Abstract Funding Acknowledgements None. Aim To study the spectrum of liver damage in patients with acute decompensated heart failure (ADHF). Materials and methods Included were 566 patients hospitalized with ADHF, NYHA class II–IV, 66% men, mean age 72,4±11,4 years. All patients underwent laboratory and instrumental examination, the degree of steatosis and liver density were determined by transient elastometry methods, with an assessment of the controlled ultrasound attenuation parameter (CAP - Controlled Attenuation Parameter, S, dB/m) using a device according to standard methods. CAP values <294 dB/m with steatosis degree 0 - S0, 295-309 dB/m - S1, 310-330 dB/m - S2, ≥331 dB/m - S3. Liver density was used: ≤5,8 kPa – normal liver density, ≥5,9 – stage F1, ≥7,2 kPa – F2, ≥9,5 kPa – F3, ≥12,5 kPa – F4. Laboratory manifestations of liver damage were considered to be increased aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase. Results The incidence of hepatic steatosis (≥S1) among patients with ADHF was 29%. Among patients with liver steatosis, minimal steatosis (S1) was detected in 19% of cases, moderate steatosis (S2) - 28,6%, severe steatosis S3 - 52,4%. In patients with steatosis, the frequency of laboratory indicators of liver damage was 53%, and in patients without steatosis - 49,2%. Liver density ≥ F1 was observed in 79,5% of patients. Stage F1 was diagnosed in 10,4% of cases, F2 - in 11%, F3 - 12,7%, F4 - 44,5%. However, no relationship was found between the severity of steatosis and liver density (p>0,05). Multivariate Cox regression analysis showed that extremely low CAP values (<234 dB/m) were associated with a worse prognosis and higher risk of HF mortality during the 3-year follow-up period (adjusted hazard ratio (aHR) 1,57 95% confidence interval (CI) 1,08–2,31, p=0,019) after adjustment for established risk factors and potential confounders. The presence of increased liver density >15,9 kPa was also associated with a worse prognosis of the risk of death from HF during the 3-year follow-up period by Cox multivariate analysis (aHR 1,24, 95% CI 1,01–1,52, p= 0,040). Conclusion Thus, extremely low CAP values (<234 dB/m) and the presence of a marked increase in liver density (>15,9 kPa) were associated with a worse prognosis in patients with ADHF during the 3-year follow-up period.

To study N-terminal pro-brain natriuretic peptide (NTproBNP) levels in patients with non-alcoholic fatty liver disease (NAFLD) and acute decompensated heart failure (ADHF) and to evaluate its impact on clinical outcomes.

Aim To study the incidence and effect of non-alcoholic fatty liver disease (NAFLD) on clinical outcomes in patients with decompensated chronic heart failure (DCHF).Material and methods The study included 338 patients with NYHA functional class III-IV DCHF (51.2% men, mean age 72.8±11.7 years), arterial hypertension (AH) in 90%, myocardial infarction in 37%, atrial fibrillation in 64%, chronic kidney disease (CKD) in 42%, type 2 diabetes mellitus (T2DM) in 35%, left ventricular ejection fraction (LVEF) <40% in 27%. NAFLD was diagnosed based on the 2021 Clinical Guidelines of the Russian Scientific Medical Society of Therapists and the Scientific Society of Gastroenterologists of Russia. The stage of liver steatosis was determined using transient elastometry with assessment of the controlled attenuation parameter (CAP) of ultrasound (S, dB/m) using a FibroScan device. Threshold CAP values <294 dB/m corresponded to the degree of steatosis: S0; S1, 295-309 dB/m; S2, 310-330 dB/m; S3, ≥331 dB/m.Results NAFLD was diagnosed in 28.9% of patients. The patients were divided into two groups: group 1 included patients with CHF and NAFLD (n=98 (28.9%), 50.0% men) and group 2 included patients with CHF without NAFLD (n=240 (71.0 %), 51.6% men). A multivariate regression analysis showed that independent predictors of NAFLD were systolic blood pressure ≥130 mm Hg (odds ratio (OR), 3.700; p <0.001), history of T2DM (OR, 2.807; p <0.005), and waist circumference >111 cm (OR, 2.530; p <0.012). Patients with CAP ≥331 dB/m (S3) had a worse prognosis during the 2-year follow-up for the composite adverse outcome (all-cause mortality + readmission) (Kaplan-Meier curves - Log-Rank p=0.035).Conclusions NAFLD was detected in almost one-third of patients hospitalized for DCHF. AH, T2DM, and abdominal obesity were associated with a high risk of NAFLD. However, only severe steatosis (S3) was an independent predictor of adverse clinical outcomes during a 2-year period after adjustment for known risk factors.

To study the interrelations between the rs4073 polymorphism of the IL-8 gene, IL-8 serum levels and severity of alcoholic hepatitis (AH).

The present work introduces CeO2 nanoparticles as an effective agent for Nonalcoholic fatty liver disease therapy. X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and ultraviolet visible (UV-Vis) spectroscopy techniques were used to characterize CeO2 nanoparticles. Patients with acute coronary syndrome (ACS) after stenting were distributed according to the criterion of the presence and absence of concomitant non-alcoholic fatty liver disease (NAFLD), diagnosed by the European Association for the Study with liver fibroelastometry (with the Controlled Attenuation Parameter function). Patients with FATS are distinguished by a longer duration of stay in the intensive care unit as a result of an increase in the incidence of complications of myocardial infarction (p = 0.048). The values of liver fibrosis in steatosis / steatohepatitis in combination with ACS are inversely related to the TIMI (Thrombolysis in Myocardial Infarction) index, and the degree of elevation of transaminases and gamma glutamyltransferase levels exceeds the values in ACS without NAFLD (p <0.05).

Формирование сердечно-сосудистой патологии при чрезмерном употреблении алкоголя сопряжено с повышением концентрации в крови таких медиаторов воспаления, как интерлейкины 6 (IL6) и 8 (IL8) и хемоаттрактанта моноцитов CCL2 (C-C motif ligand 2), а также молекул, участвующих в функционировании эндотелия, в частности фактора роста сосудистого эндотелия (VEGFA, vascular endothelial growth factor А), молекулы клеточной адгезии (ICAM1, intercellular adhesion molecule 1) и эндотелина (EDN1). Предполагается, что данный процесс генетически детерминирован, однако до настоящего момента исследований в этом направлении не проводилось. Целью работы явилось изучение ассоциации носительства аллелей полиморфных локусов, расположенных в генах IL6 (rs1800795), IL8 (rs4073), CCL2 (rs1024611), VEGFA (rs699947 и rs2010963), ICAM1 (rs281437) и EDN1 (rs1800541) с содержанием соответствующих полипептидов в циркуляторном русле и развитием сердечно-сосудистых заболеваний на фоне хронического злоупотребления алкоголем. В исследование были включены лица, злоупотребляющие алкоголем, без выраженной соматической патологии, а также пациенты, у которых на фоне злоупотребления развились заболевания сердечно-сосудистой системы. Уровень IL6, IL8, CCL2, VEGFA, ICAM1 и EDN1 в сыворотке крови оценивали посредством ИФА. Аллели полиморфных локусов были определены посредством ПЦР в режиме реального времени. Установлено, что среди лиц, злоупотребляющих алкоголем, с клинически выраженной патологией сердечно-сосудистой системы значительно чаще встречаются только носители гомозиготного генотипа GG или аллеля G полиморфного локуса в гене IL6 (rs1800795). Кроме того, носительство генотипа GG повышает вероятность развития сердечно-сосудистых заболеваний при хроническом злоупотреблении алкоголем. Однако, дополнительное влияние оказывают демографические факторы и клинические характеристики пациентов. В частности, введение поправки на возраст и пол, а также учет наличия цирроза печени, гипертензии и сахарного диабета, сопровождающих злоупотребление алкоголем, нивелируют повышение риска патологии сердечно-сосудистой системы. Ассоциации полиморфных вариантов в генах IL6 (rs1800795), IL8 (rs4073), CCL2 (rs1024611), VEGFA (rs699947 и rs2010963), ICAM1 (rs281437) и EDN1 (rs1800541) с содержанием белковых продуктов соответствующих генов в циркуляторном русле выявлено не было. Cardiovascular diseases in alcohol abusers are associated with elevation of plasma levels of proinflammatory cytokines such as IL6, IL8 and CCL2 as well as molecules involved in endothelial functioning including VEGFA, ICAM1 and EDN1. This phenomenon is supposed to be genetically determined. However to date the issue has not been investigated. Thus, we aimed to study the relationship between carriage of SNPs of IL6 (rs1800795), IL8 (rs4073), CCL2 (rs1024611), VEGFA (rs699947 and rs2010963), ICAM1 (rs281437) and EDN1 (rs1800541) genes with the serum levels of their products and the development of cardiovascular diseases in alcohol abusers. The study included alcohol abusers without apparent somatic pathology and alcohol abusers with clinical manifestations of cardiovascular disease. Serum levels of IL6, IL8, CCL2, VEGFA, ICAM1 and EDN1 were estimated by EIA. SNPs were determined by means of real-time PCR. We found that among the SNPs studied only carriers of homozygous GG genotype and G allele of IL6 (rs1800795) were more frequent in alcohol abusers with cardiovascular diseases. Moreover, carriage of homozygous GG genotype of IL6 (rs1800795) increases the probability of development of cardiovascular pathology in alcohol abusers. However, adjustment for age, gender and the presence of liver cirrhosis, hypertension and diabetes mellitus as co-variates eliminates the enhanced risk of cardiovascular pathology. Polymorphisms of IL6 (rs1800795), IL8 (rs4073), CCL2 (rs1024611), VEGFA (rs699947 and rs2010963), ICAM1 (rs281437) and EDN1 (rs1800541) did not determine serum levels of the related polypeptides.

Фиброз печени и его конечная стадия - цирроз являются одной из причин летальных исходов при хронических заболеваниях печени. Алкоголь и его метаболиты вызывают накопление внеклеточного коллагена, приводящего к фиброзу, вследствие цитокинового дисбаланса, процессов фиброгенеза и фибролиза. Цель. Изучить иммуновоспалительные факторы, ассоциации полиморфизма гена коллагена I типа COL1A1_1 C/A (rs1107946) с развитием фиброза печени у пациентов, злоупотребляющих алкоголем. Методика. Генотипировано 46 пациентов с фиброзом печени, злоупотребляющих алкоголем (срок употребления алкоголя 15,6±9,5 лет). Группы сформированы в зависимости от стадии фиброза печени, определенного методом непрямой эластометрии: 1-я - F0+1 (n=20), 2-я - F3+4 (n=36). Критерии исключения: острый алкогольный гепатит, хронические заболевания печени неалкогольного генеза, общие воспалительные и аутоиммунные процессы. У всех больных определяли концентрации интерлейкина (ИЛ)-6, ИЛ-8, ФНО-альфа, VEGF-A, s-ICAM-1, ЭТ-1. Полиморфизм гена COL1A1_1 определяли методом Real-Time PCR. В качестве контрольной группы полиморфизма гена коллагена были обследованы 30 здоровых мужчин и женщин. Результаты. Уровни ИЛ-6, ИЛ-8, s-ICAM-1, ET-1 зависили от степени алкогольного фиброза печени: во 2-й группе они были выше, чем в 1-й (p<0,05). Плотность печени статически значимо (p<0,05) коррелировала с уровнем ИЛ-6 (r=0,6), ИЛ-8 (r=0,77), s-ICAM-1 (r=0,58), ET-1 (r=0,56). Cтатически значимых различий уровней ФНО-альфа и VEGF-A между группами не выявлено (р>0,05). У больных с фиброзом печени, страдающих алкогольной зависимостью, частота встречаемости аллеля А статически значимо выше, чем в контрольной группе (38,3% против 12,5%, χ2 = 7,6212; р=0,005768). Частота гетерозигот СА существенно не отличается в группе больных и контрольной группе (38% и 25% соответственно, р=0,4425). Гомозиготы АА были выявлены только в группе больных с фиброзом печени, частота встречаемости составила 19,1%. Заключение. Выявлена прямая корреляционная связь между уровнем цитокинов (IL-8, IL-6), молекул эндотелиальной дисфункции (EТ1, sICAM-1) с уровнем фиброза печени. Наличие аллеля А гена COL1A1_1 может являться одним из генетических факторов развития фиброза печени у больных, злоупотребляющих алкоголем. Liver fibrosis and its final stage - cirrhosis is one of the causes of deaths in chronic liver diseases. Alcohol and its metabolites mediate the accumulation of extracellular collagen, leading to fibrosis mediated by cytokine imbalances, processes of fibrogenesis and fibrolysis. The purpose. To investigate the immune-inflammatory factors and association between the COL1 A1_1 C/A (rs1107946) polymorphism and liver fibrosis in patients abusing alcohol. Мethods. 46 patients were genotyped (the period of alcohol consumption was 15.6±9.5 years) with liver fibrosis, alcohol abusers. They were divided into 2 groups depending on the stage of liver fibrosis: 1- F0+1, n=10; 2- F3+4, n=36. Exclusion criteria were chronic non-alcoholic liver disease, acute alcoholic hepatitis, general inflammatory and autoimmune diseases. We analyzed serum concentrations of interleukin (IL)-6, IL-8, TNF-α, VEGF-A, s-ICAM-1, ET-1 and polymorphism of the COL1A1_1 gene was determined using the Real-Time PCR analysis. The stage of liver fibrosis was identified with the elastography method (FibroScan, Echosens, France). Results. The levels of IL-6, IL-8, s-ICAM-1, ET-1 depended on the degree of alcoholic liver fibrosis. The liver fibrosis was significantly correlated with the level of IL-6 (r = 0.6), IL-8 (r = 0.77), s-ICAM-1 (r = 0.58), ET- 1 (r = 0.56) (p <0.05). There were no significant differences in the levels of TNF-alpha and VEGF-A between two groups (p> 0.05). It was found that the frequency of allele A among patients was 38.3% which is significantly higher than in the control group (12.5%; р=0.005768). The frequency of heterozygotes CA was not significantly different between the group of patients and the control group (38% and 25% respectively, p = 0.4425). Homozygous AA genotypes were revealed only in patients with liver fibrosis, the frequency was 19.1%. Conclusion. A positive correlation between the level of cytokines (IL-8, IL-6), endothelial dysfunction molecules (ET1, sICAM-1) and the level of liver fibrosis was revealed. The presence of allele A of the COL1A1_1 gene may be one of the genetic factors involved in the development of liver fibrosis in patients abusing alcohol.

Objective: To evaluate structural and functional cardiac changes in patients with alcoholic cirrhosis in relation to the severity of liver disease. Methods: Study included 80 patients with alcoholic liver cirrhosis (LC) without history of cardiovascular and respiratory disease. ECG, echocardiography were performed. Plasma values of NT-proBNP were evaluated in 60 patients. Results: Left ventricular ejection fraction was normal in all patients (mean value 65,3 ± 5,8%). Left ventricular hypertrophy (LVH) (LVMI 149,8 ± 20 g/m 2) and LV diastolic dysfunction were observed in 33 (40,7%) and 58 (71,6%) patients, respectively. Median NT-proBNP value was 621,5 pg/ml (min 33 pg/ml; max 3849 pg/ml), NT-proBNP elevation (> 125 pg/ml) was observed in 47 (58%) patients. NT-proBNP level positively correlated with the number of points on the Child-Pugh score (R =0,27, p < 0,05). There was no relationship between the severity of cirrhosis and structural and functional cardiac changes. Conclusion: Patients with alcoholic LC frequently demostrate structural and functional cardiac changes such as left ventricular hypertrophy, diastolic dysfunction. NT-proBNP elevation was observed in more than half of the patients and directly correlated with the severity of cirrhosis.

The aim of study was to detect the genetic factors which cause the predisposition for alcoholic liver damage. The main candidate genes of high risk are isoforms of adh and aldh genes which are responsible for different rate of alcohol metabolism and oxidation of ethanol and acetaldehyde. Our results demonstrated that allelic variant adh 2-2 is in a higher frequency in patients with alcoholic liver damage than in a population (16% vs. 7%; p < 0,05). The polymorphism t 174 m of angiotensinogen gene AGT was studied as risk factor of alcoholic liver damage. The allelic variant т of angiotensinogen gene AGT is more frequent (15,8%) in patients with alcoholic liver cirrhosis and alcohol abuse without cirrhosis (n = 98) than in a population (6,7%, n = 52; p = 0,04). the greater frequency of allele m was in a group with alcoholic liver cirrhosis (17,3%; p = 0,058). Our. data provides the evidence that polymorphism t 174 m of AGT gene does not influence the progression (clinical picture) of alcoholic liver cirrhosis, except the level of GGT, which is increased in patients with homozygous genotype tt.

Aim: to detect the genetic factors predisposing alcoholic liver lesion. The main candidate genes of high risk are isoforms of adh and aldh genes which are responsible for different level of alcohol metabolism and oxidation of ethanol and acetaldehyde. Our results demonstrated that allelic variant adh2-2 is observed more frequently in patients with alcoholic liver damage than in population (16% vs. 7%; p t174m of angiotensinogen gene AGT was investigated as one of the risk factor of alcoholic liver lesion. The allelic variant m of angiotensinogen gene AGT is more frequent (15.8%) in patients with alcoholic liver cirrhosis and alcohol abuse without cirrhosis (n = 98) than in population (6.7%, n = 52; p = 0.04). The highest frequency of allele m was in a group with alcoholic liver cirrhosis (17.3%; p = 0.058). Our data provides the evidence that polymorphism t174m of AGT gene does not influence the progression (clinical picture) of alcoholic liver cirrhosis, except the level of GGT, which is increased in patients with homozygous genotype tt.