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Aim – to assess the effect of the order and time of HIV/HCV and HIV/HBV co-infections, as well as the antiretroviral therapy regimen on the progression of fibrotic changes in the liver. Material and methods. The object of the retrospective-prospective clinical study was 204 HIV/HCV co-infected patients, and 30 HIV/HBV co-infected patients, divided into groups according to the type of viral pathogen that first entered the patient's body. The criterion for assessing the patients' condition was the type of the liver fibrous process (progressive, stable, regressing) according to the annual transient ultrasound elastography of the liver. Results. It was found that the order of pathogens entry significantly affected the progression of liver fibrosis. The least favorable situation arose when the first pathogen was HIV, and the interval between the entry of viral pathogens into the patient's body was more than 5 years. The degree of the fibrotic process progression was also influenced by the combination of drugs with different action mechanisms for antiretroviral therapy. Conclusion. The risk of progressive liver fibrosis in HIV/HCV co-infection patients was associated with a situation where the first infecting pathogen was HIV, and an interval between co-infections was more than 5 years. In this case, the most optimal antiretroviral therapy regimen was a combination of nucleoside reverse transcriptase inhibitors with integrase inhibitors. In HIV/HBV co-infection, the risk group for progressive liver fibrosis included patients having HIV as the first pathogen and an interval between co-infections 5-10 years, as well as patients having HBV as the first pathogen with an interval between the infectious agents more than 10 years. The most optimal regimen of antiretroviral therapy was a combination of nucleoside reverse transcriptase inhibitors, which also have anti-HBV effect, with protease inhibitors.

Background. Despite active research, drug treatment options for metabolic associated fatty liver disease (MAFLD) are limited, and there are no currently approved drugs for patients with MAFLD. Treatment of patients at risk of developing non-alcoholic steatohepatitis and progressive liver fibrosis (LF) is of particular relevance, since they determine the clinical outcomes of the disease. Aim. To evaluate the clinical efficacy of complex polypeptide drug (CPD), human placenta hydrolyzate, containing low molecular weight regulatory peptides, amino acids, vitamins, macro- and microelements in patients with MAFLD at the LF stage. Materials and methods. A single-center, placebo-controlled pilot study. Patients with MAFLD at LF stage 1≤F≤3 according to METAVIR were included (n=10, of which 8 were women, median age was 55 years old). Patients were randomized into 2 groups: 5 people received CPD therapy for 12 weeks (intravenous infusion of 6 ml 2 times a week); another 5 people initially received placebo x 2 times a week (12 weeks), with transfer to the open phase for CPD therapy in the same regimen. The dynamics laboratory and instrumental data was assessed, as well as determine the presence of fibrosis by non-invasive tests – measurement of liver stiffness by transient elastography and use of serum biomarker (SM) by FibroTest and detection of steatosis with controlled attenuation parameter for transient elastography and SM by SteatoTest. The quality of life of patients was assessed using questionnaire SF-36 and well-being via Visual Analogue Scale. Statistical processing of the material was carried out using the methods of nonparametric analysis, using the Statistica 13.3 software. Results. Patients in the CPD group compared with the baseline data and with the placebo group showed a statistically significant improvement: 1) transaminases (ALT, AST), lipid profile indicators (cholesterol), ferritin; 2) indicators of LF, based on a decrease in liver stiffness by transient elastography and SM of Fibrotest, as well as the degree of steatosis based on controlled attenuation parameter and SM of Steatotest; 3) in well-being and quality of life (according to testing: SF-36 physical, mental well-being and general condition of the VAS). CPD was well tolerated, no side effects were noted. Conclusion. In patients with MAFLD during CPD therapy, a decrease in the level of liver enzymes was noted, as well as in LF and liver steatosis according to noninvasive methods. Randomized controlled trials are required to confirm these findings.

BACKGROUND: The diagnosis of liver fibrosis is an important task in the management of patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The currently used diagnostic methods have a number of disadvantages such as invasiveness and high cost, or insufficient sensitivity and specificity. Therefore, the search for new non-invasive markers of liver fibrosis remains an actual challenge.AIM: To assess a diagnostic value of serum growth differentiation factor-15 (GDF-15), microfibril-associated glycoprotein 4 (MFAP-4), collagen type IV alpha1 (COL4alpha1), Mac-2 binding protein (M2BPGI) and chitinase-3-like protein 1 (YKL-40) as markers of liver fibrosis in patients with type 2 diabetes and NAFLD.MATERIALS AND METHODS: A single center cross-sectional observational study was performed. The study included 74 patients, 23 men and 51 women, aged 18 to 74 years. Liver elastography was used as reference method for the fibrosis evaluation. APRI and fib-4, non-invasive fibrosis indices, were assessed. Serum concentrations of GDF-15, MFAP-4, COL4alpha1, M2BPGI, and YKL-40 were determined by ELISA. ROC analysis was used to evaluate the sensitivity and specificity of serum markers for the diagnosis of the liver fibrosis.RESULTS: Liver fibrosis stage 1 was verified in 16 subjects, stage 2 in 12, stage 3 in 7, and stage 4 in 19. Patients with advanced liver fibrosis (stages 3–4), compared with those without severe fibrosis (stages 0–2), had higher levels of GDF-15 (p=0.003), COL4alpha1 (p=0.007), and YKL-40 (p=0.04). Patients with stage 1-2 liver fibrosis had higher levels of COL4alpha compared to those without any signs of fibrosis (p=0.02). There were no significant differences in the level of MFAP-4 and M2BPGI between patients with different severity of fibrosis. According to the ROC analysis, GDF-15, COL4alpha1 and YKL-40 have diagnostic value in the detection of severe liver fibrosis comparable to that of the APRI and fib-4 indices.CONCLUSION: GDF-15, COL4alpha1 and YKL-40 could be considered as promising non-invasive markers of liver fibrosis in patients with type 2 diabetes and NAFLD.

Aim of the study was to estimate the blood serum level of microtubule-associated protein 1 light chain 3 alpha (MAP1LC3alpha), beclin-1 (BECN-1), Bcl-2 (BCL-2), caspase-3 (CASP3) and autophagy related 5 (ATG-5) protein as potential markers of liver fibrosis in type 2 diabetes (T2D) patients with non-alcoholic fatty liver disease (NAFLD).Material and methods. A single center cross-sectional observational study was performed. Seventy four patients with T2D and NAFLD were included, 23 men and 51 women, aged 18 to 74 years. Transient elastography was used for the assessment of liver fibrosis. The severity of fibrosis was estimated using the Metavir sсore. In addition, indirect liver fibrosis indices APRI and FIB-4 were calculated. Serum concentration of MAP1LC3alpha, BECN-1, BCL-2, CASP and ATG-5 was measured by ELISA. We applied ROC analysis to assess the value of studied indicators in diagnosis of liver fibrosis.Results. Liver fibrosis stage F1 was verified in 16 subjects, stage F2 in 12, stage F3 in 7, and stage F4 in 19 individuals. Patients with advanced liver fibrosis (stage 3-4) when compared to those without fibrosis (stage 0–2) had higher content of MAP1LC3alpha (p = 0.01) and BECN-1 (p = 0.01). There were no significant differences in the level of BCL-2, CASP3 and ATG-5 between patients with different severity of fibrosis. In the ROC analysis, MAP1LC3alpha and BECN-1 showed significance for the diagnosis of severe liver fibrosis, which, however, did not exceed that of the APRI index.Conclusions. In patients with T2D and NAFLD, serum levels of MAP1LC3alpha and BECN-1 are associated with severe liver fibrosis.

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.

Rationale: The first direct anti-viral agents (DAVA) for the treatment of adolescents with chronic hepatitis C virus (HCV) infection have been approved quite recently, i. e. in 2017 worldwide and in 2019 in Russia. Currently, only few adolescents are treated worldwide, their proportion in the Russian Federation not exceeding 9 to 15%. The results of real-world practice with various DAVA regiments in adolescents aged 12 to 17 years could be useful to choose the strategies for local healthcare bodies. Aim: To evaluate the efficacy and safety of the fixed combination of glecaprevir and pibrentasvir (GLE/PIB) in adolescents aged 12 to 17 years with HCV infection genotypes (GT) 1 and 3 in the Moscow region. Materials and methods: We retrospectively analyzed the results of treatment of 32 adolescents (gender ratio 1:1) who were treated for HCV infection (GT1, 49.9% of the cases, GT3, 53.1%; F1 fibrosis according to the METAVIR scale, 37.5% of the patients, F2, 9.4%) with GLE/PIB during 2019 to 2022 within the Program of State-guaranteed free medical care to the citizens of the Moscow region. The treatment course lasted for 8 weeks in 31 treatment-nave patients and 16 weeks in one patient who had failed on interferon treatment. The information was extracted from medical files of the patients treated on the outpatient basis and from discharge letters from the day care unit. Concomitant diseases were diagnosed in 75% of the adolescents. Results: At week 4 of GLE/PIB treatment, HCV RNA was undetectable in 90.6% (95% confidence interval (CI) 75.098.0) of the patients, and alanine aminotransferase activity reached the reference interval in all patients (100%). The rate of sustained viral response at 12 week of therapy was 96.9% (95% CI 83.899.9), including 100% (95% CI 78.2100) in the GT1 patients and 94.1% (95% CI 71.399.9) in the GT3 patients. At week 24 after the GLE/PIB treatment had been finished, the rate of liver fibrosis according to METAVIR decreased from 46.9% to 12.5% (p 0.001). The lack of response to GLE/PIB in one patient with GT1 HCV appeared to be due to missed doses of the drug. GLE/PIB-related adverse events (headache, fatigue, nausea, and diarrhea) were rare and were recorded in 9.4% (95% CI 1.925.0) of the patients, whereas unrelated adverse events (acute respiratory infection symptoms) in 15.6% (95% CI 5.332.8) of the patients. All adverse events were mild, occurred at 23 weeks of the treatment and did not require additional pharmacological intervention. Conclusion: The results obtained indicate a high efficacy and safety profile of GLE/PIB for the treatment of chronic HCV infection in adolescents aged 12 to 17 years. They can be used by local healthcare authorities to choose the treatment regimens effective for all genotypes and most suitable for children.

Modern antiviral therapy regimens for patients with chronic viral hepatitis aim to achieve either long-term suppression of pathogen replication (e.g., nucleoside analogs in chronic hepatitis B) or complete elimination of the virus (such as direct-acting antiviral drugs in chronic hepatitis C). However, antiviral agents do not have a significant impact on the complete restoration of biochemical processes or the prevention of further progression of morphological changes in the liver. These limitations emphasize the ongoing need for new therapeutic strategies that target the processes of fibrogenesis. The aim of the work is to assess the possibility of the effect of the drug "Bicyclol" on fibrotic changes in patients with chronic hepatitis B+C using a non-invasive scale of the rate of fibrosis. Materials and methods An analysis of the dynamics of 62 patients with chronic hepatitis B and C (HCV+C) was conducted. All patients received long-term antiviral therapy consisting of pegylated interferon for 48 weeks. In the main group (Group I), patients with chronic hepatitis B and C were prescribed the drug "Bicyclol" after completing antiviral treatment with interferon. The control group (Group II) followed the principles of proper nutrition and took traditional hepatoprotectors. Based on the identified correlations, a non-invasive scale was proposed to assess the individual risk of liver fibrosis progression. Research results Against the background of the use of an antiviral treatment regimen, the normalization of cytolysis indicators was observed in most patients with CHB+C, but in some patients it was short-lived. Treatment with the drug "Bicyclol" contributed to a further decrease in cytolysis indicators, in the vast majority of patients with CHB+C, the activity of ALT and AST reached the upper limit of the norm. In patients with CHB+C who received only basic treatment without an antifibrotic component, a tendency to maintain an elevated level of transaminases was observed. Conclusions. Thus, the use of the hepatoprotector "Bicyclol" for 12 months ensures a decrease in cytolysis in the liver, is accompanied by a decrease in the severity of fibrosis, and in some patients - its reverse development. The use of the proposed prognostic scale makes it possible to assess the need for early appointment of antifibrotic therapy.

Aim. The purpose of our work is to find out diagnostic values of serum MMP-9 and TGF-1β determination for assessing the severity of liver fibrosis and the rate of its progression in patients with chronic hepatitis C genotype 1 (CHC GT1) infection. Materials and methods. 92 patients with CHC GT1 were examined. The severity of liver fibrosis was assessed by elastometry. The rate of liver fibrosis progression was calculated using the T. Poynard formula. Serum levels of TGF-1β and MMP-9 were measured by ELISA method. Results. In patients with CHC GT1, the most noticeable changes in the serum parameters of fibrogenesis / fibrinolysis were observed in the presence of F 3–4. The probability of liver fibrosis stages F 3–4 was high at the serum levels of TGF-1β >12.03 pg/ml (p < 0.001), MMP-9 ≤987.20 pg/ml (p = 0.016), TGF-1β/MMP-9 ratio >0.011 (p < 0.001). Fast liver fibrosis progression was more often registered in F 3–4 than in F 0–2 (62.9 % vs. 16.7 %, p < 0.0001). Increasing rate of liver fibrosis progression in these patients was confirmed by a higher ratio of TGF-1β/MMP-9 compared to that in patients with a slow rate of liver fibrosis progression (p < 0.05). The probability of fast liver fibrosis progression was high at the serum levels of TGF-1β >8.69 pg/ml (p < 0.001), MMP-9 ≤920.65 (p = 0.005), TGF-1β/MMP-9 ratio > 0.011 (p < 0.001). Conclusions. The diagnostic value of MMP-9 and TGF-1β in assessing the liver fibrosis severity and the rate of its progression in patients with CHC GT1 has been defined. Cut-off levels of MMP-9, TGF-1β and the TGF-1β/MMP-9 ratio for stratification of patients with severe liver fibrosis and the fast rate of its progression have been proposed.

The purpose of the study was to analyze the external influences and characteristics of the state of the organism being examined, which affect the results of ultrasonic elastography of the liver. Internal confounding factors include: inflammation and some other, besides fibrosis, liver pathology: amyloidosis, hemochromatosis, toxic hepatitis, lymphoma, cysts, tumors, veno-occlusive liver disease, as well as the degree of hydration, circulatory failure, renal failure, obesity, ascites, pregnancy, biliary hypertension and other less significant factors. External confounding factors are: food, alcohol; smoking and pharmaceutical preparations. The elastographic index of liver fibrosis is affected by the severity of its inflammation. Active hepatitis with a fivefold or more increase in aspartic aminotransferase and/or alanine aminotransferase overestimates the results of liver stiffness and does not enable a reliable investigation. With obstructive jaundice, in the absence of significant initial liver damage, Young’s modulus usually increases twofold to threefold. After biliary decompression by percutaneous bile duct drainage, Young’s modulus decreases. The presence of confounding factors should be indicated in the study protocol.

In this study we compared methylation levels of 27,578 CpG sites between paired samples of the tumor and surrounding liver tissues with various degrees of damage (fibrosis, cirrhosis) in HCV-induced hepatocellular carcinoma (HCC) patients, as well as between tumor and normal tissue in non-viral HCC patients, using GSE73003 and GSE37988 data from GEODataSets (https://www.ncbi.nlm.nih.gov/). A significantly lower number of differentially methylated sites (DMS) were found between HCC of non-viral etiology and normal liver tissue, as well as between HCC and fibrosis (32 and 40), than between HCC and cirrhosis (2450 and 2304, respectively, according to GSE73003 and GSE37988 datasets). As the pathological changes in the tissue surrounding the tumor progress, the ratio of hyper-/ hypomethylated DMSs in the tumor decreases. Thus, in tumor tissues compared with normal/fibrosis/cirrhosis of the liver, 75/62.5/47.7 % (GSE73003) and 16 % (GSE37988) of CpG sites are hypermethylated, respectively. Persistent hypermethylation of the ZNF154 and ZNF540 genes, as well as CCL20 hypomethylation, were registered in tumor tissue in relation to both liver fibrosis and liver cirrhosis. Protein products of the EDG4, CCL20, GPR109A, and GRM8 genes, whose CpG sites are characterized by changes in DNA methylation level in tumor tissue in the setting of cirrhosis and fibrosis, belong to “Signaling by G-protein-coupled receptors (GPCRs)” category. However, changes in the methylation level of the “driver” genes for oncopathology (АРС, CDKN2B, GSTP1, ELF4, TERT, WT1) are registered in tumor tissue in the setting of liver cirrhosis but not fibrosis. Among the genes hypermethylated in tumor tissue in the setting of liver cirrhosis, the most represented biological pathways are developmental processes, cell-cell signaling, transcription regulation, Wnt-protein binding. Genes hypomethylated in liver tumor tissue in the setting of liver cirrhosis are related to olfactory signal transduction, neuroactive ligand-receptor interaction, keratinization, immune response, inhibition of serine proteases, and zinc metabolism. The genes hypermethylated in the tumor are located at the 7p15.2 locus in the HOXA cluster region, and the hypomethylated CpG sites occupy extended regions of the genome in the gene clusters of olfactory receptors (11p15.4), keratin and keratin-associated proteins (12q13.13, 17q21.2, and 21q22.11), epidermal differentiation complex (1q21.3), and immune system function loci 9p21.3 (IFNA, IFNB1, IFNW1 cluster) and 19q13.41–19q13.42 (KLK, SIGLEC, LILR, KIR clusters). Among the genes of fibrogenesis or DNA repair, cg14143055 (ADAMDEC1) is located in the binding region of the HOX gene family transcription factors (TFs), while cg05921699 (CD79A), cg06196379 (TREM1) and cg10990993 (MLH1) are located in the binding region of the ZNF protein family transcription factor (TF). Thus, the DNA methylation profile in the liver in HCV-induced HCC is unique and differs depending on the degree of surrounding tissue lesion – liver fibrosis or liver cirrhosis.

The aim of the study is a systematic analysis of literature data on the effect of methodological factors, artifacts, as well as external influences and features of the state of the organism on the results of ultrasonic elastography of the liver. Two-dimensional shear wave elastography is a highly accurate method for assessing the degree of liver fibrosis, provided that the study methodology is strictly followed, however, the influence of measurement disturbances should be taken into account. Confounding factors lead to an erroneous change in the liver stiffness from insignificant, within 5-10%, to considerable, catastrophically distorting the assessment of the degree of liver fibrosis. Confounding factors include three main groups: 1) methodologically determined, as well as physical artifacts and equipment features; 2) internal (endogenous) and 3) external (exogenous). The first group of confounding factors includes: non-observance by the operator of the standard rules for manipulating the probe, positional features of the patient, insufficient size of the window area of the area of interest, incorrect location of the area of interest, lack of adequate breath holding by the patient or the performing of his/her movements, insufficient number of measurements, large spread of recorded values, transmission pulsations from the heart and large vessels, features of the equipment used, physical essence of the elastographic method and artifacts.

Aim: to analyze the dynamics of fibrosis and steatosis of the liver according to fibroelastometry in patients with chronic hep-atitis C (CHC) after ≥ 6 months from transient elastometry (TE) achieving a sustained virologic response (SVR) to antiviral therapy.Materials and methods. At baseline, a prospective observational study included 628 CHC patients with known stage of liver fibrosis (F) before AVT, some of whom were phased out due to non-compliance with the inclusion criteria. The final analysis included 297 patients who had transient elastometry (TE) data with CAP™ technology on the severity of liver fibrosis (± steatosis) before treatment and after ≥ 6 months after reaching SVR (67 % – interferonfree regimens of therapy). Median follow-up from the moment SVR was confirmed was 3 years [2; 6].Results. At the end of the study, the average age of patients was 49 ± 12 years, of which 53 % were men. In the long-term period after reaching SVR, regression of liver fibrosis was diagnosed in 80 % of cases (including in patients with cirrhosis), and the progression of fibrosis was in 3 % of patient. At the same time, regression of liver steatosis was detected only in 31 % of the patient, worsening of the results was in 23 % (26 % of them had the appearance of steatosis (S) of the liver of 1–3 degrees in persons with no fatty liver before the start of AVT). In the group of patients with liver steatosis, the proportion of men was significantly higher (p = 0.004). Clinically significant stages of fibrosis F3–F4 were significantly more often recorded in patients with hepatic steatosis, both before treatment (46 % S1–S3 and 22 % S0, p < 0.001) and after ≥ 6 months after reaching SVR (19 % S1–S3 and 9 % S0, p = 0.023).Conclusion. In patients with chronic hepatitis C with SVR achieved in the long term, despite a significant regression of liver fibrosis, a high prevalence of hepatic steatosis remains. The data obtained indicate the feasibility of routine diagnosis of both fibrosis and steatosis of the liver in the management of patients with chronic HCV infection before and after successful antiviral therapy.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, which includes changes from hepatic steatosis and nonalcoholic steatohepatitis to fibrosis and cirrhosis. Attempts to find noninvasive markers of liver fibrosis have led to a variety of scales, diagnostic algorithms, and imaging techniques. Individual studies have analyzed the relationship between the FINDRISC scale and hepatic steatosis and concluded that this questionnaire can be used as part of population screening to identify individuals at risk for hepatic steatosis. However, our review of the literature did not reveal any clinical studies on the use and effectiveness of the FINDRISC in liver fibrosis screening.AIM: To evaluate diagnostic value of FINDRISC for liver fibrosis detection.MATERIALS AND METHODS: The study enrolled patients aged 40–60 years from unorganized outpatient population. The sample of patients was formed randomly according to the inclusion and noninclusion criteria. All patients were assessed with standard anthropometric parameters. The FINDRISC questionnaire was used. All patients underwent transabdominal ultrasound examination of the liver and transient liver elastometry. The degree of steatosis was evaluated using Hamaguchi ultrasound scale. RESULTS: The study included 100 patients. An increased risk of type 2 DM (≥7 points) was detected in 68% of patients using the FINDRISC scale. Liver steatosis was diagnosed in 41% of patients. Median values of hepatic elastic modulus by transient elastometry were 4.50 (4.00; 5.25) kPa. At the same time, liver elasticity modulus values ≥5.9 kPa were registered in 11 (11.0%) patients. When analyzing the array of sensitivity and specificity values using the ROC-curve, it was found that for the FINDRISC scale the maximum LR+ and the minimum LRvalues were observed when the number of points on the indicated scale exceeded 10. At this cutoff, the FINDRISC scale had a sensitivity of 81.8% and specificity of 61.8% for detecting liver fibrosis (liver modulus of elasticity ≥5.9 kPa). The scale was of good diagnostic value (AUC 0.699; 95% CI 0.530–0.815).CONCLUSION: In an unorganized sample of patients aged 40–60 years the FINDRISC can serve as a diagnostic tool for liver fibrosis and steatosis. Sum of FINDRISC scores >10 allowed to diagnose liver fibrosis (liver elastic modulus ≥5.9kPa) with sensitivity 81.8% and specificity 61.8%. The probability of absence of hepatic fibrosis with FINDRISC scale values

Aim: present clinical guidelines, aimed at general practitioners, gastroenterologists, cardiologists, endocrinologists, comprise up-to-date methods of diagnosis and treatment of non-alcoholic fatty liver disease.Key points. Nonalcoholic fatty liver disease, the most wide-spread chronic liver disease, is characterized by accumulation of fat by more than 5 % of hepatocytes and presented by two histological forms: steatosis and nonalcoholic steatohepatitis. Clinical guidelines provide current views on pathogenesis of nonalcoholic fatty liver disease as a multisystem disease, methods of invasive and noninvasive diagnosis of steatosis and liver fibrosis, principles of nondrug treatment and pharmacotherapy of nonalcoholic fatty liver disease and associated conditions. Complications of nonalcoholic fatty liver disease include aggravation of cardiometabolic risks, development of hepatocellular cancer, progression of liver fibrosis to cirrhotic stage.Conclusion. Progression of liver disease can be avoided, cardiometabolic risks can be reduced and patients' prognosis — improved by the timely recognition of diagnosis of nonalcoholic fatty liver disease and associated comorbidities and competent multidisciplinary management of these patients.

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are the most important regulators of growth, regeneration and metabolism. The influence of GH and IGF-1 on pediatric liver transplant outcomes is mediated through growth and body weight regulation, specific effects on hepatocyte function and immune system activity. In recent years, the blood levels of these factors and life expectancy, both in healthy individuals and liver recipients, have been shown to be correlated. In pediatric liver recipients, neurohumoral regulation of graft function and other functions of the growing organism, has not been studied enough. The results of studies on the levels and dynamics of GH and IGF-1 in the blood of liver recipients can serve as a basis for assessing the state of graft using new minimally invasive methods and identifying therapeutic targets for personalized therapy. This review summarizes the current understanding of the significance of GH/IGF-1 hormones in hepatobiliary diseases and pediatric liver transplantation (LTx).

Introduction. There is a discussion about which genotype of viral hepatitis C (HCV) is the most aggressive. Some authors consider that the 1st genotype is the most aggressive, others define the 3rd HCV genotype as a factor that determines the high activity of the pathological process. The solution of this issue is important for optimizing the tactics of patient management.Aim. To compare the clinical and laboratory characteristics and the incidence of liver fibrosis in patients with chronic viral hepatitis C of the first and third genotypes.Materials and methods. 297 patients with genotype 1 of HCV and 231 patients with genotype 3 of HCV were examined. The diagnosis of chronic viral hepatitis C was established according to the recommendations of the European Association for the Study of the Liver (2016, 2018). Liver fibrosis was studied by shear wave transient elastometry with METAVIR score.Results and discussion. The frequency of elevated ALT in the blood prevailed in patients with HCV genotype 3 compared with persons with HCV genotype 1 (90.5% vs. 82.8%, p = 0.02). ALT levels above 3 norms were registered in 29.0% of patients with genotype 3 and in 16.8% patients with HCV genotype 1 (p = 0.001). The frequency of liver fibrosis F2 according to METAVIR was 11.8% in patients with genotype 1 and 21.2% in patients with genotype 3 of HCV (p = 0.005); the frequency of liver fibrosis F3–F4 according to METAVIR was 20.5% in patients with genotype 1 and 32.5% in patients with genotype 3 of HCV (p = 0.003). The combination of high viral load and high inflammatory activity, which was associated with liver fibrosis F3–F4 according to METAVIR in both compared groups, was determined in 16.9% of patients with genotype 3 and only in 10.4% of patients with genotype 1 of HCV (p = 0.04).Conclusion. The obtained data allow us to consider that in the surveyed population the course of chronic viral hepatitis C with genotype 3 is clearly more aggressive than in persons with genotype 1 of HCV.

One of the features of the spread of infectious diseases is an increase in the number of mixed infections caused by various types of microorganisms: bacteria, viruses, protozoa, fungi, mycoplasmas, chlamydia, etc. In mixed infections, the simultaneous presence of several pathogens leads to not only to the complex interaction of pathological processes, but also complicates the diagnosis and choice of treatment. Mixed hepatitis is characterized by high biochemical activity and histological changes, the presence of signs of portal hypertension. Infection with two viruses increases the risk of developing hepatocellular carcinoma. It should be noted that in patients with HBV infection, the development of hepatocellular carcinoma is possible at the stage of chronic hepatitis before the onset of liver cirrhosis. The aim of the study: to investigate a comprehensive assessment of the allelic polymorphism of the IL-4 (rs2243250), IL-10 (rs1800896), TNFα (rs1800620), SMAD family member 7 (rs4939827) and eIF3h (rs16892766) genes with the degree of fibrosis in patients with chronic hepatitis B&C. Materials and methods. In the course of the study, 62 patients with chronic hepatitis B&C were examined before the start of treatment and after the end of the course of antiviral therapy. The degree of liver fibrosis was established by FibroScan. Molecular genetic studies included the determination of polymorphic variants of the IL-4 (rs2243250), IL10 (rs1800896), TNFα (rs1800620), SMAD family member 7 (rs4939827), eIF3h (rs16892766) genes. Polymorphism was studied by amplification of the corresponding regions of the genome by PCR. Results and discussions. Genotypes CC IL-4 (rs2243250), GG IL-10 (rs1800896), GG TNFα (rs1800620), AA SMAD family member 7 (rs4939827), TT eIF3h (rs16892766) have a protective effect on the course of chronic hepatitis B&C, as they are established in patients with chronic hepatitis B&C with a lower degree of fibrosis. Heterozygous CT IL-4 (rs2243250), GA IL-10 (rs1800896), GA TNFα (rs1800620), CC SMAD family member 7 (rs4939827), CC eIF3h (rs16892766) have a profibrotic effect on the course of chronic hepatitis B&C, therefore that they are established in patients with chronic hepatitis B&C with a greater degree of fibrosis.In patients with a low stage of fibrosis, the genotypes CC IL-4 (rs2243250), GG IL-10 (rs1800896), GG TNFα (rs1800620), AA SMAD family member 7 (rs4939827), TT eIF3h (rs16892766), are most often determined. In patients with a degree of fibrosis, other genotypes were detected, namely CT IL-4 (rs2243250), GA IL-10 (rs1800896), GA TNFα (rs1800620), CC SMAD family member 7 (rs4939827), CC eIF3h (rs16892766). Сonclusions. The revealed differences in the frequency of occurrence of various gene polymorphisms in healthy subjects and patients with chronic hepatitis indicate a certain predisposition to the development of a chronic inflammatory process in the liver.

Aim. An overview of current pharmacotherapy for non-alcoholic steatohepatitis (NASH)-associated liver fibrosis.Key points. In current clinical recommendations, therapeutic measures in non-alcoholic fatty liver disease should include lifestyle change, body weight normalisation, NASH-associated liver fibrosis-specific drug therapy and treatment for metabolic syndrome-related diseases. Given a lack of approved antifibrotic therapies in NASH, several drugs have nevertheless demonstrated an adequate efficacy and safety in phase 3 clinical trials, also in compensated cirrhosis, which allows their practical validation in phase 4.Conclusion. The understanding of liver fibrosis as an adverse natural consequence of non-alcoholic fatty liver disease clearly attests for an early introduction and wide use of antifibrotic therapy to improve NASH outcomes and avoid associated complications.

Aim. To study the activity of neutrophilic granulocytes in patients with opisthorchiasis, depending on the severity of liver fibrosis. Materials and methods. A total of 74 patients with chronic opisthorchiasis (39 men and 35 women, average age 42.3 years) and 32 practically healthy patients (17 men and 15 women, average age 41.5 years) aged 24 to 60 years were examined. Diagnosis of opisthorchiasis was carried out by two methods: coprooscopy and identification of eggs or bodies of adult parasites in duodenal content. Liver fibrosis was determined by the method of elastometry according to the METAVIR scale in all 74 patients with opisthorchiasis. The study of the functional activity of neutrophils in the blood was performed to all 74 patients with opisthorchiasis and 32 healthy individuals from the control group by chemiluminescent analysis with measurement of the reactive oxygen species (ROS) production intensity in a spontaneous and zymosan-induced reaction in lucigenin and luminol-dependent processes. Results. Liver fibrosis F2 by METAVIR was registered in 20.3% of the examined individuals, liver fibrosis F3F4 by METAVIR was detected in 17.6% of patients with opisthorchiasis. In patients with opisthorchiasis with liver fibrosis F3F4 by METAVIR, a significant decrease in the functional activity of neutrophilic granulocytes was registered in comparison with individuals with liver fibrosis F0F1 by METAVIR, as evidenced by a significant decrease in the maximum intensity of ROS production (Imax) and the area under the curve (S) chemiluminescence in lucigenin and luminol-dependent processes both in the spontaneous and zymosan-induced reaction. Conclusion. These results provide new information to explain the mechanisms of liver fibrosis in patients opisthorchiasis and create opportunities for the development of diagnostics and preventive technologies.

The aim was to examine functional activity of peripheral blood neutrophilic granulocytes in patients with Opisthorchis felineus invasion and skin syndrome. Materials and methods. A total of 92 patients with chronic opisthorchiasis were examined, of which 38 patients (20 males and 18 females, average age 35.7±3.9 years) and 54 patients (28 males and 26 females, average age 36.5±4.1 years) with/without skin syndrome, as well as 32 apparently healthy subjects (17 males and 15 females, average age 41.5 years). Detection of adult parasite eggs or bodies in the duodenal contents and/or feces was used as the major diagnostic method of opisthorchiasis used in all 92 opisthorchiasis patients. Liver fibrosis was assessed by elastometry method according to the METAVIR scale in all 92 opisthorchiasis patients. Functional activity of peripheral blood neutrophilic granulocytes was examined in all 92 opisthorchiasis patients and 32 healthy individuals from the control group by chemiluminescent analysis measuring intensity of reactive oxygen species production in spontaneous and zymosan-induced reactions in lucigenin and luminol-dependent processes. Results. Opisthorchiasis patients with vs. without skin syndrome suffered at higher rate from pain in the right hypochondrium, dyspepsia, astheno-vegetative syndrome, skin itching, blood eosinophilia, hyperbilirubinemia, cholestatic syndrome, cholecystitis, hepatomegaly, and had elevated serum immunoglobulin E level. Liver fibrosis F3—F4 according to METAVIR was determined in 18.4% and 11.1% of opisthorchiasis patients with vs. without skin syndrome (OR = 1.78; CI 0.57—5.57; p = 0.05). Both luminol- and lucigenin-dependent processes in opisthorchiasis patients with vs. without skin syndrome revealed significantly decreased functional activity of neutrophilic granulocytes which was evidenced by significantly decreased maximum intensity of reactive oxygen species production and the area under the chemiluminescence curve both in spontaneous and zymosan-induced reaction. Conclusion. The results suggest that the presence of skin syndrome in patients with opisthorchiasis is accompanied by more prominent clinical and laboratory manifestations, decreased functional activity of peripheral blood neutrophils, thereby allowing to consider it as a marker of intense pathology.

Aim – to investigate the relationship between HBeAg status of patients with chronic hepatitis B and the content of TNF-α in the serum, the level of viral load and the severity of morphological changes in the liver according to non-invasive tests. Material and methods. 70 patients with CHB were examined. Noninvasive methods were used to determine the severity of morphological changes in the liver. The content of HBV-DNA in the blood was determined by PCR, HBeAg, anti-HBe, TNF-α by ELISA. Statistical processing was performed in Statistica 13 for Windows (StatSoft Inc., No. JPZ804I382130ARCN10-J). Results. HBeAg-negative patients (78.6 %) with anti-HBe (89.1 %) predominate among patients with CHB. Lower frequency of seroconversion in patients with stages F 2–4, compared with patients with stages F 0-1 (85.7 % vs. 100 %, P < 0.05). The highest level of HBV-DNA in the blood was in HBeAg-positive patients, compared with HBeAg-negative with stages F 0–1 (P < 0.05), of whom 83.3 % of patients had HBV-DNA >20000 IU/ml (83.3 % vs. 17.7 %). Viral load in HBeAg-positive patients with activity A 0–1 was the highest (P < 0.05), namely 4 times more often HBV-DNA was >20000 IU/ml, compared with HBeAg-negative (P < 0.05) A 0–1. The content of TNF-α in the serum of patients with CHB was higher than in healthy individuals (P < 0.05). The highest content of TNF-α in the blood in HBeAg-positive patients with F 2–4, compared with HBeAg-negative with F 2–4 (P < 0.05). The severity of liver fibrosis correlated with the level of TNF-α (r = 0.31, P < 0.05). Conclusions. HBeAg-negative (78.6 %) predominate among patients with CHB. In the presence of HBeAg-positive patients F 0–1 viral load is highest (P < 0.05). HBeAg-negative patients are 2.7 times more likely (P < 0.05) to have a viral load of HBV-DNA >20000 IU/ml in the presence of A 2–3 than in A 0–1. The highest content of TNF-α is in the serum of HBeAg-positive patients with F 2–4, compared with HBeAg-negative patients and the corresponding liver fibrosis (P < 0.05).

Introduction. The course of opisthorchiasis is accompanied by clinically diverse symptoms and severe complications up to the development of cholangiocarcinoma. The role of oxidative stress in the development of liver fibrosis is not well understood. Aim. To determine the association of clinical manifestations and indicators of oxidative stress in the blood with liver fibrosis in patients with Opisthorchis felineus invasion.Materials and methods. We examined 103 patients with chronic opisthorchiasis and 51 practically healthy patients. All patients underwent general clinical examinations, esophagogastroduodenoscopy and ultrasound examination of the abdominal organs, elastometry to assess liver fibrosis using the METAVIR system, and the content of malondialdehyde, catalase and superoxide dismutase in blood serum was determined by the immunoassay method.Results and discussion. Asthenic-vegetative syndrome, pain in the right hypochondrium, articular syndrome, cytolytic and cholestatic syndromes, hepatomegaly and signs of chronic cholecystitis were more often detected in patients with invasion of Opisthorchis felineus and liver fibrosis F3-F4 according to METAVIR. The content of malondialdehyde in the blood was 296.5 ng/ml in patients with liver fibrosis F3-F4 according to METAVIR and 69.5 ng/ml in patients with liver fibrosis F0-F1 according to METAVIR (p < 0.001). The content of superoxide dismutase and catalase did not differ significantly in the groups of patients with liver fibrosis F0-F1 according to METAVIR and F3-F4 according to METAVIR, which indicated insufficient effectiveness of antioxidant protection.Conclusion. The revealed changes indicate the presence in patients with opisthorchiasis of a pronounced association between the severity of the clinical course, the development of biochemical cytolysis syndromes and the severity of liver fibrosis and oxidative stress, which may be a promoter of inflammation, cell DNA damage and carcinogenesis.

The aim is to examine activity of peripheral blood monocytes from patients with opisthorchiasis coupled to intensity of liver fibrosis. Materials and Methods. A total of 74 patients with chronic opisthorchiasis (39 males and 35 females, average age 42.3 years) and 32 apparently healthy subjects (17 males and 15 females, average age 41.5 years) aged 24 to 60 years were enrolled. Opisthorchiasis was mainly diagnosed by parasitological assays to detect adult parasite eggs or bodies in duodenal contents and/or feces in all 74 patients. Liver fibrosis was assessed by elastometry according to the METAVIR scale. Functional activity of peripheral blood monocytes was performed in all patients with opisthorchiasis and healthy individuals from the control group by chemiluminescent analysis to measure intensity of reactive oxygen species production in lucigenin- and luminol-dependent spontaneous and zymosan-induced reactions. Results. Liver fibrosis F2 and F3—F4 stage according to METAVIR scale was found in 20.3% and 17.6% of patients with opisthorchiasis, respectively. While analyzing total pool of reactive oxygen species in the luminol-dependent process in patients with opisthorchiasis, a significantly decreased monocyte functional activity was observed as compared to healthy subjects that was evidenced by significantly decreased maximum intensity of produced reactive oxygen species as well as area under the chemiluminescence curve both in spontaneous and zymosan-induced reaction. Such parameters in liver fibrosis F3—F4 compared to F0—F1 in zymosan-induced response were lowered. Monocyte functional activity in spontaneous luminol-dependent reaction did not differ significantly depending on liver fibrosis intensity in patients with opisthorchiasis. The phagocytosis activation index in patients with opisthorchiasis with liver fibrosis F3—F4 compared to F0—F1 and F2 stage was lower. Similar changes were observed in the lucigenin-dependent reaction. Conclusion. The data obtained undoubtedly provide promising evidence to interpret the mechanisms behind liver fibrosis in patients with opisthorchiasis and create new opportunities for development of diagnostic and therapeutic technologies.

Aim. To assess the effect of metabolic disorders and galectin-3 levels on the progression of liver fibrosis in chronic hepatitis C. Materials and methods. 106 patients with HCV without decompensated liver cirrhosis were examined. Exclusion criteria: age younger than 20 and older than 65 years, diabetes, coronary heart disease, hypertension, alcoholism, drug addiction. Laboratory examination (biochemical blood test, enzyme immunoassay (ELISA) with determination of HCV-Ab antibodies, viral load) was supplemented with liver elastometry (Fibroscan) with fibrosis assessment (kPa, METAVIR scale). The body mass index of Quetelet (kg/m2), the presence of abdominal obesity, insulin resistance were evaluated. Serum levels of insulin and galectin-3 were determined by ELISA. Results. In 45% of patients, an increase in ITM was revealed, in 44% abdominal obesity, in 62% insulin resistance. In 75% abdominal obesity was determined in patients with liver fibrosis F3F4. Insulin resistance was found more often in patients with fibrosis F01 56.7%. Significant correlations between the level of galectin-3 and the degree of liver fibrosis (in kPa) [r=0,206, p=0,034], as well as the stage of liver fibrosis (on the METAVIR scale) [r=0,247, p=0,01] were obtained. The level of galectin-3 in liver cirrhosis was 6.32 (4.57; 9.64) ng/ml, which is significantly higher than in F0 3.96 (1.45; 5.30) ng/ml (p=0.002) and F1 3.85 (2.20; 5.83) ng/ml (p=0.002). By calculating the specificity and sensitivity of isolated for F4 stage of liver fibrosis (ROC-curve, the level of galectin-3 is 5.21 ng/ml), the level of specificity of 74.7%, sensitivity of 74% was established. Conclusion. We found a significant relationship between the disturbances of carbohydrate-lipid metabolism and liver fibrosis, the level of galectin-3 and fibrosis stage of the liver. The prognostic value of increasing the level of galectin-3 for predicting the cirrhotic stage of liver fibrosis is substantiated.

Liver fibrosis develops as a result of chronic liver damage of various etiologies, is characterized by excessive synthesis of connective tissue by activated stellate liver cells. The toxic effect of alcohol is one of the most significant and common etiological factors worldwide. Stellate cell activation results from the interaction of multiple molecular fibrogenic pathways triggered by intracellular and extracellular, hepatic and extrahepatic stimuli. Data analysis showed that knowledge about these abnormal pathways and biomolecular processes may further contribute to the improvement of approaches to assessment of disease prognosis and treatment of alcoholic liver disease.

Relevance: Most diffuse liver diseases lead to fibrosis over time with the risk of cirrhosis. With progressive fibrosis and cirrhosis of the liver both physical properties of the hepatic parenchyma and its hemodynamics change. The only reliable method for determining the stage of the disease is puncture biopsy and subsequent histological examination, but this method is invasive and associated with complications. Currently, the determination of the severity of cirrhosis is based on clinical data (the Child-Pugh scale) and elastography is considered to be the main non-invasive instrumental method. It lets reliably differentiate the initial fibrosis and cirrhosis of the liver, while the F2 and F3 stages according to the conventional METAVIR scale remain a "gray zone", as well as the differentiation of degrees of the severity of cirrhosis. In addition elastography has a number of limitations. The main ones of which are operator dependence, apparatus dependence and the inability to determine functional changes in the liver. With the use of perfusion computed tomography (CT perfusion) it is possible to assess the functionality of the liver by quantifying changes in hemodynamics. The method applied measures the characteristics of blood flow in the tissue at a given scanning level by computed-tomographic data on the dynamics of the distribution of the contrast agent in the area of interest is collected, besides the type of liver perfusion is determined. This parameter is needed to assess the dynamics of treatment against the background of drug therapy.Objective: To identify statistically significant parameters of CT perfusion to determine the severity of hemodynamic disturbances in patients with various stages of liver fibrosis and cirrhosis and to compare the values of parameters of liver CT perfusion with fibrosis according to the METAVIR conditional scale determined using elastography.Materials and methods: 18 patients were included in this parallel pilot study. On the basis of clinical and laboratory data and the results of elastography, 10 of them were diagnosed with fibrosis and cirrhosis. The stages of fibrosis F1, F2 were determined in 3 patients; stages F3, F4 – in 7. In the group of patients with F3, F4, according to the METAVIR conditional scale, subgroups were distinguished depending on the severity of cirrhosis: compensated – 3 patients, subcompensated – 2, decompensated – 2. The control group consisted of 8 patients with organ diseases abdominal cavity not associated with liver damage. All patients underwent CT perfusion of the liver on a Philips iCT 256 using the following scan parameters: 80 KVp, 120 mAc, total scan time 56 s, and slice thickness 5.0 mm. Intravenously, bolus was administered to all patients with 50 ml of ioversol 350 mg/ml, the rate of administration was 3.8–4.0 ml/s, the time from the moment of administration of the contrast medium to the start of scanning was 6 s. After receiving a series of images, the data was processed on a Philips workstation. Quantitative analysis was carried out according to the following indicators: TTP (time to peak, s), BV (blood volume, ml/100 g), AP (arterial perfusion, ml/min/100 ml), PP (portal perfusion, ml/min/100 ml), TP (total perfusion, ml/min/100 ml) and HPI (hepatic perfusion index, %).Results: In the control group of 8 patients, the perfusion values were: TTP 37.4±5.2 s, BV 16.1±5.0 ml/100 g, AP 25.0±7.5 ml/min/100 ml, PP 44.5±14.5 ml/min/100 ml, TP 70.1±14.9 ml/min/100 ml, HPI 70.1±14.9%. In 3 patients with F1, F2, according to the METAVIR conditional scale, the following statistically significant values (p

Aim.A comprehensive assessment of metabolic parameters in patients with non-alcoholic fatty liver disease and based on them the development of prognostic criteria for the development of liver fibrosis. Materials and methods.288 patients with non-alcoholic fatty liver disease at the stage of steatosis were examined. The patients underwent ultrasound examination of the hepatobiliary system using the SONIX OP apparatus (Canada), the FibroMax test, and liver elastography using the AIXPLORER apparatus (France). The parameters of anthropometry, lipid spectrum, protein and pigment metabolism, cytolysis, cholestasis, bilirubin, insulin in the blood serum were evaluated. The methods of statistical forecasting are used. Results.The clinical picture in patients with non-alcoholic fatty liver disease at the stage of steatosis was nonspecific and was due to the presence of concomitant diseases of the digestive system and the cardiovascular system. A kettle index of up to 30 was observed in 26.5% of patients, from 30 to 34.9 in 37.5%, from 35 to 39.9 in 29.7% of patients, more than 40 in 6.3% of patients. The results obtained during the biochemical analysis of blood serum indicate the presence of atherogenic dyslipidemia, an increase in the level of total protein, bilirubin, transaminases, gamma-glutamyl transpeptidase and a decrease in alkaline phosphatase in relation to the control group. Against the background of elevated glucose levels, an increase in basal insulin levels was observed (p=0.001). HOMA-IR insulin resistance was increased in patients (p=0.01). When analyzing the results of the study, the main prognostic criteria (body mass index and atherogenicity coefficient) in the diagnosis of non-alcoholic fatty liver disease in the stage of steatosis with high specificity (97.8%) and sensitivity (96.2%) were determined. In determining the risk of progression of non-alcoholic fatty liver disease into liver fibrosis, the model of prognostic criteria included insulin and triglycerides with a specificity of 93.8% and a sensitivity of 85.7%. Conclusion.Among many variable factors, we have identified the main prognostic criteria that are highly likely to diagnose non-alcoholic fatty liver disease at an early stage and determine the risk of progression to liver fibrosis.

The new American Association for the Study of Liver Diseases and Infectious Diseases Society of America recommendations for the management of hepatitis C patients are analyzed. To screen for viral hepatitis C, it is recommended that antibodies to the hepatitis C virus and RNA be detected in individuals with increased risk of infection. Patients with an increased risk of infection include people who inject narcotic drugs; patients with prolonged hemodialysis; health workers after contact with the blood or mucous membranes of a patient with viral hepatitis C; persons who received blood transfusions or blood components before 1987. In most patients, non-invasive tests can be used to diagnose liver fibrosis, which include physical examination, determination of serum fibrosis markers, including the FIB-4 index, ultrasound or computed tomography of the liver and liver elastography. The introduction of direct antiviral drug regimens significantly facilitated the treatment of viral hepatitis C and significantly increased the frequency of response to antiviral treatment. The development of combined pathogenetic regimens with a relatively short duration of treatment has become an important step in the management of patients with viral hepatitis C. New American recommendations suggest the use of pangenotypic regimens in patients with viral hepatitis C without fibrosis or with compensated liver cirrhosis: glecaprevir (300 mg)/pibrentasvir (120 mg) 3 pills per day within 8 weeks or the combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 1 pill per day for 12 weeks with the expected response to therapy in 95–100% of patients. Review authors note a number of rational aspects of the new American recommendations, but consider that experienced and qualified specialists should treat patients with chronic viral hepatitis C in Russia.

Aim. To evaluate the frequency of liver fibrosis progression to stage 34 among patients with non-alcoholic fatty liver disease (NAFLD), type 2 diabetes and obesity, to identify predictors of severe liver fibrosis, to propose an algorithm for diagnosing fibrosis in this category of patients. Materials and methods. 160 patients with NAFLD, type 2 diabetes mellitus (DM) and obesity and 50 patients with NAFLD without diabetes were comprehensively examined. Patients underwent laboratory examination (clinical blood test, biochemical analysis, immunoglobulins G, M, autoantibody assay, coagulogram), liver ultrasound. All patients underwent determination of the liver fibrosis stage by two methods: the serological test FibroMax and indirect ultrasound elastometry of the liver; 40 patients underwent a liver biopsy. Statistical data processing was performed using the programming language and statistical calculations R: we used correlation analysis, multiple logistic regression method, one-way analysis of variance, multi-factor analysis, the Kruskal-Wallis method, and comparison of the number of patients using the Fisher test. Results. DM is a risk factor for the liver fibrosis progression in patients with NAFLD. Significant markers of severe fibrosis in this category of patients are increased levels of GGTP, haptoglobin and alpha-2-macroglobulin, lower platelet and prothrombin levels. Obesity and isolated steatosis without steatohepatitis are not markers of severe liver fibrosis at present, but obesity can be considered a risk factor for the progression of fibrosis in the future. Conclusion. All patients with NAFLD in combination with diabetes need screening to detect advanced liver fibrosis: it is advisable to determine the levels of GGTP, haptoglobin and alpha-2-macroglobulin.

The growth hormone/insulin-like growth factor-1 (IGF-1) system is an important humoral mediator of liver function with an inherent potential for assessing liver condition and survival prognosis following liver transplantation (LT).Aim. Analysis of associations between growth hormone and IGF-1 levels in blood and markers of liver function and post-LT survival in children.Materials and methods. We examined 143 children with end-stage liver disease (ESLD) aged 3 to 73 (median 8) months after related LT. The growth hormone and IGF-1 concentrations in plasma were evaluated in ELISA assays. Results. In children with ESLD, concentrations of growth hormone and IGF-1 were significantly higher and lower, respectively, compared to healthy children of the same age (p

Fibrosis and cirrhosis are traditionally diagnosed by making a biopsy. However, in recent decades, scientists around the world have shown that the accepted “gold standard of diagnosis” – morphological assessment of biopsy – has a number of limitations. The search for non-invasive techniques to diagnose fibrosis has led to the development of many scales using laboratory indices. Non-invasive diagnostic techniques are safer for the patient than liver biopsy. In addition, they can be repeated in a dynamic to assess the condition of the liver over time. Most currently available non-invasive diagnostic techniques are considerably cheaper than the accepted “gold standard”. Their practical use is increasing every year, and in a number of countries the frequency of liver biopsies in viral hepatitis B and C is steadily decreasing due to the development of serum and imaging diagnostic systems. Recent studies show that the assessment of the degree of fibrosis by non-invasive methods is as accurate as a morphological study. In recent years, a number of serum markers have been considered as non-invasive diagnostics of the stages of liver fibrosis, among which the largest number of studies are devoted to hyaluronic acid, type IV collagen, and their combination with various common laboratory tests. The latest non-invasive techniques will make a significant paradigm shift in the evaluation of liver fibrosis in the near future. In this review we have analyzed widely used as well as experimental laboratory techniques used in the diagnosis of liver fibrosis.

Detection of liver fibrosis and steatosis at early stages is a difficult task for clinical practice, due to the lack of early signs in routine radiation diagnostics. Aim. To evaluate the efficacy of ultrasound shear elastography and ultrasound steatometry of the liver with the use of domestic ultrasonic diagnostic system Angiodin-Sono/N-Ultra. Materials and methods. 264 people held ultrasound elastography and ultrasound steatometry. 38 patients underwent percutaneous puncture liver biopsy and subsequent pathophysiological examination. Results. High correlation of fibrosis obtained at the Angiodin-Sono/N-Ultra and the leading ultrasonic systems with shear elastography was revealed. Cross-sectional comparative analysis of elasticity with the results of liver steatometry was conducted. Conclusions. Results obtained in all groups correlate with the data obtained in studies on Fibroscan. When working with system Angiodin we got a simultaneous comparative analysis of elasticity with the results of liver steatosis. Results appear to be much more stable and compact than those obtained in studies on the Fibroscan. A new diagnostic criterion was revealed the phenomenon of independence of fibrosis and steatosis indices.

The purpose of the study was to evaluate the fibroblast growth factor 21 levels (FGF-21) in blood plasma and the liver parenchyma state in non-alcoholic fatty liver disease (NAFLD) patients with hypertension. Materials and methods. 60 NAFLD patients aged 30 to 60 years were examined. The average age of the patients was (50.1 ± 6.9) years. The control group consisted of 20 practically healthy volunteers. All the patients were diagnosed with NAFLD, traditionally examined by clinical and laboratory methods, assessed for trophological status and lipid metabolism. The determination of FGF-21 was performed by the immune enzyme method in blood plasma using ELISA kits. Results. Evaluation of the liver parenchyma state demonstrated that in patients with NAFLD and hypertension, the F2-3 stage of fibrosis predominated in 60 % of cases. Depending on the existing stage of fibrosis, there was an increase in the liver enzymatic activity (P < 0.05, except the comparison results in patients with F0 and F1 stages), lipid profile (P < 0.001) and HOMA index (P < 0.05). An increase in the level of FGF-21 was detected in all NAFLD patients with hypertension and 3.4 times (P = 0.001) exceeded the parameters of practically healthy persons as well as its dependence on the stage of the liver fibrotic changes (P < 0.05, except the comparison results in patients with F1 and F2-3 stages). The correlations revealed confirm the pathogenetic relationship between FGF-21 and the liver inflammation development (P < 0.05). Conclusions. The FGF-21 levels in the blood plasma of NAFLD patients with hypertension exceed the parameters of the control group, are higher with increasing degree of liver fibrosis and associated with metabolic disorders in patients. The results obtained characterize the cytokine FGF-21 as a promising predictor marker for NAFLD progression.

Hepatitis B is an infectious viral disease in which damage or destruction of liver tissue occurs, and which can turn into a chronic form. In chronic hepatitis B (CHB), hepatocytes are replaced by connective tissue as they die, resulting in fibrosis, and then cirrhosis of the liver. Early diagnosis of liver fibrosis is an urgent task in the development of CHB. Already at this stage of the disease, the immune system is activated, which plays a leading role in liver damage in CHB. The main regulators of immune processes are cytokines, which mediate intercellular interactions. A separate group of cytokines are chemokines — proteins of cell migration. In CHB, they are responsible for infiltration of liver tissue by activated white blood cells. Cytokines and chemokines are active participants in fibrogenesis, so they can serve as biomarkers for the development of liver fibrosis, including in the early stages. The purpose of this study was to analyze the content of certain cytokines/chemokines in the peripheral blood of patients with CHB in order to search for potential biomarkers of the initial stages of liver fibrosis. The study included 30 patients with a confirmed diagnosis of CHB with stages of liver fibrosis F0-F1 on the Metavir scale, 36 patients with a diagnosis of chronic hepatitis C (F0-F1) and 37 conditionally healthy individuals as a control group. Concentrations of the following cytokines/chemokines were determined: IFNγ, TNFα, CCL2/MCP-1, CCL8/MCP-2, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, CXCL11/I-TAC by multiplex analysis using xMAP technology (Luminex, USA). As a result of the study, it was found that in patients with CHB, the plasma content of cytokine TNFα and chemokines CCL2/MCP-1, CXCL9/MIG and CXCL10/IP-10 was increased, and the chemokine CCL8/MCP-2 was reduced, which indicates the possibility of using these cytokines/chemokines as biomarkers of liver damage in CHB. In the examined group of patients with CHB, there was no dependence of the concentrations of cytokines and chemokines in the blood plasma on the viral load, which may be explained by its low level. For plasma cytokines in patients with CHB, correlations were found between TNFα and CCL2/MCP-1 and CCL8/MCP-2 chemokines , which was not observed in the control group. At the same time, in the control group, a correlation was found between the content of TNFα and the chemokine CXCL9/MIG, which was not detected in the group of patients. For both groups, a correlation was found between the content of CXCL9/MIG and CXCL10/IP-10 chemokines. Based on the study data, an algorithm has been developed that allows us to establish chronic hepatitis B or chronic hepatitis C as the cause of the initial form of fibrosis F0-F1 in terms of the content of cytokines IFNγ, CCL2/MCP-1 and CCL8/MCP-2 in blood plasma with a diagnostic efficiency of 89.4%.

Aim.Assessment of the diagnostic accuracy of predictive indexes of liver fibrosis for the identification of severe fibrosis and cirrhosis (F3F4) in patients with chronic hepatitis C (CHC). Materials and methods.The retrospective design study included 127 patients with chronic hepatitis C (mean age 44.511.1 years). To assess the degree of liver fibrosis, all patients underwent transient elastography using a Fibroscan (EchoSens, France) and predictive indexes of liver fibrosis were calculated (APRI, FIB-4, discriminant Bonacini score). Transient elastography was considered as a reference method for assessing the degree of liver fibrosis for subsequent comparison of results with predictive fibrosis indixes. Results.The sensitivity of the APRI index for the identification of severe fibrosis and cirrhosis of the liver (F3F4) was 79%, and specificity was 69%. The FIB-4 index showed greater specificity (86%), but less sensitivity (68%). The sensitivity of the discriminant Bonacini scale was 81%, and the specificity was 77%. The positive predictive value of the APRI index, FIB-4 and the Bonacini scale for the identification of severe fibrosis and cirrhosis of the liver (F3F4) in patients with chronic hepatitis C was 66; 78 and 72% respectively, and negative predictive value 82; 78 and 84% respectively. Conclusion.The results of this study indicate the relatively high diagnostic accuracy of a number of predictive indexes for evaluating liver fibrosis (APRI, FIB-4, discriminant Bonachini scale) in identifying severe fibrosis and cirrhosis of the liver (F3F4) in patients with chronic hepatitis C.

Objective: to study the differences in the frequency of pathological processes in liver biopsy samples of donors older than 60 years (group 1) and donors currently recognized as “standard” by age – 60 years and younger (group 2). Material and methods. Of the total pool of 300 consecutive donors with brain death, there were 28 (9.3%) donors over 60 years old (61 to 73 years old; 19 men and 9 women). Results. The frequency of pathology is independent of gender in both groups (p > 0.05). In elderly donors, compared with “standard” donors, mild (p < 0.05) and significantly more often severe (p < 0.05) albuminous degeneration are significantly less frequent, and there is only a tendency (p > 0.05) to more frequent mild hepatic steatosis. Dystrophic processes are the result of more severe ischemic injury to the liver of elderly donors. Ischemic liver injury determines the risk of more frequent biliary complications, which require careful monitoring and maintenance at an optimal level of hemodynamics for donors in the intensive care unit. Based on other morphological parameters, the liver of donors above 60 years of age does not significantly differ (p > 0.05) from the liver of donors 60 years and younger. Conclusion. To expand the donor pool, age restrictions should be removed when selecting a liver for transplantation, thereby maximizing the use of donor potential.

As a rule, chronic hepatitis C is manifested by the development of successive stages of liver fibrosis with the formation of eventually cirrhosis and liver cancer. However, in some patients the fibrosis progresses slowly, while in others there is a rapid formation of cirrhosis, which causes high mortality among such patients. According to published data, despite a fairly large number of studies regarding liver cirrhosis in chronic hepatitis C, factors contributing to liver fibrogenesis have not been definitively determined. The available data are quite contradictory. In this article, we review studies have assessed the TLR4 + 3725G/C gene polymorphism as a factor that may influence the rate of fibrotic progression. The research will build new approach for avoiding fast fibrogenesis.

The aim of the research – to optimize the prediction of hepatic fibrosis (HF) progression rate in HIV-infected patients with chronic hepatitis C (CHC) based on a comprehensive assessment of general clinical, biochemical, immunological and molecular-genetic markers. Materials and methods. A cross-sectional cohort study was conducted, which included 104 HIV-infected patients with CHC. The examination program included: assessment of complaints and anamnestic data obtained by questioning and detailed analysis of medical records, physical examination, general clinical study of peripheral blood, determination of biochemical parameters of blood serum, characterizing the functional state of the liver, the level of СD4+ Т-lymphocytes, the stages of HF according to METAVIR and genetic studies (genotyping of TLR7 in order to determine the carriage of Leu allele). Results. The method of discriminant analysis showed that statistically significant informative diagnostic signs of the rapid rate of HF progression in HIV-infected patients with CHC are: lymphocytosis, the levels of AST and total bilirubin exceeding the upper limit of normal, among the concomitant pathology ‒ chronic cholecystitis, chronic pancreatitis, cholelithiasis and hepatic steatosis, the baseline level of СD4+ Т-lymphocytes less than 350 cells/mm3 and a carriage of the normal genotype (Gln/Gln, Gln/-) of the TLR7 gene. In order to optimize the prognostication of the affiliation of an HIV-infected patient with CHC to the risk group of HF rapid progression there was proposed a discriminant model of 5 risk factors (the normal genotype (Gln/Gln, Gln/-) of the TLR7 gene, the levels of total bilirubin and AST exceeding the upper limit of normal, lymphocytosis, the baseline level of СD4+ Т-lymphocytes less than 350 cells/mm3), the exact prognosis of which was 75 %. Conclusions. There was proposed an effective model that allows predicting a rapid rate of HF progression in HIV-infected patients with CHC on the basis of simple characteristics, most of which are used in routine clinical practice.

The article presents modern views on morphological disturbances in liver tissue at HBV/HIV patients. It was shown that "matte-glass-like" hepatocytes, inflammatory cell lymphocytic infiltrate of varying degrees and liver fibrosis are specific signs of HBV/HIV patients. Specific morphological signs of liver damage in co-infected patients confirm that HIV-infection worsens histological structure as well as functional balance. Therefore, development of pathohistology method of diagnostics becomes more and more necessary in patients with complicated liver injuries. New findings can give opportunity for early screening HBV-infected patients for HIV-markers, prescribing antiviral treatment at early stages. The research will build new approach for avoiding fast fibrogenesis.

The problem of non-invasive monitoring of the liver condition is particularly relevant in liver transplantation among young children. Transforming growth factor beta 1 (TGF-β1) is a pleiotropic cytokine with a profibrogenic and immunosuppressive effect that can have a definite effect on the liver transplant functioning.Aim. To determine the diagnostic efficacy of TGF-β1 in blood when assessing the risk of developing graft dysfunction in liver recipient children. Materials and methods. 95 children aged 3 to 73 months with liver cirrhosis of various etiologies were surveyed. All the patients underwent liver transplantation (LT) from a living related donor. The TGF-β1 concentration in plasma was determined using ELISA on average 3 ± 2 days prior to liver transplantation and in the early post-transplant period.Results. The level of TGF-β1 in the blood of children with liver cirrhosis was lower than in healthy children (p = 0.001). LT was accompanied by an increase in the TGF-β1 content in the blood of recipients (p = 0.001). The incidence of graft dysfunction in the early postoperative period correlated with the pre-transplantation level of TGF-β1 (r = 0.40, p = 0.00), which was lower in recipients with developed graft dysfunction than in patients without dysfunction (1.7 ± 1.3 ng/ml versus 6.7 ± 5.3 ng/ml, p = 0.001). The analysis of the test diagnostic efficiency showed that the area under the ROC curve (AUC) was 0.85 ± 0.05, 95 % CI 0.75–0.94, the sensitivity of the method was 83 %, its specificity was 77 %. When the marker value was less than the threshold (2.2 ng/ml), the relative risk of developing graft dysfunction was 11.4 ± 0.7, 95 % CI 2.7-48.7. The accuracy of the method, the positive predictive value and the negative predictive value of the results were 78, 83 and 77 %, respectively. Conclusion. The level of TGF-β1 in the blood of liver recipient children before transplantation below 2.2 ng/ml increases the risk of developing graft dysfunction in the early postoperative period 11-fold. Measuring the TGF-β1 level in the blood prior to liver transplantation makes it possible to identify recipients with 85 % chance of developing a graft dysfunction.

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Current data on the molecular mechanisms of liver fibrosis and cirrhosis fail to fully explain all stages of their development. Interactions between individual genes and signaling pathways are known to play an important role in their functions. However, data on their relationships are insufficient and often contradictory. For the first time, mRNA expression of Notch1, Notch2, Yap1, Tweak (Tnfsf12), Fn14 (Tnfrsf12a), Ang, Vegfa, Cxcl12 (Sdf), Nos2, and Mmp-9 was studied in detail at several stages of thioacetamide-induced liver fibrosis in Wistar rats. A factor analysis isolated three factors, which combined highly correlated target genes. The first factor included four genes: Cxcl12 (r = 0.829, p < 0.05), Tweak (r = 0.841, p < 0.05), Notch1 (r = 0.848, p < 0.05), and Yap1 (r = 0.921, p < 0.05). The second factor described the correlation between Mmp-9 (r = 0.791, p < 0.05) and Notch2 (r = 0.836, p < 0.05). The third factor included Ang (r = 0.748, p < 0.05) and Vegfa (r = 0.679, p < 0.05). The Nos2 and Fn14 genes were not included in any of the factors. The gene grouping by mRNA expression levels made it possible to assume a pathogenetic relationship between their products in the development of fibrotic changes due to liver toxicity.

Aim. This study is aimed at evaluating the efficacy and safety of Bicyclol administration in patients suffering from non-alcoholic fatty liver disease (NAFLD) («ZIGUN» research) by monitoring laboratory data and non-invasive methods of diagnosis of liver fibrosis and steatosis.Materials and methods. The study included 93 patients with NAFLD with the average age of 44 (38–49) years, having the stage of liver fibrosis and steatosis greater than the 1st according to FibroScan (FibroScan 502 TOUCH with CAP software). Patients were randomized into 2 groups: 1) the main group comprised 67 patients receiving 75 mg/day of Bicyclol for 24 weeks in combination with aerobic exercise and Mediterranean diet; 2) the comparison group (26 patients) prescribed of only aerobic exercise and Mediterranean diet for 24 weeks.Results. During Bicyclol treatment, a decrease in the following indicators was observed: ALT, AST, GGT, CRP by 30 % or more, glycated hemoglobin (–10 %) and HOMA-index (–24 %), cholesterol (–12 %), LDL (–19 %), triglycerides (–31 %), atherogenic coefficient (–22 %). A decrease to the1st stage of fibrosis was observed in 30 patients (44 %), steatosis regression to the 1st stage was noted in 57 patients (85 %). Liver steatosis of the 4th stage was not revealed after treatment with Bicyclol. The number of patients with indolent steatosis (less than 2nd stage) increased 2 times (p < 0.001). No significant changes were found in the group without drug therapy.Conclusions. Bicyclol therapy in NAFLD is accompanied by positive dynamics of inflammation activity markers, insulin resistance and lipid spectrum, which suggests a positive dynamics of the stages of liver fibrosis and steatosis.

Aim - to develop the method of non-invasive determination of liver fibrosis in patients with chronic hepatitis С. Materials and methods. 446 patients with chronic HCV infection (aged from 18 to 65 years; male -52.3%; female - 47.7%) were comprehensively surveyed. The linear discriminant analysis with the exception of discriminatory variables used by the all registered laboratory and ultrasound indicators, as well as the age of patients was performed. The results of the survey of 223 patients were used to create the discriminant model and the results of a survey of the remaining 223 patients, were used for the testing of the accuracy of the received discrimination. Conclusion. The discriminant model for noninvasive determination of the degree of liver fibrosis in patients with chronic hepatitis C with high sensitivity - 88.0% and specificity is 96.2% is developed.

In this article we analyze contemporary scientific data on pathogenic, epidemiological and clinical aspects of nonalcoholic fatty liver disease (NAFLD) that has recently become the most prevalent liver pathology in Russia. The problem of comorbidity in patients with NAFLD is considered. The comparative analysis of invasive and non-invasive methods for diagnostics of liver fibrosis is given. The data on the prognostic value of liver fibrosis indices are summarized.

Rationale: Search for predictors of aggressive course of chronic hepatitis C virus (HCV) infection in individual patients, including genetic studies, is considered to be a major urgent goal. High rates of fibrosis progression in chronic HCV infection is associated with several gene polymorphisms coding for the components of renin-angiotensin system and involved in the formation of endothelial dysfunction and oxidative stress.Aim: To develop a predictive model to assess the probability of rapid fibrosis progression in patients with chronic HCV infection based on the combination of the known genetic markers, clinical and demographic parameters.Materials and methods: One hundred and nine patients with chronic HCV infection (79 women and 30 men) of known duration and liver fibrosis were categorized into the groups with “rapid fibrosis” (n = 54, the rate of fibrosis progression ≥ 0.13 fibrosis units / year) and with “slow fibrosis” (n = 55, the rate of progression < 0.13 fibrosis units / year). Polymorphisms of the studied genes were assessed by molecular genetic assays. Multivariate analysis of the influence of combination of genetic variants, as well as of the interaction of genetic, clinical and demographic factors on the rate of fibrosis progression in the patients with chronic HCV infection was performed by logistic regression method. Results: The rapid rate of fibrosis progression was significantly associated with patient's age at the time of infection (Wald statistics 14.955; p = 0.00011), male gender (Wald statistics 6.787; p = 0.00918), (-6)АА genotype of the AGT gene carriage (Wald statistics 6.512; p = 0.01072), 242ТТ-genotype of the CYBA gene (Wald statistics 4.347; p = 0.03708), and 235МТ genotype of the AGT gene (Wald statistics 4.306; p = 0.03799). The model to predict the probability of rapid fibrosis progression in individuals with chronic HCV infection included the above mentioned factors; its use was demonstrated with two clinical cases.Conclusion: The analysis of the AGT gene (M235T and G-6A loci) and the СYBA gene (C242T locus) polymorphisms are relevant to identify patients at risk of rapid liver fibrosis progression. In this case, 242ТТ genotype of the CYBA gene and (-6)AA and 235MT genotypes of the AGT gene are considered unfavorable. To refine the prognosis, it is necessary to take into account demographic parameters (gender and age at the moment of infection contraction), because male gender and older age of getting the infection would increase the probability of rapidly progressive of hepatitis C.

Aim. To determine whether there is a correlation of the composition of circulating lymphocyte subpopulations, the serum concentrations of interferon (IFN)-α, IFN-γ, and IFN-λ3, and the lymphocyte expression of types I and II IFN receptors with the species of a disease pathogen and the degree of liver fibrosis (LF) in patients with chronic hepatitis B (CHB) and in those with chronic hepatitis C (CHC). Subjects and methods. The investigation enrolled 44 patients with CHC, 9 patients with CHB, and 13 clinically healthy donors. The degree of LF in the patients was determined using transient elastography. The composition of peripheral blood lymphocyte subpopulations was examined; the concentrations of IFN-α, IFN-γ, and IL-28B were estimated. Results. Lymphocyte counts were higher in patients with CHC and in those with CHB than those in healthy donors; and the number of neutrophils was lower. There were no differences between the groups in the composition of lymphocyte subpopulations with the exception of the number of CD3CD4cells, which in patients with CHC was larger than in those with CHB. In CHC and CHB patients, the counts of CD118lymphocytes were higher than those in healthy donors. Patients with CHB and those with CHC did not differ between themselves and from healthy donors in the expression of CD119 on the lymphocytes. In CHC patients, the relative CD119cell counts were higher between CD4lymphocytes than those in healthy donors. The serum levels of IFN-α and IFN-γ in CHC and CHB patients were similar, but higher in healthy donors. The concentration of IL-28B genotype in patients with CHC was twice as high as in those with CHB, but the differences were statistically insignificant. The number of lymphocytes increased with the progression of fibrosis; that of neutrophils decreased. There was an inverse relationship between platelet counts and LF severity. Multiple comparisons of the clusters of patients with different degrees of LF revealed no differences in the number of major lymphocyte subpopulations. However, the number of CD3CD16CD56natural killer-like T (NKT) cells correlated with fibrosis severity. Patients with different degrees of LF showed no differences in the proportion of CD118and CD119 cells between lymphocytes and in the serum levels of IFN-α, IFN-γ, and IL-28B levels. Patients with grade IV LF displayed a higher proportion of CD4CD119lymphocytes between CD45cells than did those with grade III LF. Conclusion. Several new clinical and laboratory trends were identified and the nature and extent of previously described hematological and immunological changes were clarified in CHC or CHB patients with various degrees of LF. Some indicators may be used as additional criteria for the prognosis of the above forms of hepatitis, and a number of newly described facts suggest that it is necessary to revise the protective/phlogogenic value of types I, II, and III IFNs in chronic viral hepatitis C and B.

The aim. To assess the influence of liver fibrosis stage on the clinical course of periodontal diseases in patients with chronic hepatitis C. Material and Methods. 122 patients with chronic hepatitis C, treated at the 7th department ofLvivRegionalInfectiousDiseasesHospital during 2013 – 2015 were included into dental investigation. The periodontal disease was diagnosed in accordance with the classification of M. F. Danilevsky (1994). The clinical condition of periodontium was assessed by the papillary marginal alveolar index (PMA) in the modification ofParma, by the periodontal index – PI (AL Russel, 1956), by the Muhlemann and Son index – the degree of bleeding in the region of the gingival papilla (PBI). The stage of liver fibrosis was determined according to the medical history. The significance of the difference between two or more relative indicators was calculated using the Fisher test with the Metropolis algorithm. The correlation dependence between the clinical condition of periodontal tissues and the stage of liver fibrosis in patients with viral hepatitis C was studied using the Spearman rank correlation coefficient. Results. The highest percentage of patients with stage of liver fibrosis F0 (70.00 ± 15.28 %) was registered in patients with healthy periodont, the lowest - in patients with generalized periodontitis of the third stage (7.89 ± 4.37 %). The highest frequency of patients with the stage of liver fibrosis F3 (73.68 ± 7.14 %) was also observed in persons suffering from generalized periodontitis stage III (73.68 ± 7.14 %). Conclusions. The distribution of periodontal lesion severity statistically significant (p < 0.001) depended on the stage of liver fibrosis in patients with chronic hepatitis C. Direct (R = 0.70; p < 0.001) strong correlation between the clinical state of periodontal tissues and the stage of liver fibrosis in patients with chronic hepatitis C (using the Spearman rank correlation coefficient) has been determined

The aim of this work is to investigate the direct markers of liver fibrosis (LF) in patients with steatohepatitis non-alcoholic and alcoholic origin in combination with obesity (OB) and pathology of the biliary tract (BT). Materials and Methods. We examined 30 patients with steatohepatitis of different etiology, in 15 patients of them was non-alcoholic steatohepatitis (NASH) and 15 had alcoholic steatohepatitis (ASH). The control group consisted of 15 practically healthy persons (PHP). Direct markers of fibrosis – matrix metalloproteinase-1 (MMP-1), laminin (LN), hepatocyte growth factor (HGF) were determined by ELISA. Results. In all groups of patients we found a significant decrease in MMP-1 1.7 times in NASH (p < 0.001) and 1.6 times at ASH in comparison with the reference values of PHP (p < 0.05). It has been defined the increase in the content of LN 1.8 times in the NASH group in relation to PHP (p < 0.001). A high level of LN was observed in the group of ASH and increased in 2.2 times compared with PHP (p < 0.001) and 1.2 times compared with NASH patients (p < 0.001). The content of HGF was reduced compared with control 1.5-fold and 1.6-fold respectively, in NASH and ASH (p < 0.001 for all comparisons). Conclusions. It has been established that reduced levels of MMP-1 and increased levels of LN indicated the progression of LF in patients with steatohepatitis with more pronounced progression during the ASH. It has been proved that the elevated level of LN and reduced level of HGF, coupled with the presence of non-alcoholic or alcoholic factor, had made a significant contribution to the development of LF in patients with NASH and ASH in combination with theOB and pathology of BT.