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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.

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.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.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.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.Цель. Оценить частоту прогрессирования фиброза печени до стадий 34 среди больных неалкогольной жировой болезнью печени (НАЖБП), сахарным диабетом (СД) 2-го типа и ожирением, выявить предикторы формирования тяжелого фиброза печени, предложить алгоритм диагностики фиброза у данной категории больных. Материалы и методы. Комплексно обследованы 160 пациентов с НАЖБП, СД 2-го типа и ожирением и 50 больных НАЖБП без СД. Больным выполнялись лабораторное обследование (клинический анализ крови, биохимический анализ, иммуноглобулины G, M, исследование аутоантител, коагулограмма), ультразвуковое исследование печени. Всем пациентам проводилось определение стадии фиброза печени двумя методами: серологический тест ФиброМакс и непрямая ультразвуковая эластометрия печени; 40 пациентам выполнена пункционная биопсия печени. Статистическая обработка данных проводилась с использованием языка программирования и статистических вычислений R: использовались корреляционный анализ, метод множественной логистической регрессии, однофакторный дисперсионный анализ, многофакторный анализ, сравнение показателей между группами методом КраскелаУоллиса, сравнение числа пациентов с помощью теста Фишера. Результаты. СД является фактором риска прогрессирования фиброза печени у больных НАЖБП. Значимые маркеры выраженного фиброза печени у данной категории больных повышение уровней g-глутамилтранспептидазы (ГГТП), гаптоглобина и альфа-2-макроглобулина, более низкие уровни тромбоцитов и протромбина. Ожирение и изолированный стеатоз без стеатогепатита не являются маркерами тяжелого фиброза печени в настоящее время, однако ожирение можно считать фактором риска прогрессирования фиброза в будущем. Заключение. Все больные НАЖБП в сочетании с СД нуждаются в скрининге с целью выявления продвинутого фиброза печени: целесообразно проводить определение уровней ГГТП, гаптоглобина и альфа-2-макроглобулина.

To determine the diagnostic value of clinical features of the comorbid course of non-alcoholic fatty liver disease (NAFLD) and gallstone disease (GD) to improve the effectiveness of patient management.183 patients with NAFLD were included into the open comparative study. The main group was represented by patients with NAFLD and GD (n=88), of which 53 patients underwent cholecystectomy (CE). The comparison group was represented by patients with NAFLD without GD (n=95). A standard laboratory and instrumental examinations were performed, including elastometry to assess of the stage of liver fibrosis.There were more women in the main group (2=8.48; p0.01). There were positive correlations between the age of patients and the duration of NAFLD with the presence of GD and CE (rs=0.135; p0.01 and rs=0.168; p0.01 respectively). Patients of the main group had the general weakness and fatigue (2=11.33, rs=0.234; p0.01 and 2=15.68, rs=0.281; p0.01 respectively), as well as a bitter taste in the mouth (2=11.66; p0.01; rs=0.147; p0.01). Coronary heart disease was diagnosed more often among people suffering from NAFLD and GD (25% vs 9.47% in patients of the comparison group, p0.01). Both of NAFLD and GD were associated with the development of type 2 diabetes (rs=0.164; p0.01). Individuals suffering from GD after CE had higher LDL and GGT values (rs=0.228; p0.01 and rs=0.298; p0.01 respectively). The number of people with advanced fibrosis were significantly higher (26.31%) in the GD group, especially among people after CE (30.18%). The stage of liver fibrosis had a positive significant relationship with CE (rs=0.366; p0.01).Patients suffering from GD and NAFLD had a symptom of dyspepsia and general weakness. High prevalence of type 2 diabetes and сoronary heart disease, high level of LDL and GGT were found in patients with GD and after CE. CE in patients suffering from GD and NAFLD was associated with the formation of progressive stages of liver fibrosis.Цель. Для повышения эффективности ведения пациентов определить диагностическую ценность клинических особенностей коморбидного течения неалкогольной жировой болезни печени (НАЖБП) и желчнокаменной болезни (ЖКБ). Материалы и методы. В открытое сравнительное исследование включены 183 пациента с НАЖБП. Основная группа представлена пациентами с НАЖБП и ЖКБ (n=88), из которых 53 перенесли холецистэктомию (ХЭ), группа сравнения пациенты с НАЖБП без ЖКБ (n=95). Проведено стандартное лабораторно-инструментальное обследование, в том числе оценка стадии фиброза печени с помощью эластометрии. Результаты. В основной группе женщин статистически достоверно больше (2=8,48; p0,01). Имелись положительные корреляционные взаимосвязи возраста пациентов, длительности течения НАЖБП с наличием ЖКБ и ХЭ (rs=0,135; p0,01 и rs=0,168; p0,01 соответственно). Общая слабость и быстрая утомляемость более часто встречались у пациентов основной группы (2=11,33, rs=0,234; р0,01 и 2=15,68, rs=0,281; р0,01 соответственно), а также ощущение горечи во рту (2=11,66; р0,01; rs=0,147; р0,01). Среди лиц, страдающих НАЖБП и ЖКБ, чаще диагностирована ишемическая болезнь сердца (25% против 9,47% у пациентов группы сравнения; р0,01). Сочетание НАЖБП и ЖКБ ассоциировано с развитием сахарного диабета 2-го типа (rs=0,164; р0,01). У лиц с сопутствующей ЖКБ и перенесенной ХЭ отмечаются более высокие показатели липопротеидов низкой плотности и -глутамилтранспептидазы (rs=0,228; р0,01 и rs=0,298; р0,01 соответственно). Достоверно выше число лиц с прогрессирующими стадиями фиброза в группе ЖКБ (26,31%), особенно у лиц после ХЭ (30,18%). Стадия фиброза печени имела положительную достоверно значимую взаимосвязь с ХЭ (rs=0,366; р0,01). Заключение. Коморбидное течение ЖКБ и НАЖБП клинически характеризуется симптомами диспепсии и общесоматическими жалобами. У пациентов с ЖКБ и перенесенной ХЭ установлена высокая распространенность сахарного диабета 2-го типа и ишемической болезни сердца, отмечаются более высокие показатели липопротеидов низкой плотности и -глутамилтранспептидазы. Перенесенная ХЭ у пациентов, страдающих ЖКБ и НАЖБП, ассоциирована с формированием прогрессирующих стадий фиброза печени.

To update information about comorbidity of non-alcoholic fatty liver disease (NAFLD) and gallstones disease (GD), evaluation of clinical and laboratory data, including insulin, leptin and adiponectin in individuals with NAFLD in combination with GD.According to the design, we conducted an open comparative study of 169 patients with NAFLD. The following comparison groups were formed: group 1 (n=95) patients with NAFLD without GD, group 2 (n=35) patients with NAFLD and GD and group 3 (n=39) patients with NAFLD, GD and previous cholecystectomy.A high prevalence of coronary heart disease was found in the group of patients with GD and cholecystectomy (2=6.198,p0.05); positive, statistically significant correlation relationships of cholelithiasis, cholecystectomy with ischemic heart disease (rs=0.172,p0.05 andrs=0.241,p0.05, respectively). There was a statistically significant decrease in total bilirubin and total protein in patients of group 3 (H=7.376,p0.03 and H=6.345,p0.04). The level of leptin is statistically significantly higher and positively interrelated with cholecystectomy (H=5.812,p0.05,rs=0.313,p0.05).Patients with NAFLD, GD and previous cholecystectomy have a high prevalence of coronary heart disease; the phenomenon of insulin and leptin resistance, high level of adiponectin were revealed in patients with NAFLD and gallstones; hyperleptinemia was observed among patients with NAFLD, GD after cholecystectomy.Цель исследования.Актуализация информации о коморбидности неалкогольной жировой болезни печени (НАЖБП) и желчнокаменной болезни (ЖКБ), оценка клинических, лабораторных данных, в том числе уровней инсулина, лептина и адипонектина, у лиц с НАЖБП в сочетании с ЖКБ. Материалы и методы.Согласно дизайну нами проведено открытое сравнительное исследование с включением 169 пациентов с НАЖБП. Сформированы следующие группы сравнения: группа 1 (n=95) пациенты с НАЖБП без ЖКБ, группа 2 (n=35) пациенты с НАЖБП и ЖКБ с сохраненным желчным пузырем и группа 3 (n=39) пациенты с НАЖБП и ЖКБ, перенесшие холецистэктомию. Результаты.Выявлена высокая распространенность ишемической болезни сердца (ИБС) в группе пациентов с ЖКБ, перенесших холецистэктомию (2=6,198;p0,05), обнаружены положительные статистически значимые корреляционные взаимосвязи ЖКБ, перенесенной холецистэктомии с ИБС (rs=0,172,p0,05 иrs=0,241,p0,05, соответственно). Отмечалось статистически значимое снижение уровня общего билирубина и общего белка у пациентов 3-й группы (H=7,376,p0,03 и H=6,345,p0,04). Уровень лептина статистически значимо выше и положительно взаимосвязан с холецистэктомией по результатам сравнительного и корреляционного анализа (H=5,812,p0,05,rs=0,313,p0,05). Заключение.Пациенты с НАЖБП, ЖКБ и перенесенной холецистэктомией имеют высокую распространенность ИБС; у пациентов, страдающих НАЖБП и ЖКБ, выявлен феномен инсулино- и лептинорезистентности, высокий уровень адипонектина; гиперлептинемия отмечена среди больных НАЖБП с ЖКБ после холецистэктомии.

Objective. To evaluate the effectiveness of the ultrasound steatometry technique in patients with non-alcoholic fatty liver disease. Materials and methods. 68 patients aged 19–62 years (median age 40.5 years) were examined, 30 men (44.1%) and 38 women (55.9%), who underwent a single diagnostic algorithm of 7 (8) stages: questioning, clinical examination, noninvasive bioimpedance, biochemical blood test, liver ultrasound in B-mode, determination of hepatorenal index, ultrasound steatometry, liver biopsy. Results. In 4 patients (5.88%), a remote clinical picture of the metabolic syndrome, fatty liver infiltration was diagnosed. Signs of steatohepatitis were present in 19 (27.9%) patients, signs of cirrhosis — in 2 (2.9%). The sensitivity and specificity were 60.3% and 72.6%, respectively, for the B-mode, 44.3% and 51.9%, respectively, for the ultrasound measurement of the hepatorenal index, 90.6% and 92.2%, respectively, for ultrasonic steatometry. Conclusion. Ultrasound steatometry is an informative method for screening of patients with non-alcoholic fatty liver disease. Correlation (r) of the ultrasound diagnosis of steatosis with biopsy at the stage S0 corresponds to 0.81, at the stage S1 — to 0.68, at the stage S2 — to 0.74, at the stage S3 — to 0.88, that indicates a high information value of this method.

Aim. To evaluate effects of ursodeoxycholic acid (UDCA) on inflammation, steatosis and liver fibrosis and atherogenesis factors in patients with non-alcoholic fatty liver disease (NAFLD). Materials and methods. The study included 139 patients with NAFLD who received 15 mg/kg of UDCA (Ursosan ® ) per day for 24 weeks. Before and after the study, liver function and lipid metabolism, liver steatosis index FLI, intimamedia thickness (IMT) of the carotid arteries were determined. The cardiovascular risk was calculated according to the ASCVD 2013. Results. The use of UDCA in patients with NAFLD led to a decrease in ALT ( p < 0.001), AST ( p < 0.001) and GGT ( p < 0.001) activity; total cholesterol concentration ( p < 0.001); triglycerides ( p < 0.001); and LDL ( p < 0.001) in the blood and the FLI liver steatosis index ( p < 0.001). In addition, the rate of cardiovascular risk (p = 0.022) and IMT (р = 0.048) in women also decreased. Conclusions . The use of UDCA in NAFLD reduces the activity of inflammatory processes in the liver, its steatosis, and also improves lipid metabolism and exerts potential anti-atherogenic effects. Against the background of UDCA administration, there was no progression of liver fibrosis. None of the participants in the observational programme reached a normal body mass by the end of the program; therefore, the attained positive changes should be attributed directly to the effects of UDCA.

Aim.In this research, we set out to study organic changes in the heart and blood vessels of obese men suffering from non-alcoholic fatty liver disease (NAFLD) combined with cardiac pathology in the metabolically unhealthy phenotype (MUHP). Another objective consisted in establishing a relationship between liver damage and the pathology of the heart and blood vessels.Materials and methods.A group of 112 men (male)aged 61.2±1.7 diagnosed with the ischemic heart disease (IHD) and stage 1–3 arterial hypertension (AH) were examined during the stationary treatment in the Republican Clinical Diagnostic Centre (Izhevsk, Russia). The patients were divided into 3 groups according to their body mass index (BMI): 29 men with a BMI under 25 kg/m2(I group); 43 overweight men a BMI over 25 of kg/m2(II group); 40 men with obesity and a BMI above 30 of kg/m2(III group). Laboratory and non-invasive instrumental examinations required for the diagnostics of NAFLD and IHD were carried out, including liver ultrasound and FibroScan elastometry. Other examinations included the measurement of the intra-abdominal adipose tissue (IAT) and epicardial adipose tissue (EAT) thickness, the calculation of the visceral adiposity index (VAI), the estimation of endothelial dysfunction indicators, as well as the assessment of the structural and functional parameters of the heart and blood vessels.Results.In obese patients with pronounced NAFLD signs, IAT, EAT and VAI indicators are shown to increase in direct correlation with the parameters of liver steatosis. A relationship is established between the most significant structural and functional indicators of the heart (myocardial mass index, volume of the left atrium), blood vessels (endotheliumdependent vasodilation, the size of the intima-media complex of the common carotid artery) and NAFLD. It is demonstrated that the correlation coefficients grow with the progression of fatty infiltration and liver fibrosis signs.Conclusions.The results of the study have revealeda connection between the NAFLD presence and the main markers of visceral fat depots (IAT, EAT, VAI), which is shown to increase the risk of cardio-vascular complications in such patients. NAFLD is accompanied by endothelial dysfunction and a change in the most significant parameters of cardiac and vascular remodelling. These parameters manifest the progression of pathological changes in the liver parenchyma, which increases the cardio-metabolic risk in patients with MUHP.

Aim. The aim of the review is to present current data on the relationship between non-alcoholic fatty liver disease (NAFLD) with the metabolic disorders of bile acids (BA) and changes in the composition of the intestinal microbiota.Background. NAFLD is accompanied by a change in the intestinal microbiotic composition: the proportion of taxa deconjugating BAs increases, while the proportion of taxa converting primary BAs to secondary ones decreases. The number of bacteria forming lipopolysaccharide (LPS) also increases. LPS, entering the liver with the portal vein blood, promotes the development of its inflammation and insulin resistance. The disturbance of bile acid metabolism through the effect on the FXR and TGR5 receptors also leads to insulin resistance and liver steatosis. FXR probiotics and agonists are promising drugs for the NAFLD treatment.Conclusion. In the course of NAFLD, a change in the composition of the intestinal microbiota is observed, which contributes to the development of inflammation in the liver and disrupts the metabolism of bile acids, leading to insulin resistance.

Non-alcoholic fatty liver disease (NAFLD) becomes gradually the most frequent liver disease in the world. Expert teams in the USA, Western Europe, and Russia give pride of place within the NAFLD treatment regime to lifestyle modification including the optimization of physical activity, diet and, as a consequence, the BMI reduction. However, it is often difficult for the practitioner to motivate the patients to change their lifestyle and eating habits. Due to this, it is extremely important to use a pharmacologic therapy aimed at weight loss, reducing insulin resistance and repopulating the severely damaged liver parenchyma. By now ursodeoxycholic acid drugs (Ursosan) have been proved to be highly effective in treating NAFLD in clinical practice, having a significant impact on several pathogenetic mechanisms of this disease.

Sodium-glucose cotransporter-2 inhibitors are the new drugs for the treatment of type 2 diabetes mellitus. Its mechanism of action is to increase the excretion of glucose in the urine due to inhibition of reabsorption in the proximal renal tubules, which leads to a decrease in blood glucose levels. These drugs also have pleiotropic effects including reduce body weight and blood pressure, improve the lipid profile (raising high-density lipoprotein cholesterol and lowering triglyceride levels), and reduce the risk of cardiovascular death and nephroprotection. Ipragliflozin, a new representative of the class of sodium glucose cotransporter-2 inhibitors, registered in Russia, has shown effectiveness in relation to glycemic control, reducing the levels of glycated hemoglobin and fasting plasma glucose both in monotherapy and in combination with other antihyperglycemic drugs. The PRIME-V and ILLUMINATE studies have demonstrated that ipragliflozin helps to reduce insulin resistance, body weight, BMI and waist circumference, total and LDL cholesterol. Positive effects of ipragliflozin on pancreatic β-cell mass and function have been shown in animal studies. Several studies have examined the beneficial effects of ipragliflozin on the course of non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus. Significant reductions in ALT and GGT levels and a decrease in the absolute percentage of liver fat have been shown. Animal studies have confirmed the effect of ipragliflozin on the histological characteristics of NASH. The review presents data on the efficacy of ipragliflozin in relation to the components of the metabolic syndrome in patients with type 2 diabetes mellitus, and also discusses the likely mechanisms of a positive effect of the drug on the course of NASH in type 2 diabetes mellitus.

According to the World Health Organization estimates, non-alcoholic fatty liver disease (NAFLD) will be ranked number one in the liver diseases pattern by 2020. Liver transplantation in patients with cirrhosis as the outcome of NAFLD currently ranks next to the viral liver cirrhosis. According to current concepts, NAFLD is a liver disease defined as fatty dystrophy, fatty degeneration with inflammation and possible outcome in cirrhosis. The causal relationship between NAFLD and diabetes mellitus is the subject of numerous discussions. Insulin resistance is the binding pathogenetic link between one and the other disease. First of all, insulin resistance is carried out at the level of hepatocyte. Until now, there is no standard therapy for NAFLD. Correction of body weight, changes in food addiction, physical activity is the most effective measures to prevent the development of NAFLD and diabetes mellitus. None of the drugs used for the treatment of NAFLD has evidence base for the effect on the histological pattern of NAFLD.

Aim. To investigate on the efficacy of thiotriazoline (TTZ) in complex management of acute myocardial infarction (AMI) patients with hepatic steatosis. Material and methods. Totally, 32 left ventricle AMI patients included, comorbid with non-alcoholic fatty liver disease. Assessment of electrical activity of myocardium was done on improved polygraph with electroand vectorcardiogram registration before and post three week basic therapy in 16 patients (13 males and 3 females, mean age — 60,5±3,74 y.o.) and management with added TTZ (8 males and 8 females, mean age – 62,94±2,71 y.o.). Results. On basic therapy, there was ongoing decline in electromotive force of the heart with slower impulse conduction and disordered repolarization in atrial myocardium, with decreasing area of damage in the left ventricle and atrial overload. Concomitant TTZ usage with basic therapy led to minimal positive shifts in electromotive force of the heart. Also, there was increase of ischemia zone due to decrease of myocardial damage area, more prominent normalization of left atrium compartment and stabilization of repolarization processes in atria. Conclusion. Under the combination treatment by TTZ there was significant change of the grade of electrical activity of the heart electrical activity disorder comparing to basic therapy.

The rapidly growing incidence of obesity and diabetes mellitus, especially in developed countries, stimulates medical experts to closely study the epidemiology of non-alcoholic fatty liver disease (NAFLD). According to the published results of the epidemiological study DIREG 2, the prevalence of NAFLD in outpatients inRussiaincreased over the period from 2007 to 2015 and amounted to 37.3%. In the present report, the population of patients with NAFLD in the Far East Federal District (FEFD) was studied as part of the multicentre epidemiological study DIREG 2. The aim. To analyze the data on FEFD obtained in the DIREG 2 study and compare those with the DIREG 2 data on the entireRussia. Materials and Methods . The prospective disease registry study: epidemiological, observational, cross-sectional, multicentre study on the prevalence of NAFLD in outpatients. The total number of participating patients in FEFD was 2500, including 900 males and 1600 females. Epidemiological data were collected within two routine patient visits to the participating research centers. Results . The major result of this study is that the prevalence of NAFLD in FEFD was significantly lower than that in the entireRussia (21.4% vs 37.3%). Although the rank distribution of the concomitant diseases in FEFD patients was comparable to that in the across-Russia population, the prevalence of metabolic syndrome, menopausal syndrome and hypertriglyceridemia was significantly higher in the FEFD population. Conclusion . Despite the lower prevalence of NAFLD there is a significantly higher prevalence of disorders associated with NAFLD in the FEFD patients as compared with the acrossRussian patients from DIREG2. A set of measures preventing these risk factors from converting into full-scale disease is needed.

The aim of the research was to study the biochemical model of morphological changes in the liver of patients with different forms of non-alcoholic fatty liver disease NAFLd, overweight and abdominal obesity (AO). Morphological changes in liver tissue were determined by non-invasive method Ste- atoskreen . The study evaluated the relationship between the cytolytic syndrome, forms of NAFLd and various manifestations of metabolic syndrome (MS). According to the survey, morphologically NAFLd was confirmed in 98% of patients using non-invasive diagnostic test Steatoskreen . The progression of different forms of NAFLd was significantly correlated with various metabolic disorders (dyslipidemia, impaired glucose metabolism, insulin resistance, obese) increases with the progression of NAFLd.

Combined liver damage in patients with chronic heart failure and non-alcoholic fatty liver disease leads to the formation of pathological hemodynamic types of microcirculation with prevalence of shunt blood flow, nutritional deficiency, that correlated with changes in the functional state of the liver. Using cytoprotector mexicor for 16 weeks as part of the basic treatment of patients with chronic heart failure and non-alcoholic fatty liver disease can correct these microcirculatory disorders, has a beneficial effect on endothelial function, autonomic tone of microvessels, which is accompanied by the positive dynamics of indicators of cytolysis and cholestasis.

Diagnosis of liver disease in particular non-alcoholic fatty liver disease (NAFLD) is largely determined by methods that are informative, safe, non-invasive, highly sensitive and can be used in all patients without exception. One of these methods is gas chromatography-mass spectrometry (GC-MS). Our study presents the results of serum metabolome assessment by the GC-MS method in male patients for the diagnosis of NAFLD at the stage of non-alcoholic steatohepatitis. In serum samples obtained from 25 patients, 319 compounds were identified, among them 109 were annotated. In patients with NAFLD, there was a significant increase in indole carboxylic and fatty acids, hypoxanthine, hydroxycarboxylic and phenylcarboxylic acids. The results of the study showed that low-molecular metabolites in particular reduced levels of 4-hydroxybutyric acid and 360 compounds suggests possible influence of metabolites on the pathogenesis of NAFLD, and an elevated level of sugar alcohol suggests a possible damaging effect on liver cells. For the detected compounds 4-hydroxybutyric acid, compound-360 and sugar alcohol, high specificity and sensitivity values, high confidence intervals and AUC values were shown, which indicates the possibility of using mass spectrometry analysis of plasma metabolome at high levels of steatohepatitis with high degree of reliability and probability.

Aim. To create a model for non-alcoholic fatty liver disease (NAFLD) development at the steatosis stage in visceral obesity in patients with coronary artery disease (CAD) and hypertension (HTN).Material and methods. The study included male patients with coronary artery disease, stable angina and hypertension: experimental group — 75 patients, control group — 38 patients. All patients underwent an anthropometric assessment, visualization and measurement of the intraabdominal fat thickness (AIFT) and epicardial fat thickness (EFT) by ultrasound, and echocardiography. The liver state was assessed using clinical and functional biochemical tests and ultrasound. Lipid and carbohydrate metabolism parameters was also evaluated. The influence of each of the studied indicators on NAFLD development was determined using the factor and correlation analysis.Results. We created a mathematical model for predicting the NAFLD at the steatosis stage. Using significant variables (body mass index (BMI), EFT, AIFT, left ventricular posterior wall thickness (LVPWT), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) value), a regression model was created. There was following resulting regression equation: prognostic index K= -24,9+0,81 хBMI+1,06хEFT+0,02хAIGT+0,6хLVPWT-1,07хHOMA-IR. To test the developed model, a double-blind randomized study was performed. At K15,38 — as high. Values from 9,37 to 15,38 are considered intermediate.Conclusion. During the study, an original model was developed to calculate the likelihood of NAFLD development. The resulting model with the assessment of risk factors in patients with CAN and HTN with visceral obesity can be used to plan a prevention strategy. Patented invention №2718325RU dated 01.04.2020.

The objective of the study was to evaluate the effect of bariatric operations on the course of nonalcoholic fatty liver disease (NAFLD) and determine the possibility of using non-invasive diagnostic methods for NAFLD.Material and methods. The published data review of the NAFLD dynamics after bariatric surgery.Results. Currently there is no common opinion on the effectiveness and safety of bariatric operations in NAFLD treatment.Conclusion. Further research and randomized controlled clinical study are needed.

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 of review. To consider different treatment options for dyslipidemia in non-alcoholic fatty liver disease (NAFLD). Summary. NAFLD occurs in 20-30% of adult population. In the Russian Federation its rate is estimated as high as 37,1%. In the most of NAFLD cases severe disorder of lipid metabolism takes place. In large clinical trials it was demonstrated that the dyslipidemia significantly increases cardiovascular risks and worsens life expectancy in these patients. In the present overview treatment options of several therapeutic agents for dyslipidemia treatment at NAFLD are discussed: phenofibrate, omega-3 polyunsaturated fatty acids (omega-3-PUFAs) and S-adenosylmethionine (SAM). Results of numerous experiments and several clinical trials form the basis for phenofibrate administration for NAFLD patients. In animal experiments the positive role of phenofibrate as PPARα agonist was demonstrated (Peroxisome proliferator activated receptor alpha) for NAFLD prevention and treatment. Results of several studies published at the moment demonstrate that at NAFLD lipid metabolism markers, and serum transaminase levels normalize, sensitivity to insulin increases, the liver histology pattern improves at phenofibrate treatment. Specification of efficacy and safety of application of the drug requires more large-scale clinical studies. Omega-3-PUFAs is one more option in the lipid metabolism disorders treatment in this group of patients. These substances play important role in lipid metabolism regulating expression of the genes (including PPARα) involved in lipid and glucose metabolism. Available clinical trials demonstrate high therapeutical effect of these agents at NAFLD. In the review results of the experimental studies investigating the role of SAM in NAFLD pathogenesis and disorders of lipid metabolism is presented. Conclusion. Now data on a pathogenesis of lipid metabolism disorders at NAFLD are accumulated. The bulk of experimental data and series of clinical trials allow to assume positive affect of such drugs as phenofibrate, omega-3-PUFA and SAMe for treatment of dyslipidemia. Further high-grade studies in this area is necessary.

Aim of investigation. To study the vascular wall changes of common carotid artery and internal carotid arteries in patients with abdominal obesity (AO) and different forms of nonalcoholic fatty liver disease (NAFLD). Material and methods. The study involved 60 patients with AO (waist circumference ≥80 cm in women and ≥94 cm in men) and NAFLD who provided written informed consent to participate in the study. The age of the patient ranged from 18 to 59 years. Patients’ symptoms, past history, were evaluated to exclude alcoholic or drug-induced liver disease, anthropometric parameters were studied. All patients underwent a complex of laboratory and instrumental tests required by the Russian guidelines for diagnosis and treatment of NAFLD (2015). Severity of pathological changes in the liver tissue (fibrosis and steatosis) was assessed by noninvasive Steatoskrin diagnostic method (Biopredictive laboratory, France). Measurement of the intima-media complex thickness of the common carotid artery (IMT CCA) was performed by standard procedures at Voluson 730 Expert device, equipped with 7,5 MHz linear phased array transducer. The presence of early atherosclerotic markers was evaluated by local thickening of the IMT CCA over 0.86 mm in any point of the carotid artery (IMT CCA max). The data were processed by comparative and correlation analysis. Results. The relationship between the presence of NAFLD, initial manifestations of atherosclerosis and insulin resistance was established. This resulted in the rank of prognostic factors based on severity of carotid artery changes, making it possible to conclude individual atherosclerotic risk score for AD and different forms of NAFLD. Conclusion. The results of the study require more profound examination of patients with NAFLD to evaluate both liver and cardiovascular diseases risk.

Nonalcoholic fatty liver disease (NAFLD) – a common chronic disease of the liver, the main feature of which is the accumulation of fat in hepatocytes, is not related to alcohol abuse. NAFLD is associated with obesity, especially abdominal, metabolic syndrome and various metabolic markers of risk for cardiovascular disease and type 2 diabetes, which affects the incidence, prognosis and life expectancy of patients with obesity. This lecture describes the main causes of the disease, its pathogenesis, clinical presentation, diagnosis and treatment.

The article describes the current views on the pathogenesis of nonalcoholic fatty liver disease and a short overview of possible methods of therapy. The main mechanisms of antioxidant action of ademetionine in the treatment of NAFLD and the analysis of the evidence base of its effectiveness are discussed. We present clinical cases of a positive impact of ademetionine in NAFLD patients.

Level of serum secretory immunoglobulin A was investigated in alcoholic liver disease (ALD, 59 men and 23 women) and non-alcoholic fatty liver disease (NAFLD, 17 men and 93 women).The data were compared with those of persons without liver pathology (control group, 43 men and 73 women). Moreover, we studied possible associations between ssIgA level and Gln223Arg polymorphism of the LEPR gene. Immunological and DNA diagnostics was performed by means of, respectively, ELISA and allele-specific polymerase chain reaction. We have found that the average level of ssIgA was three times higher in ALD group (11.45±0.82 mg/l), than in the NAFLD group (4.35±0.35 mg/l) or in controls (3,60±0,29 mg/l). SsIgА concentration did not depend on adiposity and gender. The ssIgА concentration proved to be increased in Gln223Arg heterozygotes with NAFLD, when compared with controls. However, the frequency of 223Arg and 223Gln alleles was virtually equal in all observed groups with above-normal concentration of ssIgА, as compared to a sub-group with normal ssIgА concentration. Hence, we have not revealed any significant association between Gln223Arg polymorphism of LEPR and ssIgA level. The data obtained will be useful for studying genetic risk factors in development of infectious mucosаl lesions.

Aim. To determine the value of concomitant non-alcoholic fatty liver disease in patients with arterial hypertension in the progression of rigidity of the main arteries and in increase of risk of cardiovascular complications. Material and methods. A cross-sectional comparative study was conducted. Group 1 (n=50, 35(70%) women, average age 57,4±6,9 years) included patients with arterial hypertension and non-alcoholic fatty liver disease, group 2 (n=50, 40(80%) women, average age 56,5±7,0 years) included patients with arterial hypertension only. The groups were comparable in the main clinical and demographic indicators (p>0,05). A comparative analysis of pulse wave velocity, central aortic pressure, vascular age and a 10-year risk of developing cardiovascular complications in both groups was performed.Results. There is a statistically larger number of patients with metabolic index>7,0 (58,0% vs 28,0%, p=0,0019). It was also established that systolic (121,9±10,9 mm Hg vs 115,9±8,9 mm Hg) and diastolic (82,5±9,3 mm Hg vs 77,4±8,9 mm Hg) aortic pressure, as well as the augmentation index (26,5±8,5% vs 18,6±4,2%), were significantly higher in patients with arterial hypertension and non-alcoholic fatty liver disease than in patients with isolated arterial hypertension. In the 1st group, a statistically significant increased pulse wave velocity was found both in muscular (12,0±3,1 m/s vs 10,6±1,8 m/s) and elastic (10,4±2,8 m/s vs 9,1±1,7 m/s) vessels, which indicates an increase in arterial stiffness. In addition, there was an increase in post-occlusal pulse wave velocity in this category of patients (11,0±3,3 m/s vs 9,4±1,9 m/s, p=0,0037). A significant increase in vascular age in relation to the passport age (60,4 [56,0:68,0] years vs 58,0 [53,0:60,0] years) and an increase in the 10-year fatal risk was detected (2,15 [1,42: 4,63] and 1,05 [0,52: 2,82] %, p = 0,0043 ) were also revealed in patients with arterial hypertension and non-alcoholic fatty liver disease compared to patients with isolated arterial hypertension. Significantly more patients with a high (13 (26,0%) vs 5 (10,0%), p = 0,0332) total cardiovascular risk were observed in group 1 than in group 2.Conclusions. Arterial stiffness was significantly higher in patients with arterial hypertension and non-alcoholic fatty liver disease than in patients with isolated arterial hypertension, which is confirmed by a statistically significant increase in pulse wave velocity and central aortic pressure. Comorbid patients have pronounced endothelial dysfunction, which is confirmed by a significant increase in the post-occlusion rate of the pulse wave. An increase in vascular age in relation to the passport age indicates earlier aging of blood vessels in the 1st group compared with the 2nd group. Patients in the main group have a higher incidence of a high 10-year risk of developing cardiovascular events compared with patients in the control group.

The term steatohepatitis is used for a heterogeneous group of diseases of various etiologies, characterized by a similar morphological picture. Earlier the diagnosis of non-alcoholic fatty liver disease implied the exclusion of other causes of steatohepatitis, in recent years it has been suggested that a combination of various etiological variants of steatohepatitis is possible. The review considers the terminological, epidemiological and pathogenetic aspects of the most common combination: metabolic and alcoholic genesis, the issues of the mutual influence of etiopathogenetic factors and the identification of the predominant process. Issues of existing and prospective pathogenetic and symptomatic therapy are discussed in detail. Treatment of steatohepatitis is based on the elimination of known causal factors and lifestyle modification; therapy includes medications, that have been proven to be effective in certain types of steatohepatitis and symptomatic therapy as well.

Introduction. Today, non-alcoholic fatty liver disease (NAFLD) is increasingly associated with the presence or risk of developing type 2 diabetes (D2). The term “hepatogenic diabetes”, proposed to refer to SD2 in patients with cirrhosis of the liver (CP), has acquired a new meaning, since this combination is of growing interest. The authors analyzed the current literature and summarized data on the pathogenesis, risk factors, and possible therapy of NAFLD.Objective: to evaluate the effectiveness of L-ornithine-L-aspartate (HEPA-Merz, Merz Pharma GmbH & Co) in combination with biguanides in the treatment of NAFLD patients in combination with D2.Materials and methods. The study included 30 patients aged 26 to 60 years with a verified diagnosis of NAFLD of varying degrees of activity in combination with D2. All patients were prescribed combination therapy with the drug HEPA-Merz (“Merz Pharma GmbH and Co”) at a dose of 3 grams 3 times a day in combination with biguanides. The examination was performed on the 1st, 28-th and 56-th days of treatment. In order to determine the effectiveness of therapy, we evaluated the dynamics of clinical symptoms (asthenovegetative, dyspeptic syndromes, pain syndrome in the ball system), biochemical parameters of liver function (changes in markers of cytolysis, cholestasis), lipidogram indicators, glucose levels, glycated hemoglobin, and ultrasound results of abdominal organs.Results. On day 56, asthenovegetative, dyspeptic and pain syndrome were stopped during therapy. Most patients showed a decrease in body weight from 3 to 5 kg. When evaluating changes in biochemical parameters on the 28-th day, the activity of ALT, AST, GGTP and glucose levels significantly decreased against the background of the therapy. On the 56th day of treatment, the activity of transaminases, bilirubin, GGTP and GFR in all patients were within the reference values.Conclusion. Understanding the multifactorial nature of NAFLD and the mechanisms of associated diseases, including D2, will allow us to assess the prognosis of the disease and prescribe adequate timely therapy. The effectiveness of the original ornithineaspartate (Merz Pharma GmbH & Co.) is manifested by a decrease in the processes of cytolysis of hepatocytes, normalization of lipid and carbohydrate metabolism.

Liver involvement in systemic lupus erythematosus is common and in most cases clinical course is asymptomatic, that makes diagnosis difficult. Determination of the cause of the liver involvement is important to select treatment and to evaluate the prognosis of the disease.The aim of the research was to characterize the clinical features of liver involvement in patients with systemic lupus erythematosus and identify the most significant clinical and laboratory parameters for the differential diagnosis of lupus hepatitis.Materials and methods. The study included 313 patients with systemic lupus erythematosus observed in the E.M. Tareev Clinic of Rheumatology, Internal Medicine and Occupational Diseases of I.M. Sechenov First Moscow State Medical University (Sechenov University) in the period from 2001 to 2019. The verification of diagnosis of systemic lupus erythematosus was based on the criteria of the American College of Rheumatology (1997). Patients examination included complete blood count, biochemical and immunological blood tests and an abdominal ultrasonography. In 13 cases hepatic autoantibodies (ASMA, anti-LKM-1, LC-1, SLA-LP, AMA-M2) were analyzed, in 4 – magnetic resonance cholangiopancreatography and in 6 – liver biopsy were made.Results. Liver involvement were represented by an increase of liver enzymes in 58 (18.5%) cases. Chronic viral hepatitis C was diagnosed in 4 (1.3%) patients. Drug-induced hepatitis was found in 17 (5.4%) patients. Autoimmune liver diseases occured in 2 (0.6%) patients. In 2 (0.6%) patients, liver damage was associated with thrombotic microangiopathy (atypical hemolytic uremic syndrome, hereditary thrombophilia). In 15 (4.8%) cases, the most likely diagnosis was NAFLD. Lupus hepatitis was the most likely cause in 18 (5.7%) patients. Differential diagnosis in cases of liver involvement in patients with systemic lupus erythematosus requires assessment of risk factors for various liver diseases, age of the patients, level of liver enzymes, lupus activity, ultrasound signs of liver steatosis and secondary antiphospholipid syndrome.Determining the cause of the liver involvement for the patients with the systemic lupus erythematosus allows establishing better treatment tactic and improvement of the prognosis.

Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are serious health problems. Features of liver steatosis (LS) due to NAFLD and ALD in rural areas, including lipid metabolism indicators, depending on body mass index (BMI), have not been thoroughly studied.Aim. To study the features of lipid metabolism in residents of rural area in LS due to NAFLD and ALD depending on the BMI.Materials and Methods: 1152 residents of a rural therapeutic site were surveyed. Lipidograms and BMI were analyzed in patients with LS at NAFLD and ALD.Results. There were no patients with a reduced BMI in the rural medical site. Persons with BMI ≥ 25 among patients with LS on the background of NAFLD (98.2 %) are significantly more frequent than on the background of ALD (55.1 %) (p < 0.001). Among subjects with normal BMI there were more patients with ALD (44.9 %) than with NAFLD (1.8 %) (p < 0.001). There were no significant differences in age in patients with in NAFLD depending on BMI (p > 0.05). Patients with LS of ALD with an increased BMI were older than those with a normal index (p < 0.05). Also, there were no differences in lipidograms with LS on the background of NAFLD and ALD depending on BMI (p > 0.05). Triglyceride levels (TG) and atherogenic coefficient (AC) were significantly higher (p < 0.05 in both cases) in LS with ALD than in patients with NAFLD. Findings. Disorders of lipid metabolism were found in patients with LS with both increased BMI and normal. At the rural therapeutic site, patients with LS due to ALD have more pronounced lipid metabolism disorders than those ones with NAFLD, regardless of BMI.

Aim. The aim of this review is to analyze and systematize data on the effect of Helicobacter pylori infection on hepatobiliary diseases.Background. Over the past two decades, a growing number of studies have been devoted to the possible involvement of H. pylori infection in the extragastric pathology. The presence of the bacterium was detected in many organs and tissues. Its relationship with the development of idiopathic iron-deficiency anemia, B12 deficiency anemia, idiopathic thrombocytopenic purpura is proved. The possible role of the bacterium in the development of hepatobiliary pathology is also discussed. The presence of the bacterium has been revealed in samples taken from the liver tissue, biliary tract, bile and gallstones of patients suffering from hepatobiliary diseases. The involvement of H. pylori in the formation of gallstones is considered possible. Non-alcoholic fatty liver disease (NAFLD) is more often diagnosed in H. pylori infected individuals compared to those not infected. The progression of inflammation in the liver of any nature is noted in the presence of H. pylori infection. Different species of the Helicobacter genus, including H. pylori, are shown to contribute to the development of liver cancer. However, some researchers report data against the involvement of H. pylori in the pathogenesis of various hepatobiliary diseases.Conclusion. The results obtained by the authors cannot be considered unambiguous, thus requiring further research. Given the high prevalence of H. pylori infection and the significant incidence of hepatobiliary pathology, the confirmation of their relationship can be of great epidemiological, preventive and clinical importance.

Aim. to determine the frequency of intrahepatic cholestasis and its impact on the clinical features of the different forms of non-alcoholic fatty liver disease (NAFLD). Materials and methods. The study involved 163 patients with NAFLD: 92 (56.4%) with hepatic steatosis (HS), 56 (34.4%) with steatohepatitis (SH) and 15 (9.2%) with liver cirrhosis (LC). Diagnosis is based on clinical, laboratory, ultrasound and histological data. Insulin, tumor necrosis factor α (TNF-α), fragments of cytokeratin-18 (FCK-18) were determined by ELISA. The index of insulin resistance (HOMA-IR) was calculated. NAFLD fibrosis score (NAFLD-FS) was determined, taking into account the patient's age, body mass index, presence or absence of carbohydrate metabolism disturbances, levels of ASAT, ALAT, albumin and blood platelets. Results. Cholestatic syndrome was detected in 49 (30.1%) NAFLD patients: in 23 (25%) with HS, in 19 (33.9%) with SH and in 7 (46.7%) with LC. Patients with HS, SH and LC with signs of cholestasis as compared to patients with the same forms of NAFLD without cholestasis had significantly higher levels of the following indicators: aminotransferases, triglycerides, HOMA-IR, TNF-α, FCK-18, NAFLD-FS, - the number of platelets is reduced, indirectly confirming the more rapid development of fibrosis in cholestasis. These findings were consistent with published data on the violation in cholestasis regulatory functions of bile acids, which are ligands of hepatocyte nuclear receptor, responsible for normal homeostasis. Сonclusion. In all forms of NAFLD with cholestasis were detected more pronounced liver cell inflammation, hepatocyte necrosis and apoptosis, fibrosis, disturbance of carbohydrate and lipid metabolism, which contributed to a progressive course of NAFLD and confirmed the need for medical correction of cholestasis, starting with the earliest form of NAFLD - hepatosteatosis.

The aim of this study was to assess the role of obstructive sleep apnea (OSA) in the development of metabolic syndrome. 360 OSA patients were studied. Interactions with glucose intolerance, effects of treatment with continuous positive airway pressure (CPAP) were revealed.

To investigate the association of the polymorphic variants -204AC (rs 3808607) in the CYP7A1 gene with the development of dyslipidemias in healthy individuals, in patients with non-alcoholic fatty liver disease (NAFLD) and in those with NAFLD concurrent with hypothyroidism.DNA samples and lipidograms were examined in 180 patients, including 60 healthy individuals (Group 1), 60 patients with hypothyroidism concurrent with NAFLD (Group 2), and 60 patients with NAFLD (Group 3). All the patients underwent ultrasound examination of the thyroid gland and abdominal cavity organs; FibroMax scores were calculated.All the study groups most frequently showed a homozygous AA genotype (86.6% of cases in Group 1, 80% in Group 2, and 83.3% in Group 3). The development of NAFLD in CC genotype carriers is characterized by the most pronounced changes in lipid metabolism (atherogenic index (AI), 7.32 in Group 3) compared to the genotypes AA (AI, 4.56 in Group 2 and 1.73 in Group 1) and CC (AI, 6.43 in Group 2 and 2.52 in Group 1) in functional insufficiency of thyroid hormones and relative normal conditions.The analysis of the relationship of polymorphic variants CYP7A1 rs 38088607 to lipid metabolic disturbances in the study groups showed that the significantly higher levels of atherogenic cholesterol fractions were determined in the CC genotype compared to AA genotype carriers and they did not depend on the presence of NAFLD and hypothyroidism. The findings make it possible to consider the AA homozygous genotype of variant mutation CYP7A1 rs 38088607 as protective against dyslipidemia. However, in functional insufficiency of thyroid hormones, the level of triglycerides is significantly higher in both genotypes, which suggests that hypothyroidism plays an essential role in the development of dyslipidemia and NAFLD.Цель исследования. Изучение связи полиморфных вариантов -204АС (rs 3808607) гена CYP7A1 с развитием дислипидемий у практически здоровых лиц, у больных с неалкогольной жировой болезнью печени (НАЖБП) и при сочетании НАЖБП с гипотиреозом. Материалы и методы. Исследовали образцы ДНК и липидограммы 180 пациентов (1-я группа - 60 здоровых, 2-я группа - 60 больных с гипотиреозом и НАЖБП, 3-я группа - 60 больных с НАЖБП). Все пациенты прошли ультразвуковое исследование щитовидной железы, органов брюшной полости; рассчитан тест ФиброМакс. Результаты. Во всех обследуемых группах чаще всего встречался гомозиготный генотип АА (86,6% случаев в 1-й группе, 80% случаев во 2-й группе и 83,3% случаев в 3-й группе). Развитие НАЖБП у носителей генотипа СС характеризуется наиболее выраженными изменениями липидного метаболизма (индекс атерогенности - ИА 7,32 в 3-й группе) по сравнению с генотипами АА (ИА 4,56 во 2-й группе и 1,73 в 1-й группе) и СС (ИА 6,43 во 2-й группе и 2,52 в 1-й группе) при состояниях функциональной недостаточности тиреоидных гормонов и относительной нормы. Заключение. Проведенный анализ связи полиморфных вариантов rs 38088607 гена CYP7A1 с нарушением липидного обмена в обследуемых группах показал, что достоверно более высокие уровни атерогенных фракций холестерина определялись при генотипе СС по сравнению с носителями генотипа AA и не зависили от наличия НАЖБП и гипотиреоза. Полученные данные позволяют рассматривать гомозиготный генотип АА как протекторный по отношению к дислипидемии вариант мутации rs 38088607 гена CYP7A1. Однако при состояниях функциональной недостаточности тиреоидных гормонов уровень триглицеридов достоверно выше при обоих генотипах, что свидетельствует о существенной роли гипотиреоза в развитии дислипидемий и НАЖБП.

To evaluate clinical features and metabolic disorders in men and women with non-alcoholic fatty liver disease (NAFLD).Цель исследования. Оценка особенностей клинического течения и метаболических нарушений у мужчин и женщин с неалкогольной жировой болезнью печени (НАЖБП). Материалы и методы. Обследовали 153 больных НАЖБП, из них 97 мужчин и 56 женщин. В сравнительном плане изучали клинические проявления НАЖБП. У всех пациентов НАЖБП верифицирована впервые. Исследовали функциональное состояние печени, показатели липидного, углеводного и порфиринового обмена, инсулинорезистентность (ИР). Результаты. Расстройства в функциональных показателях печени и цитолиза чаще обнаруживались у женщин. При этом достоверных различий по степени их выраженности не наблюдалось. Дисметаболизм порфиринов, расстройства в липидном обмене, гиперинсулинизм, ИР доминировали у мужчин. Более высокая гипертриглицеридемия в сочетании с ИР позволяет предположить, что сочетание этих нарушений и их бо`льшая выраженность могут способствовать формированию стеатоза печени у мужчин значительно раньше. Заключение. Основные патофизиологические и патогенетические процессы формирования НАЖБП (ИР и дислипидемия) доминируют у мужчин. Это дает основание считать мужской пол достоверным фактором риска формирования НАЖБП.

In a review based on an analysis of numerous studies the expediency of incorporating drugs essential phospholipids (eg, dietary supplements Hepaguard Active ®) at a range of therapeutic and preventive measures in general therapeutic practice in patients with obesity, in the presence of conditions / diseases and complications associated with it, and especially metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD). Recently described prebiotic effect of Hepaguard active ®allows you to expand the scope of its application and use in patients with impaired intestinal microbiocenosis.

To study the results of dynamic liver ultrasound elastography (LUE) in assessing the risk of complications of liver cirrhosis (LC) of different etiologies and to elaborate a monitoring program for estimation of the predictive value of elastography in patients with LC.A total of 194 patients with LC of different etiologies, including 56 patients with alcoholic cirrhosis, 48 with LC and an outcome of nonalcoholic fatty liver disease, 53 with LC and an outcome of chronic hepatitis C, 23 with LC and an outcome of chronic hepatitis B, and 14 with an outcome of coinfection with hepatitis B and D viruses, were examined. An analysis was made between the presence of a number of LC complications and the results of LUE, by constructing the receiver operating characteristic (ROC) curves to select LUE threshold values, in which there was a high risk for LC complications (esophageal varices, bleeding esophageal varices, hepatic encephalopathy, and ascites).The investigation could obtain liver elastography threshold values expressed in kilopascals (kPa), which were proposed for use as a prognostic sign of the presence of complications caused by LC and assessed liver elastography threshold values for its mortality prediction. The predictive value of positive LUE results in determining the risk of different complications was 75.7 to 92.5%; that of negative results was 70 to 92.9%. An algorithm for individualized diagnostic and treatment policy was elaborated in relation to the liver elastography results obtained during the primary examination of a patient.The dynamic LUE findings in patients with LC of different etiologies suggest that the proposed LUE threshold values are efficient and may be used in practical healthcare, which will be able to timely correct management tactics for a patient and to monitor his treatment.Цель исследования. Изучить результаты динамической ультразвуковой эластографии печени (УЗЭП) в оценки вероятности наличия у больных осложнений цирроза печени (ЦП) различной этиологии и разработать программу мониторинга для оценки прогностического значения УЗЭП у больных ЦП. Материалы и методы. Обследовали 194 пациента с ЦП различной этиологии: 56 больных ЦП алкогольной этиологии, 48 больных ЦП в исходе неалкогольной жировой болезни печени, 53 больных ЦП в исходе хронического вирусного гепатита С, 23 больных ЦП в исходе хронического гепатита B и 14 в исходе хронического вирусного гепатита В+D. Проведен анализ между наличием ряда осложнений ЦП и результатами УЗЭП с построением характеристических (ROC) кривых для выбора пороговых значений УЗЭП, при которых высока вероятность наличия осложнений ЦП (варикозно-расширенные вены пищевода — ВРВП, кровотечение из ВРВП , печеночная энцефалопатия, асцит). Результаты. В ходе работы получены пороговые значения УЗЭП, предполагаемые для использования в качестве прогностического признака наличия осложнения ЦП, проведена оценка пороговых значений УЗЭП для прогноза смертности от ЦП. Прогностическая ценность положительных результатов УЗЭП для определения вероятности наличия различных осложнений составила от 75,7 до 92,5%, прогностическая ценность отрицательных результатов — от 70 до 92,9%. Разработан алгоритм индивидуализированной диагностической и лечебной тактики в зависимости от получаемых в ходе первичного обследования пациента результатов УЗЭП. Заключение. Полученные результаты динамической УЗЭП у больных ЦП различной этиологии свидетельствуют о работоспособности предложенных пороговых значений УЗЭП и свидетельствуют о возможности их использования в практическом здравоохранении, что позволит своевременно корректировать тактику ведения пациента и проводить мониторинг лечения.

Scientifically proven close relationship of nonalcoholic fatty liver disease with development of metabolic syndrome and its individual components involves the conclusion that the target organ in metabolic symptom, even regardless of the severity of obesity, the liver occupies a dominant position, as the body undergoes the first characteristic of non-alcoholic fatty liver disease changes, involving violation of metabolism in the body. Dislipoproteinemia plays an important role in the formation of metabolic syndrome in obesity and other obesity-associated diseases. Altered liver function are the root cause of violations of processes of lipid metabolism and, consequently, abnormal functioning of the liver may be a separate, additional and independent risk factor for development of dyslipidemia and obesity as the main component of the metabolic syndrome.

Today, the role and importance of the first contact medical specialist (physician or general practitioner) is increasing in the diagnosis and management of patients with obesity and nonalcoholic fatty liver disease today. The article discusses the diagnostic algorithm for obesity based on the AACE/ACE-2014 classification, and the potential of essential phospholipids in the therapeutic and prophylactic recommendations for patients with NAFLD associated with obesity.

Non-alcoholic fatty liver disease is one of the most common pathologies of the liver in developed countries. On the average, its prevalence reaches 20 %. In some patients, non-alcoholic fatty liver disease occurs with inflammation, vacuolization of hepatocytes and subsequent development of fibrosis and cirrhosis. This type of non-alcoholic fatty liver disease is called non-alcoholic steatohepatitis. Patients with non-alcoholic steatohepatitis are at higher risk of complications, for example, hepatocellular carcinoma or varicose veins of the esophagus. Specific therapy for non-alcoholic steatohepatitis has not been yet developed. The main recommendations for patients are lifestyle changes that have some effectiveness in reducing steatosis and inflammation activity. However, rapid progressive course of non-alcoholic steatohepatitis is not always possible to be controlled only by low calorie diet and increased physical activity. For the treatment of patients with non-alcoholic steatohepatitis, we can also use a non-specific therapy that can slow disease progression and reduce inflammation. Since the main mechanism of pathogenesis in non-alcoholic steatohepatitis is oxidative stress, researchers are actively investigating the effect of different antioxidants and their combinations. Today there is a large number of studies of these drugs. There are significant limitations of a large part of these studies: the lack of thorough monitoring of compliance and duration of lifestyle modification. Indeed, in this situation particular interest must be provided for those patients with a high activity of non-alcoholic steatohepatitis that persists despite strict adherence to the recommendations in lifestyle changes. Additional research required to assess the effectiveness of pharmacological therapy in patients with non-alcoholic steatohepatitis with long-term lifestyle changes. In this article, we will present a description and results of single-centre controlled trial to assess the effectiveness of Prohepar in patients with non-alcoholic steatohepatitis with persistent inflammatory activity on the background of adequate modification of lifestyle., Неалкогольная жировая болезнь печени (НАЖБП) является одним из самых распространенных заболеваний печени в развитых странах. В среднем ее частота достигает 20 %. У части пациентов ­НАЖБП протекает с наличием воспаления, вакуолизации гепатоцитов и последующим развитием фиброза и цирроза. Такой вариант течения НАЖБП называют неалкогольным стеатогепатитом (НАСГ). Пациенты с НАСГ подвержены более высокому риску развития осложнений, например возникновению гепатоцеллюлярной карциномы или варикозного расширения вен пищевода. Специфическая терапия НАСГ на сегодняшний день еще не разработана. Основные рекомендации для пациентов заключаются в изменении стиля жизни, что имеет определенную эффективность в снижении уровня стеатоза и активности воспаления. Однако быстро прогрессирующее течение НАСГ не всегда возможно контролировать одним только снижением калорийности диеты и увеличением уровня физической активности. Для лечения пациентов с НАСГ также используется неспецифическая терапия, которая способна замедлять прогрессирование заболевания и снижать уровень воспаления. Так как основным механизмом патогенеза НАСГ является оксидативный стресс, исследователи активно изучают действие различных антиоксидантов и их комбинаций. На сегодняшний день представлено большое количество результатов исследований подобных препаратов. Существенным ограничением большой части данных исследований является отсутствие тщательного мониторинга комплайенса и длительности выполнения пациентами рекомендаций по изменению образа жизни. Ведь в данной ситуации особый интерес должны представлять именно те пациенты, у которых высокая степень активности НАСГ сохраняется, несмотря на строгую приверженность к рекомендациям по изменению стиля жизни. В связи с этим требуется проведение дополнительных исследований по оценке эффективности фармакологической терапии у пациентов с НАСГ на фоне длительного изменения образа жизни. В этой статье мы приведем описание и результаты одноцентрового контролируемого исследования по оценке эффективности препарата Прогепар у пациентов с НАСГ с персистенцией активности воспалительного процесса на фоне модификации образа жизни., Неалкогольна жирова хвороба печінки (НАЖХП) є одним із найпоширеніших захворювань печінки в розвинених країнах. У середньому частота даної патології досягає 20 %. У частини пацієнтів перебіг НАЖХП асоціюється з наявністю запалення, вакуолізації гепатоцитів і подальшим розвитком фіброзу та цирозу. Такий варіант перебігу НАЖХП називають неалкогольним стеатогепатитом (НАСГ). Пацієнти з НАСГ мають більш високий ризик ускладнень, наприклад розвитку гепатоцелюлярної карциноми або варикозного розширення вен стравоходу. На сьогодні не існує специфічної терапії НАСГ. Основні рекомендації полягають у модифікації стилю життя, що має певну ефективність у зниженні рівня стеатозу та активності запалення. Однак швидкий прогресуючий перебіг НАСГ не завжди можливо контролювати одним тільки зниженням калорійності дієти та збільшенням рівня фізичної активності. Для лікування пацієнтів із НАСГ також використовується неспецифічна терапія, що здатна сповільнювати прогресування захворювання і знижувати рівень його активності. З огляду на те, що основним механізмом патогенезу НАСГ є оксидативний стрес, дослідники активно вивчають дію різних антиоксидантів та їх комбінацій. На сьогодні представлена значна кількість досліджень подібних препаратів. Істотним обмеженням значної частини даних досліджень є відсутність ретельного моніторингу комплайєнсу та тривалості дотримання пацієнтами рекомендацій щодо зміни способу життя. Адже в даній ситуації особливий інтерес повин-ні становити саме ті пацієнти, у яких зберігається високий ступінь активності НАСГ, незважаючи на суворе дотримання немедикаментозних рекомендацій. У зв’язку з цим необхідне проведення додаткових досліджень з оцінки ефективності фармакологічної терапії в пацієнтів із НАСГ на тлі тривалої зміни способу життя. У цій статті ми наведемо опис і результати одноцентрового контрольованого дослідження з оцінки ефективності препарату Прогепар у пацієнтів із НАСГ із персистенцією активності запального процесу на фоні модифікації способу життя.

В статье освещается одна из наиболее часто встречаемых патологий печени неалкогольная жировая болезнь печени (НАЖБП), обсуждаются современные концепции этиологии, патогенеза, принципы диагностики и новейшие походы к консервативному и хирургическому лечению данного заболевания. Описывается патофизиология инсулинорезистентности, метаболического синдрома и ряда других клиническиассоциированных с НАЖБП состояний. Подробно рассматриваются патогенетические аспекты развития фиброза при НАЖБП и описываются современные возможности и ограничения методов визуализации в диагностике степени стеатоза и стадии фиброза печени, ультразвукового исследования и сывороточных маркеров. Обоснованы подходы к обследованию и ведению пациентов с НАЖБП на разных этапах развития заболевания., The article discusses one of the most frequent hepatic pathologies, nonalcoholic fatty liver disease, and current concepts of its etiology, pathogenesis, diagnostic principles, and the latest approaches to conservative and surgical treatment. Pathophysiology of insulin resistance, metabolic syndrome, and other conditions clinically associated with nonalcoholic fatty liver disease are described. The authors deepened the insight into mechanisms of fibrosis development, uptodate possibilities and limitations of imaging methods in diagnosis of the degree of steatosis and the stage of liver fibrosis, ultrasound, and serum markers. Clinical substantiation of the need to create an algorithm for examining and managing patients with nonalcoholic fatty liver disease at different stages of this condition and early verification of steatosis has an undoubted merit., №2 (2019)

There are demonstrated the results of the investigation of the course oral use of aqueous solution «Poltava bishofit» in patients with non-alcoholic fatty liver disease. The effectiveness of the proposed non-drug treatment of those patients manifested in improvement of the disease clinical course, restoration of blood lipid spectrum, insulin resistance reduction, amelioration of comorbid gastrointestinal pathology, that rationalize the use of aqueous solution «Poltava bishofit» for the treatment of non-alcoholic fatty liver disease., Изложены результаты исследования внутреннего курсового приема водного раствора «Полтавский бишофит» у больных с неалкогольной жировой болезнью печени (НАЖБП). Продемонстрирована эффективность предложенного немедикаментозного лечения данной категории больных в улучшении клинического течения заболевания, восстановлении липидного спектра крови, уменьшении инсулинорезистентности, улучшении течения сопутствующей патологии органов желудочно-кишечного тракта, что патогенетически обосновывает использование водного раствора «Полтавский бишофит» в лечении больных с НАЖБП., Викладено результати дослідження внутрішнього курсового прийому водного розчину «Полтавський бішофіт» у хворих на неалкогольну жирову хворобу печінки (НАЖХП). Продемонстрована ефективність запропонованого немедикаментозного лікування даної категорії хворих щодо поліпшення клінічного перебігу захворювання, відновлення ліпідного спектра крові, зменшення інсулінорезистентності, поліпшення перебігу супутньої патології органів шлунково-кишкового тракту, що патогенетично обґрунтовує використання водного розчину «Полтавський бішофіт» у лікуванні хворих на НАЖХП.

Diabetes mellitus (DM) type 2 in clinical practice is often associated with non-alcoholic fatty liver disease (NAFLD), which has a number of clinical and morphological forms and develops in patients who do not abuse alcohol. The combination of DM type 2 and NAFLD is associated not only with a high risk of developing liver cirrhosis and hepatocellular carcinoma in these patients. Although all aspects of the etiology of NAFLD is not fully known, it is points to the role of insulin resistance in its development. This concept has facilitated a number of clinical studies using metformin as the insulin sensitizer in insulin-resistant patients with NAFLD. The findings emphasize the importance of metformin in the treatment of NAFLD in combination with a hypocaloric diet and the control of body weight. It is also reported about other tissue effects of metformin in NAFLD., Сахарный диабет (СД) 2-го типа в клинической практике часто сочетается с неалкогольной жировой болезнью печени (НАЖБП), которая имеет несколько клинико-морфологических форм и развивается у пациентов, не злоупотребляющих алкоголем. Сочетание СД 2-го типа и НАЖБП связано не только с высоким риском развития цирроза печени и гепатоцеллюлярной карциномы у данной категории больных. Хотя все аспекты этиологии НАЖБП до конца не известны, указывается на роль инсулинорезистентности в ее развитии. Эта концепция содействовала проведению нескольких клинических исследований с применением метформина как инсулинового сенситайзера у инсулинорезистентных пациентов с НАЖБП. Полученные результаты подчеркивают значение метформина в лечении НАЖБП в сочетании с гипокалорийной диетой и контролем массы тела. Сообщается также о других тканевых эффектах метформина при НАЖБП., Цукровий діабет (ЦД) 2-го типу в клінічній практиці часто поєднується з неалкогольною жировою хворобою печінки (НАЖХП), що має кілька клініко-морфологічних форм і розвивається в пацієнтів, які не зловживають алкоголем. Поєднання ЦД 2-го типу і НАЖХП пов’язане не тільки з високим ризиком розвитку цирозу печінки й гепатоцелюлярної карциноми в даної категорії хворих. Незважаючи на те, що всі аспекти етіології НАЖХП до кінця не відомі, вказують на роль інсулінорезистентності в її розвитку. Ця концепція сприяла проведенню кількох клінічних досліджень із вживанням метформіну як інсулінового сенситайзеру в інсулінорезистентних пацієнтів із НАЖХП. Отримані результати підкреслюють значення метформіну в лікуванні НАЖХП у поєднанні з гіпокалорійною дієтою й контролем маси тіла. Повідомляється також про інші тканеві ефекти метформіну при НАЖХП.

Endothelial dysfunction as a threat of the hepatic steatosis development in children N.N. Varlamova, I.V. Solodkova, E.V. Sinelnikova, V.G. Chasnyk St. Petersburg State Pediatric Medical University, Saint Petersburg, Russian Federation This article discusses the mechanisms of formation of endothelial dysfunction in non-alcoholic fatty liver disease (NAFLD) in children. Endothelial dysfunction is associated with the development of insulin resistance (IR), which plays a leading role in the pathogenesis of NAFLD. The article describes the relationship of endothelial dysfunction (ED) with birth weight and clinical consequences in the future. Aim: to study endothelial function in children with NAFLD and assess the risk of developing severe forms of hepatic steatosis. Patients and Methods: 140 adolescents with NAFLD were examined in the Department of Endocrinology of the St. Petersburg State Pediatric Medical University Clinic. Patients were divided into 3 groups depending on birth weight: group I — 42 patients with low weight, group II — 50 patients with overweight, and group III — 48 people with normal birth weight. All patients underwent an ultrasound of liver. The study of ED was performed by a non-invasive method for testing the brachial artery (BA) reactivity using the GE Logiq S8 ultrasound scanner by measuring the endothelium-dependent flow-mediated vasodilation in the BA. Biochemical parameters of blood were also taken into account. Results: the initial diameters of BA in two groups did not have significant deviations from normal values. In patients of group I at the age of 8–11 years, a more pronounced violation of vasodilation was detected in comparison with the parameters of children of the same age in groups II (4.5±3.1 vs. 10.5±2.5, p Conclusion: prognosis of the NAFLD development for the assessment of ED, and hence, an implementation of preventive measures is possible with the use of ultrasound diagnostics in risk group children for this nosology. Key words: non-alcoholic fatty liver disease, hepatic steatosis, endothelial dysfunction, intrauterine growth retardation. For citation: Varlamova N.N., Solodkova I.V., Sinelnikova E.V., Chasnyk V.G. Endothelial dysfunction as a threat of the hepatic steatosis development in children. Russian Journal of Woman and Child Health. 2018;1(2):137–140.

Aim. To identify trends in the structure of patients with liver diseases, in particular hepatocellular cancer (HCC), by analysing the experience of two specialised medical centres.Materials and methods. A retrospective analysis of the medical records of hepatological patients who sought medical treatment at to the V.Kh. Vasilenko Clinic of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology of the Sechenov University in 2013, 2014 and 2017 (total 2459 patients) was carried out. The number of patients with chronic viral hepatitis (CVH) was 651, with non-alcoholic fatty liver disease (NAFLD) — 590, with alcoholic liver disease (ALD) — 66, with autoimmune liver diseases — 416, with liver cirrhosis (LC) of any etiology 407, other liver diseases — 329. A retrospective analysis of the medical records of patients with HCC who were examined and treated at the N.V. Sklifosovsky Research Institute for Emergency Medicine in the period from 2008 to 2017 (n = 86) was carried out.Results. The ratio of patients with chronic hepatitis C and B in 2013–2017 significantly changed. An almost twofold decrease in the number of patients with chronic hepatitis C (210 patients in 2013 and 141 patients in 2017) and an increase in the number of patients with chronic hepatitis B (20 patients in 2013 and 45 patients in 2017) was observed. An almost twofold increase in the total number of NAFLD patients was detected (163 patients in 2013 and 276 patients in 2017). The number of ALD patients increased from 12 patients in 2013 to 31 patients in 2017. The proportion of patients with autoimmune liver diseases in the overall structure of patients who applied to the department was 20 % in 2013, 13.6 % in 2014 and 10.8 % in 2017. An almost twofold decrease in the number of patients with alcoholic LC and LC associated with HBV was observed (73 patients and 17 patients in 2013 and 38 patients and 6 patients in 2017, respectively) as well as a noticeable increase in the number of patients with alcoholic LC and LC associated with HCV (6 patients and 51 patients in 2013 and 26 patients and 75 patients in 2017, respectively). In the analysis of HCC patients, the ratio of men to women was 3:1 (64 men and 22 women), the median age was 54.5 years (IQR 48–59). The median time from the establishment of chronic liver disease to the detection of HCC was 7.5 years (IQR 3–14.5). In 86 % of cases, the HCC development was preceded by cirrhosis (Child-Pugh A: n = 24; Child-Pugh B: n = 30; Child-Pugh C: n = 20), in 14 % — by chronic hepatitis. Viral liver lesions were the leading cause of HCC in 79 % (n = 68), ALD in 4 % (n = 3), NAFLD in 1 % (n = 1), AIH in 1 % (n = 1). In 10 % (n = 9), a combined liver lesion was observed, in 5 % (n = 4), no previous liver disease was known. The highest five-year survival rate (100 %) was found in the group of patients who received antiviral therapy (AVT) before and after liver transplantation.Conclusions. NAFLD, ALD, and chronic hepatitis B patients began to seek medical help more frequently. An increase in the number of patients with autoimmune LC and LC associated with chronic hepatitis C virus (HCV) infection was observed. The conducted analysis of trends in the structure of HCC patients showed that chronic HCV and HBV infection is the main prerequisite for the development of cancer. Liver transplantation is the most effective treatment for HCC. AVT before and after liver transplantation allows a statistically significant increase in the five-year posttransplant survival of HCC patients with chronic hepatitis C to be achieved.

Non-alcoholic fatty liver disease (NAFLD) is a group of conditions closely associated with obesity that are among the most common and socially significant liver diseases in the modern Western world. The emergence and progression of NAFLD from simple steatosis to non-alcoholic steatohepatitis with the subsequent development of fibrosis are the leading factors in the pathogenesis of a significant proportion of the most severe liver pathologies, such as cirrhosis and hepatocellular carcinoma, as well as extrahepatic metabolic complications of NAFLD, such as insulin resistance and type 2 diabetes mellitus. The inflammatory component is one of the most important factors in the pathogenesis of NAFLD, particularly in the context of the progression of simple steatosis to non-alcoholic steatohepatitis. At the same time, the role of the most important mediators of the inflammatory response, innate immunity receptors and the Toll-like receptors in particular, in the pathogenesis of NAFLD has been poorly studied. In the present work, we first used the bioinformatics analysis of the publicly available gene expression databases to demonstrate that only TLR1, TLR2, TLR3 and TLR4 were significantly expressed in the healthy human liver. We then used the reverse transcription PCR to measure the mRNA expression levels of TLR2, TLR3, and TLR4, as well as those of the important pro-inflammatory mediators tumor necrosis factor (TNF) and interleukin-6 (IL-6), in the liver biopsy specimens obtained from 20 patients with NAFLD (simple steatosis, n = 10; non-alcoholic steatohepatitis, n = 10), as well as from 4 obese patients with clinical suspicion for NAFLD but no histological signs of NAFLD in their liver biopsies. We found a significant increase in the expression of TLR2, TLR3 and TLR4 mRNA in liver biopsy samples obtained from patients with non-alcoholic steatohepatitis as compared to those obtained from controls without histological signs of NAFLD. We were also able to demonstrate the association between the hepatic levels of TLR2, TLR3 and TLR4 mRNAs with the histological degree of liver damage as evidenced by the degree of steatosis and balloon dystrophy of hepatocytes, as well as with the plasma levels of uric acid, the important endogenous stimulator of innate immunity. Our data indicate the possible involvement of innate immunity, particularly the Toll-like receptors, in the pathogenesis of NAFLD.

Aim. To analyse the dynamics of morbidity and mortality from diseases of the digestive system, as well as the quality of medical care for gastroenterological patients in the Krasnodar Krai.Materials and methods. The analysis was carried out according to C 51 “Distribution of deaths by gender, age groups and causes of death” form of the Territorial Authority of the Federal State Statistics Service for the Krasnodar Krai for the period from 2006 to 2018, as well as on the basis of the “Demography” block database of the Parus software of the healthcare management system of the Krasnodar Krai for 6 months of 2019. 1341 medical records of patients receiving outpatient medical care and the medical records of people who had died from digestive diseases in 2017-2019 were reviewed.Results. Digestive diseases (DD) occupy the fourth place (7.1 %) in the structure of the general morbidity of the population in the Krasnodar Krai. Over the study period (13 years), the structure of mortality from DD has not changed significantly among the region’s population. About 70% of the causes of death from DD among people of working age account for liver diseases. The pathology of the pancreas takes the second place (13.5 %). The peptic ulcer of the stomach, duodenum and “other diseases of the digestive system” (8.8 % and 7.7 %, respectively) are represented in almost equal shares. In the etiological structure of liver cirrhosis, viral (39 %) and alcoholic (36 %) liver diseases are leading. The frequency of viral liver lesions tends to decrease, while the proportion of liver cirrhosis in the outcome of non-alcoholic fatty liver disease (NAFLD) progressively increase, having reached 7 % in 2017–2018. In the group of patients with inflammatory diseases of the pancreas, men prevail (66.9 %), often those abusing alcohol. The third leading cause of mortality from DD in the Krasnodar Territory is pathological conditions that occurred in the upper gastrointestinal tract (acute stomach ulcer, duodenal ulcer with bleeding, perforation) in older age groups taking antiplatelet agents and non-steroidal anti-inflammatory drugs (71.8 %). Conclusions. The main causes of death among the population of the Krasnodar Krai from diseases of the digestive system at a young age are alcohol consumption with unhealthy consequences. At the same time, people of older age groups die from a lack of prevention of ulceration and inadequate eradication of Helicobacter pylori in patients taking non-steroidal anti-inflammatory drugs and antiplatelet agents.

Recently, the internist-practitioner does not routinely assess glomerular filtration rate (GFR) in there no risk factors for chronic kidney disease (CKD). However, recent data shows that in non-alcoholic fatty liver disease (NAFLD) it is necessary to assess GFR even without any classic risk factors for CKD. Early awareness of kidney damage in chronic heart failure patients (CHF) and NAFLD might help to select those requiring further investigation and treatment, taking into account comorbidity. Aim. To assess functional condition of kidneys in CHF patients with liver steatosis. Material and methods. Totally, 77 CHF patients included. All patients had confirmed CHF diagnosis by N-terminal Brain pro-natriuretic peptide assay. The severity of clinical condition in CHF was assessed, functional status of patient. All patients underwent clinical and biochemical blood sampling, electrocardiography, ultrasound liver imaging. The heart chambers sizes were assessed, walls thickness by echocardiography. All patients had the GFR by CKD-EPI calculated, as the Fatty Liver Index (FLI), NAFLD Fibrosis Score (NFS). Results. More than a half (66%) of patients with CHF had C2 stage of CKD, 6% — С1, 12% — С3а, 9% — С3б, 4% — С4 stage of CKD. Patients with С5 were absent. Mean GFR was 65,4±14,4 ml/min/1,73 m2. In statistical analysis it was revealed that while there is an increase of SCAHF points, there is parallel increase of CKD stage (p=0,0027). Higher glucose level, higher the stage of CKD (p=0,0022). It was found, that while there is and increase of CKD, right atrium size also increases (p=0,044). With more severe renal damage in CHF, higher the level of PIIINP myocardium fibrosis marker (p=0,047). According to FLI, in 40% of patients there is high chance for liver steatosis, in 34% of patients the data on steatosis was absent, in 26% was intermediate. According to NFS, 26% patients had high probability of liver fibrosis, 9% — did not have, 65% were in a “grey zone”. In analysis of relations there was found that while increasing NFS, GFR does decrease, and CKD stage increases (p=0,049). Conclusion. Patients with NAFLD and CHF do need GFR assessment. Early finding of renal involvement in CHF with NAFLD would help to select patients for further investigation and therapy prescription, taking into account comorbidity.

Recent decades there was a growing amount of people with obesity, hence the amount of the associated pathologies such as arterial hypertension, heart failure, non-alcoholic fatty liver disease. In obesity the most common for all diseases is a chronic “smoldering” inflammation. Inflammatory reaction can be a cause of apoptosis and/or necrosis of the cells (cardiomyocytes, hepatocytes, pancreocytes, endoteliocytes). Terminal pathway of chronic inflammation and tissues damage is usually related to fibrosis — the most common and widespread outcome of many diseases. An important issue is diagnostics of fibrosis at early stages. The main interest for the study is focused on noninvasive assessment of fibrosis at early stages, e. g. the levels of galectin-3. This marker is regarded as possible profibrotic molecule, potential marker of liver and heart fibrosis. Perhaps the investigation on galectin-3 might help in evaluation of the risk of fibrosis development and progression assessment.

The article deals with the results showing the existence of the preconditions for the formation of non-alcoholic fatty liver disease (NAFLD) in patients with metabolic disorders. This is due to reliable association of alleles and genotypes of polymorphic marker of adiponectin gene-1 (ADIPOR1) in patients with NAFLD. It is found that the SNP in the promoter of the gene ADIPOR1 is associated in patients with NAFLD with high content of fat in the liver, development of insulin resistance, and more high levels of glycosylated hemoglobin, and gamma-glutamyl transpeptidase. Knowing the features of genotype of patients with NAFLD is required for selection of individualized treatment algorithm., В статье представлены результаты, свидетельствующие о существовании предпосылок к формированию неалкогольной жировой болезни печени (НАЖБП) у пациентов с метаболическими нарушениями. Это обусловлено достоверной ассоциацией аллелей и генотипов полиморфного маркера гена адипонектина-1 (ADIPOR1) у пациентов с НАЖБП. Установлено, что SNP в промоторе гена ADIPOR1 ассоциирован у больных с НАЖБП с повышенным содержанием жира в печени, развитием инсулинорезистентности и более высокими уровнями гликозилированного гемоглобина и гамма-глутамилтранспептидазы. Знание особенностей генотипа больных с НАЖБП необходимо для выбора индивидуализированного алгоритма лечения., У статті подані результати, що свідчать про існування передумов до формування неалкогольної жирової хвороби печінки (НАЖХП) у пацієнтів із метаболічними порушеннями. Це обумовлено вірогідною асоціацією алелей і генотипів поліморфного маркера гена адипонектину-1 (ADIPOR1) у пацієнтів із НАЖХП. Установлено, що SNP у промоторі гена ADIPOR1 асоційований у хворих на НАЖХП із підвищеним умістом жиру в печінці, розвитком інсулінорезистентності і більш високими рівнями глікозильованого гемоглобіну и гамма-глутамілтранспептидази. Знання особливостей фенотипу та генотипу хворих на НАЖХП необхідне для вибору індивідуального алгоритму лікування.