therapy. In patients of main group, the disappearance of complications of antiviral therapy was established - the absence of cytopenic syndrome, normalization of immunological status, stimulation of interferonogenesis, restoration of equilibrium in the lipid peroxidation system and antioxidant system. These positive results made it possible to complete the course of therapy for all patients and obtain a virological response in 50% of patients.

The aim. is to develop a method, for predicting the development of lipid, distress syndrome in patients with a sustained, response to antiviral therapy of chronic viral hepatitis C on the basis of clinical and laboratory data.Materials and. methods. The outcomes of lipid, distress syndrome were studied in 235 patients with a sustained vi-rological response to antiviral therapy of chronic hepatitis C during the follow-up period, from 1 to 10 years.Results. On the basis of discriminant analysis of the data of complex examination of 135 patients, a discriminant model of predicting the development of lipid distress syndrome in patients with a sustained response to antiviral therapy of chronic hepatitis C. On the basis of the data of the survey of other 100 patients, cross-checking the accuracy of the prediction. was carried out.Conclusion. Developed, diskriminantnaja model allows by identifying 5 of biochemical and. immunological parameters of blood (low-density lipoproteins cholesterol, homocysteine, interleukin. 4 and. 10, TNF) to predict the development of lipid distress syndrome in patients with sustained response to antiviral therapy for chronic hepatitis С. The sensitivity, specificity, predictive value of positive and. negative results of forecasting and precision index developed forecasting model of Fisher discriminant lipid, distress syndrome equal 100%. The proposed, method, should, be used, in clinical practice to predict development of lipid, distress syndrome in patients with sustained, response to antiviral therapy for chronic hepatitis C.

Background. Today, the programmed hemodialysis belongs to the clinical medicine area where patients are at a constant risk of viral hepatitis infection. This is associated with surgical interventions on the vessels, fairly frequent transfusions of blood components, and regular hemodialysis procedures. But in recent years, the ratio of reported cases of viral hepatitis B and C in patients on programmed hemodialysis has changed significantly. With an abrupt increase in the incidence of viral hepatitis C, there is a decrease in the number of registered viral hepatitis B cases.The aim. To study the clinical, epidemiological and pathogenetic features of viral hepatitis C in hemodialysis units.Material and methods. A multicenter study was conducted that enrolled the patients from the Programmed Hemodialysis Units in Tashkent and the regional departments of the Republic of Uzbekistan. The study involved 395 patients on programmed hemodialysis for 7.5 ± 0.7 years. The age of patients was 43.5 ± 0.91 years. The diagnosis of chronic viral hepatitis C was made on the basis of medical history, clinical and laboratory data, and detection of anti-HCV IgG and RNA-HCV in blood.Results. When analyzing the clinical examination and laboratory test results of 395 patients, the parenteral viral infection markers were detected in 181 patients (45.8%). The analysis of the overall incidence of viral hepatitis showed that chronic viral hepatitis C had the highest rates and was found in 125 patients (31.6%). The analysis of the chronic viral hepatitis C course in the presence of the end-stage chronic renal disease showed that in 11 (34%) of 32 patients of the Main group the disease proceeded as a fulminant form of chronic renal-hepatic failure with the development of adverse outcomes. Twenty seven patients (84%) in this group developed progressive anemia. In 16 patients (50%), persistent polyserositis developed in the form of hydrothorax, ascites, and pericarditis, which reflected the aggravating effect of chronic viral hepatitis C on the course of chronic renal disease.Conclusions. In Hemodialysis Units, both in the city of Tashkent, and in the regional departments of the Republic of Uzbekistan, the incidence of chronic viral hepatitis C prevails, having the form of a pathological process with a minimally low activity. Chronic viral hepatitis C has an aggravating effect on the course of the underlying disease with the development of adverse outcomes.

Objective To investigate the prevalence of and risk factors for type 2 diabetes mellitus in patients with chronic viral hepatitis C. Methods A total of 294 patients with chronic hepatitis C in Yunnan First People's Hospital from January 2018 to May 2020 were divided into two groups: 70 patients with diabetes and 224 patients without diabetes. After deletion of incomplete data, 56 patients with hepatitis C complicated with diabetes and 59 patients without diabetes were selected, then another 52 patients with type 2 diabetes mellitus who were treated in Endocrinology and Metabolism Department of Yunnan First People's Hospital in October 2020 were randomly selected for the study. General clinical data (gender, age, Place of residence, alcohol consumption) and laboratory tests (HCV RNA, hepatitis C antibody, LDH, AST, ALP, GGT, TBIL, DBIL, TBA, TP, ALB, GLB, BUN, CR, UA, TC, TG, HDL-C, LDL, blood sugar) were collected, and SPSS26.0 statistical software was used to establish a database and analyze whether there are statistical differences in blood biochemical indexes among the three groups of patients, and use disordered multivariate logistic regression to analyze risk factors. Results The detection rate of type 2 diabetes mellitus in patients with Chronic hepatitis C was 23.8%. There were significant differences in sex, age, region, alcohol consumption, UA, GLB, LDL-C, TC, LDH, GLB, AST, ALP, GGT, TBiL, DBiL, TBA and TG among the three groups (P < 0.05), but there were no significant differences in TP, HDL-C, BUN and CR (P > 0.05) . Disordered multivariate Logistic regression analysis showed that age and TBA were the risk factors of type 2 diabetes in patients with chronic hepatitis C (P < 0.05). Conclusion Hepatitis C virus infection can aggravate liver injury, and elderly patients with hepatitis C with high TBA level are more likely to develop type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aim: To investigate the parameters of the functional state of the pancreas in chronic pancreatitis in the background of chronic viral hepatitis C, as well as their dynamics under the influence of complex therapy with the inclusion of complex bioregulatory drugs. Materials and Methods: 106 patients were examined: patients with CP in remission, patients with CP in remission in combination with HCV in remission, and after antiviral therapy. Patients with CP and concomitant HCV were divided into two groups according to correction programs. Group I (36 patients) received only conventional treatment: antispasmodics and/or prokinetics, enzyme preparations, proton pump inhibitors, hepatoprotectors in the mode “on-demand”. Group II (36 patients), in addition to conventional treatment, received additional complex bioregulatory drugs. Results: After treatment, there was an improvement in coprogram results and an increase in fecal elastase-1 levels. Positive dynamics was observed in both groups, but in patients of group I it was statistically insignificant (p>0.05), while in the group of patients who additionally received complex of bioregulatory drugs, the changes were more pronounced: in group II the level of fecal elastase-1 increased by 52.79% (p<0.05). Conclusions: This indicates a statistically significant effect of treatment using a complex bioregulatory corrector of exocrine insufficiency (Momordica Compositum: 1 ampoule 2.2 ml intramuscularly 3 times a week №10) and a complex bioregulatory hepatotropic drug (Hepeel: 1 tab. sublingually 3 times a day 15-20 minutes before meals or 1 hour after meals for 1 month). [ABSTRACT FROM AUTHOR]

The second-generation of direct-acting antiviral agents are the current treatment for chronic viral hepatitis C infection. To evaluate the regression of liver fibrosis in patients receiving this therapy, liver biopsy remains the most accurate method, but the invasiveness of this procedure is its major drawback. Different non-invasive tests have been used to study changes in the stage of liver fibrosis in patients with chronic viral hepatitis treated with the second-generation of direct-acting antiviral agents: liver stiffness measurements (with transient elastography or acoustic radiation force impulse elastography) or different scores that use serum markers to calculate a fibrosis score. We prepared a literature review of the available data regarding the long-term evolution of liver fibrosis after the treatment with direct-acting antiviral agents for chronic viral hepatitis C.

Aim. To study the features of lipid peroxidation of biological membranes and accumulation of toxic metabolites in the body of patients with psoriasis, depending on the presence of concomitant chronic viral hepatitis C.Materials and methods. In the survey, participated 56 patients with a vulgar form of psoriasis who received in-patient treatment at the Nalchik skin clinic in 2016–2017, divided into 2 groups, depending on the presence of concomitant chronic viral hepatitis C. In patients, the content of malonic dialdehyde in blood was determined as an indicator of the state of the prooxidant system, ceruloplasmin and erythrocyte catalase, as indicators of antioxidant protection, and also for the evaluation of the Intoxication Syndrome; the level of substances of low and medium molecular mass and oligopeptides in the biological environments of the organism in different periods of the disease.Results. It was found that the presence of concomitant chronic viral hepatitis C in patients with psoriasis was characterized by a more pronounced increase in the concentration of lipid peroxidation products than in the group of patients with hepatitis without psoriasis, accompanied by a decrease in the activity of antioxidant enzymes in the blood plasma and an increase in the activity of catalase in erythrocytes. Simultaneously, the presence of chronic hepatitis C led to a significantly higher content in the body fluids of patients with low and medium molecular weight substances and oligopeptides.

According to WHO, about 150- 200 million people are currently infected with the HCV virus worldwide. Recently, in the professional literature, the number of publications on the role of vitamin D in patients with viral hepatitis C has increased as vitamin D metabolism occurs with the participation of the liver and its deficiency is associated with an increased risk of infectious diseases. The aim of this study was to investigate the effect of seasonal factor on vitamin D (25 hydroxycalciferol) levels in patients with chronic viral hepatitis C and healthy subjects. The study involved 100 patients in the registry of patients with chronic viral hepatitis in the Dnipropetrovsk region. The prevalence and deficiency of vitamin D in patients with chronic viral hepatitis C and conditionally healthy subjects at different times of the year were determined, which showed the presence or absence of a seasonal effect on serum 25(OH)D level. Patients were divided into two groups, depending on the time of the year (autumn-winter and spring-summer), in which the level of 25 (OH) D was determined. The serum was metabolised by vitamin D, which is synthesized by the liver – 25 hydroxycalciferol (25 (OH) D), an indicator of the supply of vitamin D to the human body. Vitamin D levels were evaluated according to the M.F. Holick classification. According to the level of vitamin D patients were divided into 3 groups (patients with normal level, insufficient (suboptimal) level and vitamin D deficiency). The results of the study showed no effect of seasonal factor on the level of 25 (OH) D in the serum of patients with chronic viral hepatitis C. Vitamin D levels are controlled by the time of the year: in spring and summer this indicator is normal, in autumn and winter – seasonal decrease in vitamin D. [ABSTRACT FROM AUTHOR]

Introduction. One of the most severe diffuse liver diseases is chronic viral hepatitis C (CHC) combined with non-alcoholic fatty liver disease (NAFLD). After completing the treatment of CHC with drugs of direct antiviral action, there remains a high risk of further progression of liver fibrosis associated with the presence of comorbid pathology - NAFLD in patients. The above circumstances initiated us to search for new non-drug technologies to treat this category of patients. Purpose of the work: to study the effectiveness of use bentonite suspension in rats with a model of NAFLD and to substantiate the practicality of using bentonite in the complex treatment of CHC patients with concomitant NAFLD. Methods: experimental, anamnestic and clinical, general clinical, biochemical, determination of the HOMA index, leptin and adiponectin levels, ultrasonographic studies of the digestive system, bacteriological examination of feces, statistical methods.Results: According to microscopic examination, bentonite application in animals with the NAFLC model leads to a decrease in liver steatosis, restoration of bile formation and bile secretion, and protein-synthesizing liver function. In the blood, there was a positive dynamics to the restoration of energy-dependent transmembrane ion transport according to the activity of Na+/K+ -ATPase and Mg2+/Ca2+ -ATPase (in the liver tissue) and the balance of the antioxidant system (to restrain malondialdehyde and catalase activity). We examined 40 patients with CHC with concomitant NAFLD, who completed the course of antiviral therapy (AVT) and were divided into two groups. 1 (control) group (20 people) received a basic treatment complex (diet therapy, which corresponded to the Mediterranean diet, a regimen of dosed physical exertion, patients of 2 groups (20 people, the main group) additionally received a preparation based on bentonite clay inside - 10 days (1 dose three times a day) Evaluation of the effectiveness of treatment was carried out one month after the start of treatment. Conclusion: The treatment carried out in both groups was accompanied by positive dynamics in most of the diseaseʹs symptoms. But a significant advantage was observed in the second group, where the normalization of cholestatic and dyslipidemic syndromes was established, that is, the effect on the pathogenetic links of the progression of NAFLD was proved. The results obtained confirm the practicality of using the drug with bentonite in the complex treatment of CHC patients with concomitant NAFLD. [ABSTRACT FROM AUTHOR]

The authors present the experience of antiviral treatment of patients with chronic viral hepatitis C (HVHC) within the framework of the State Target Social Program for the Prevention, Diagnosis and Treatment of Viral Hepatitis until 2016 and the local program "Population Health of Dnipropetrovsk Region for 2015-2019". The authors reviewed the treatment regimens that can be used in patients according to the latest recommendations of WHO and international organizations on the study of the liver (EASL, APASL and AASLD). The authors discussed the problematic issues of the effectiveness of treatment regimens containing interferon and ribavirin, as well as interferon-free regimens of therapy. At the first stage of the work, the authors noted the coverage of with antiviral therapy of HVHC patients in the Dnipropetrovsk region, taking into account the patients followed up the Unified electronic registry of patients of adult age with chronic viral hepatitis B, C and B + C. 3875 patients are included in the register, 3334 have HVHC, of them – 2795 patients with viremia. Antiviral therapy was received by 1038 patients with chronic viral hepatitis, including those with HVHC – 912 patients. In 2017, 725 people with HVHC completed antiviral therapy, the coverage of treatment was 21.75% of the total need, based on the number of patients in the Registry. As a result of treatment, 22 patients with the 1st genotype of HCV, had failed therapy with interferon-containing regimens. However, in a detailed analysis, the authors found that in one case there was a reinfection with another HCV genotype. Relapse was determined in 14 (63%) patients, partial virological response in 3 (14%) patients and non-response in 4 (23%) patients. At the second stage of the work, the re-treatment regimen was evaluated in patients with treatment failure after the use of PEG-IFN regimens using interferon-free regimens containing direct-acting antiviral drugs (DAA) for 12 weeks in 21 patients with an average age of 42.4±2.89 years, with the 1st HCV genotype, with an average disease duration of 6.52±1.05 years. There were 14 men with a mean age of 39.67±4.16 years and 9 women with a mean age of 46.22±4.01 years. The level of fibrosis: F1 – 8 people, F2 – 7, F3 – 3 and F4 – 3. 3D treatment regimen was used for retreatment including the following: Ombitasvir / Paritaprevir / Ritonavir + Dasabuvir + Ribavirin (3D+RBV) in 16 patients, moreover, 3 of them had compensated liver cirrhosis. 5 patients with HCV genotype 1 without the presence of liver cirrhosis were given the following scheme: Ledipasvir + Sofosbuvir + Ribavirin (SOF+LDV+RBV). All patients had a sustained virological response (SVR-24) and the effectiveness of the antiviral therapy was rated as 100%. Also two clinical cases of treatment of HVHC in patients with antiviral therapy failure are presented. For further implementation of the WHO strategy for the elimination of viral hepatitis, it is necessary to continue the work on the formation of the Registry of patients with chronic viral hepatitis in order to improve the provision of care to patients in this category. Further study of the issue of personalization of antiviral therapy and minimization of risks that adversely affect its results are required.

Chronic viral hepatitis C (CHC) remains a significant medical and social problem worldwide and is a leader in the structure of etiological factors in the development of diffuse liver diseases (NAFLD). The presence of NAFLD in patients with chronic hepatitis C accelerates the progression rate of HCV infection and reduces the effectiveness and tolerability of antiviral therapy. The above circumstances initiated us to the search for new non-drug technologies for the treatment of this category of patients. The purpose of these work is evaluate the effectiveness of the integrated use of standard antiviral therapy, the drinking of low-mineralized silicon sodium bicarbonate mineral water (MW), and vibroacoustic therapy (VT) in patients with chronic hepatitis C with concomitant NAFLD. Research methods: anamnestic and clinical, general clinical, biochemical, serological (markers of viral hepatitis C, HCV RNA PCR (qualitative and quantitative determination, genotyping), quantitative determination of total endogenous α-interferon in the blood serum, ultrasonographic tudies of the digestive system, statistical methods. Fifty patients with chronic hepatitis C (genotype 1b in the phase of replication, minimal and moderate activity) with concomitant NAFLD were examined. Patients were divided into two groups. Patients of the I (control) group (25 people) received the basic treatment complex, which included dietary nutrition (diet No. 5), standard antiviral therapy (AVT) (interferon alfa-2 b and ribavirin) for 12 months and internal intake of MW for the first month of reatment. Patients of group II (25 people), in addition to the basic complex of treatment, additionally received VT procedures, the course of which was six months. Evaluation of the effectiveness of treatment was carried out after 1, 3, 6, and 12 months from the start of treatment. The treatment in both groups was accompanied by the positive dynamics of most of the signs of the disease; however, a significant advantage of using VT was found. In patients of group II, the side effects of AVT - influenzalike and cytopenic syndromes - disappeared, nterferonogenesis was stimulated, which made it possible to complete the AVT course in 92.00% of patients and obtain a virological response in 56.00% of patients. In other cases, reduce the virological load by no less than 2 log [ABSTRACT FROM AUTHOR]

The authors present the study of the level of expression of miR-196a in 74 patients with chronic viral hepatitis C with the 1st genotype of HCV, based on previous experience in patients with antiviral therapy regimens containing interferon. The patients were divided into two groups, depending on the previous experience of antiviral therapy with circuits containing interferon – 21 patients who failed after antiviral therapy regimens containing interferon (group 1) and the comparison group (group 2) – 53 naive patients. To study the level of expression of miR-196a (miR-196a), a two-stage study according to the manufacturer's protocol was used. First, total RNA was isolated from the plasma by the method of phenol-chloroform extraction. Futher reverse transcription was performed using a kit for reverse transcription of miR TaqMan® (Applied Biosystems, USA), specific loop primers to achieve mature miRNA, snRNA U6 (as an endogenous control gene), and 10 ng of total RNA. Real-time quantitative PCR was performed using TaqMan® miRNA analysis. In order to optimize the prediction of response to antiviral therapy and the use of optimal treatment regimens for problem patients with treatment failure regimens containing interferon, analysis using ROC curves was used. The average level of expression of miR-196a in patients with chronic hepatitis C was evaluated. In the 1st group of patients it was 0.011 (IQR: 0.002; 0.310) and in the comparison group – 0.346 (IQR: 0.054; 1.239) at p=0.012 by U criterion. The conducted ROC analysis showed that the studied miR-196a could differentiate patients with chronic viral hepatitis C with HCV genotype 1, depending on previous experience of antiviral therapy, namely, patients with treatment failure regimens containing interferons and naive. AUC=0.688 (95% CI 0.570-0.791; p=0.017), J=0.40, Se=57.14%, Sp=83.02%. It gives additional opportunities for correction of therapeutic tactics. Therefore, the level of expression of miR-196a (<-1,75) may be an additional biomarker in the pathogenesis of HCV-infection, which can then be used in the monitoring and treatment of patients. Low expression of miR-196a may be the basis for prescribing more effective direct-acting antiviral therapy to patients and will allow personalizing therapeutic tactics in patients with chronic viral hepatitis C. [ABSTRACT FROM AUTHOR]

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The article presents the adap­tation data of the quality of life questionnaire (QOL) in patients with chronic viral hepatitis C (CVHC). Ball score of QOL of patients with CVHC was 5.09±1.04, 2nd group (with co-infection with HIV / HCV) - 4.60±1.13, control group - 5.92±0.52 (p

Hepatocellular carcinoma (HCC) is currently the most severe form of liver disease consisting of malignant processes following fibrotic and cirrhotic damage. Despite there are several validated scores for assessing the overall risk to develop HCC in patients diagnosed with chronic liver diseases, most of these are designed for patients with viral hepatitis B and C and subsequently rely on specific measurements, such as viral load or viral profiling. PAGE-B is commonly used to predict HCC risk in patients with viral hepatitis B. In this context, this study aimed to evaluate the applicability of PAGE-B in different liver diseases predisposing to HCC. On a series of 104 consecutive patients, PAGE-B was calculated according to standard guidelines. Based on the collected data, the applicability of PAGE-B was evaluated in several liver pathologies predisposing to HCC, such as alcoholic liver disease, chronic viral hepatitis C, and non-alcoholic fatty liver disease. The mean age of the patients was 67,65 ± 1,15 years, while the sex distribution was 57,28 % males to 42,72 % females. The selected cohort consisted of 11 patients with alcoholic liver disease (10,57 %), 54 patients with chronic viral hepatitis C (51,92 %), and 39 patients with non-alcoholic fatty liver disease (37,5 %). We found that the patients with alcoholic liver disease patients scored highest for PAGE-B (20,09 ± 0,45), while non-alcoholic fatty liver disease patients score lowest (17,89 ± 0,47), significantly different from one another (p = 0,021). In conclusion, our results suggested that PAGE-B could be useful in evaluating HCC risk in chronic liver diseases, but further studies are needed to find a suitable scoring system to predict the overall risk to develop HCC in patients that are diagnosed with nonalcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

Detecting new units of pathogenesis in the liver fibrosis due to alcoholism, chronic viral Hepatitis B and C, non-alcoholic fatty liver disease (NAFLD), autoimmune, parasitic and metabolic diseases and other, reveals perspective for new non-invasive serum biomarkers. In fibrosis, from the wide variety of markers enzymes, proteins and cytokines are mainly used. While direct biomarkers reflect the stage of fibrosis and fibrinogenesis, indirect markers allow assessment of the general liver functions. The combination of direct and indirect markers increases the diagnostic reliability and therefore these panels and indices are investigated quite intensively in recent years in order to decrease the number of liver biopsies without completely replace it, which is still regarded as the reference method.

Introduction in practice of therapeutic establishments in the RF of antiviral therapy of chronic viral hepatitis in the form of interferon-free schemes led to considerable increase of the frequency of the stable virologic response. Study objective: determination of virologic response predictors in CVHC patients when various therapeutic schemes are used. Materials and methods: Group 1 of CVHC 52 patients with genotype 1 of HCV received standard anti-viral therapy, Group 2 (21 subject) – interferon-free scheme (Viekira Pak+ Ribavirin). Genetic polymorphisms IL-28В rs12979860 (С>Т) and rs8099917 (Т>G) and blood interferon-γ induced protein – IP-10 were determined. Results: standard anti-viral therapy in Group 1 resulted in SVR (sustained viral response) in 29 patients (55.7%). In Group 2 that received Viekira Pak 100% SVR was achieved in spite of more frequent F3 and 4 stage of fibrosis, unsuccessful anti-viral therapy (9 persons), contraindications to IFN-α drugs (6 persons). Unfavorable genotypes IL-28B ТТ (rs12979860) and GG (rs8099917) were associated in Group 1 with lack of SVR, level of IP-10 in patients with SVR was lower than the one in non-respondents. The therapy by Viekira Pak was well tolerated and resulted in SVR despite presence of grave hepatic fibrosis/ cirrhosis, concomitant pathology, unfavourable options of IL-28B, high IP-10 protein levels. Conclusion: choice of optimal anti-viral therapy schemes for each patient with CVHC must be done taken into account all possible predictors, which allows optimizing the therapy and preventing the necessity of repeated therapy.

Summary: the article presents the results of the examination of patients with chronic viral hepatitis C namely the study of the informativeness of instrumental (fibroelastography) and serological (the content of hyaluronic acid in serum) of markers of fibrosis by assessing their predictive value by ROC- analysis. The purpose of the study: to find out the possibility of non-invasive methods for diagnosing liver fibrosis in patients with chronic viral hepatitis C (CHC). Materials and methods 66 patients with CHC with the 1-st genotype of the virus were examined, which were at the dispensary observation and ambulatory treatment at DCC CCH №1 in Vinnitsa and in the clinical department of viral hepatitis at the Institute of Epidemiology and Infectious Diseases named after L.V. Gromashevsky NAMS of Ukraine. All patients received fibroelastography (FEG) with a METAVIR score. All patients with CHC and group of control determined the content of hyaluronic acid (GA) in blood serum (ELISA using the Hyaluronic Acid (Corgenix, Inc., USA)). Research results Sensitivity of determination of GA in blood serum of patients with CHC with degree of fibrosis of liver F0-F2 was 91.23%, and specificity - 90.46%. For the FEG method, respectively: 74.33% and 77.25%. In the group of patients with degree of fibrosis F3 sensitivity of the definition of GA in blood serum was 72.21%, and specificity - 74.71%. The corresponding qualitative characteristics for FEG were: 98.32% and 91.45% respectively. The sensitivity of the determination of the content of GA in serum of patients with CHC with the degree of liver fibrosis F4 was 88.23%, and the specificity was 92.12%. For these patients the sensitivity and specificity of determining the degree of fibrosis by the FEG method were 87.78% and 91.45% respectively. Conclusions High diagnostic efficiency of determination of the content of GA in serum was established for assessing the degree of liver fibrosis in patients with CSF (AUC = 0,720-0,917, p˂0,01). Relatively higher sensitivity and specificity of the diagnosis of liver fibrosis was observed in determining the content of GA in serum compared with the FEG method (AUC = 0.914 vs. AUC = 0.817 (p˂0.05)) in the group with a lack or initial signs of liver fibrosis (F0-F2).

The results of chronic viral hepatitis C patients examinations are described. A comparative characteristic of the diagnostic informative value of direct (hyaluronic acid) and indirect (alanine aminotransferase, aspartate aminotransferase, de Ritis coefficient) of liver fibrosis markers by the use of ROC - analysis is presented. The objective: to explore the possibility of non-invasive methods for diagnosing liver fibrosis in patients with chronic viral hepatitis C (CVH C). Materials and methods. 66 CVH C with the 1st genotype of the virus were examined. They were either at dispensary observation or ambulatory treatment at Municipal Clinical Hospital №1 (Vinnitsa, Ukraine) and in the clinical department of viral hepatitis at L. V. Gromashevsky Institute of Epidemiology and Infectious Diseases of NAMS (Ukraine). All patients underwent fibroelastography (FEG) on the METAVIR fibrosis score. In all CVH C patients and control group individuals content of hyaluronic acid (HA) in blood serum was determined. ELISA method and “Hyaluronic Acid” kit (Corgenix, Inc., USA) were used. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity was investigated with kinetic method (analyzer and test system Cobas 6000, Roche Diagnostics, Switzerland). Results: AUC for HA content in serum of CVH C patients was in the range 0.720-0.917 (p

The second-generation of direct-acting antiviral agents are the current treatment for chronic viral hepatitis C infection. To evaluate the regression of liver fibrosis in patients receiving this therapy, liver biopsy remains the most accurate method, but the invasiveness of this procedure is its major drawback. Different non-invasive tests have been used to study changes in the stage of liver fibrosis in patients with chronic viral hepatitis treated with the second-generation of direct-acting antiviral agents: liver stiffness measurements (with transient elastography or acoustic radiation force impulse elastography) or different scores that use serum markers to calculate a fibrosis score. We prepared a literature review of the available data regarding the long-term evolution of liver fibrosis after the treatment with direct-acting antiviral agents for chronic viral hepatitis C. [ABSTRACT FROM AUTHOR]