Актуальним є дослідження проблеми забезпечення реальної, а не декларативної незалежності судової влади в Україні, що набуває особливої ваги в умовах повномасштабної збройної агресії російської федерації та реалізації стратегічного курсу на європейську інтеграцію. Стаття висвітлює проблему недостатньої ефективності існуючих кримінально-правових та процесуальних механізмів протидії втручанню в діяльність суддів. Автор наголошує, що лише неупереджений та безсторонній суд здатен виконати своє головне завдання – здійснення правосуддя, а будь-який незаконний вплив на суддів підриває основи правової держави та довіру суспільства до системи правосуддя.У статті обґрунтовується необхідність комплексного підходу до захисту суддівської незалежності, що має поєднувати як норми матеріального, так і процесуального права. Методами дослідження були формально-юридичний, що дозволив проаналізувати положення Конституції України, Кримінального та Кримінального процесуального кодексів, законів України «Про судоустрій і статус суддів» та «Про Вищу раду правосуддя»; системно-структурний, який застосовувався для вивчення системи гарантій незалежності суддів як єдиного цілого; а також метод аналізу наукової доктрини та емпіричних даних, зокрема звітів Вищої ради правосуддя, що дало змогу виявити типові форми втручання та проблеми правозастосування.У статті аналізується склад кримінального правопорушення, передбаченого статтею 376 КК України «Втручання в діяльність судових органів», зокрема його об'єкт, об'єктивна та суб'єктивна сторони, суб'єкт та потерпілий. Автор статті вважає, що чинна редакція цієї норми є неповною та потребує вдосконалення. Особлива увага приділяється поняттям «правосуддя» та «втручання», а також аналізу процесуальних гарантій, серед яких ключова роль відводиться Вищій раді правосуддя, інституту відводу (самовідводу), заходам безпеки щодо учасників судочинства та потенціалу діджиталізації правосуддя, зокрема функціонуванню Єдиної судової інформаційно-комунікаційної системи. У роботі зроблено висновок, що ефективна протидія тиску на суд можлива лише за умови синергії надійних кримінально-правових заборон та дієвих процесуальних механізмів, адаптованих до сучасних викликів, зокрема воєнного стану. Встановлено доцільність розширення кола потерпілих від втручання та посилення відповідальності за такі діяння, вчинені спеціальними суб'єктами. Автор пропонує власні пропозиції щодо вдосконалення кримінального та процесуального законодавства, спрямовані на створення більш надійного правового щита для захисту незалежності судової влади в Україні.

The current understanding of the role of non-coding RNAs in the regulation of signaling pathways that control lipid accumulation and the development of inflammation in non-alcoholic fatty liver disease (NAFLD) is outlined. The contribution of peroxisome proliferator-activated receptors (PPARs) to changes in lipid metabolism and the formation of lipotoxicity as trigger mechanisms of NAFLD is considered. The role of TGFβ, TNFα/NF-κb, IL-6/JAK/STAT3 signaling pathways in the activation of stellate cells, liver fibrogenesis and the progression of NAFLD has been demonstrated. Analysis of literature data has revealed a number of microRNAs and long non-coding RNAs (lncRNAs) presumably associated with the regulation of these signaling pathways in this disease. They may probably have prognostic significance for differentiating clinical forms and severity of NAFLD.

The CD39/CD73/adenosine signaling pathway is currently of therapeutic interest, especially in cancer. Many enzymes are involved in the metabolism of adenosine. Adenosine kinase is an enzyme that catalyzes the formation of AMP from adenosine. Due to the removal of adenosine from the transmethylation reaction, the long isoform of adenosine kinase is considered as an epigenetic regulator. Aberrant methylation in carcinogenesis is a frequent phenomenon, but the role of ADK-L in cancer is poorly understood. The aim of the present study was to evaluate the relationship between the ADK-L gene expression levels and levels of immune and adenosinergic genes (FOXP3, RORC, CD39, CD73, and A2AR) and methylation levels of APC, SEPT9, TSDR-FOXP3 genes in colon tissue of patients with colorectal cancer (CRC). Gene expression was evaluated by qRT-PCR in normal and CRC tumor tissue. Promoter methylation of the APC and SEPT9 genes and the TSDR region of the FOXP3 gene was evaluated by methylation-sensitive high resolution melting analysis (MS-HRM). It was shown that CRC tumors exhibited demethylation of the TSDR region of the FOXP3 gene (p = 0.0056) and increased promoter methylation of the SEPT9 gene (p = 0.002). No correlation was found between the ADK-L gene expression and the level of methylation of SEPT9, APC, and TSDR-FOXP3 genes. Statistically significant associations were found between the expression of genes involved in the CD39/CD73/A2AR signaling pathway and the immune transcription factor genes FOXP3 and RORC. It has been shown that there is a close correlation between the expression of immune genes and adenosinergic pathway genes. This highlights their importance as immune checkpoints in cancer.

Purpose: Comparative analysis of the expression level of long non-coding RNAs MALAT1, GAS5, DANCR, TUG1 in peripheral blood leukocytes (PBL) of healthy people and patients with NAFLD (liver steatosis, NASH of varying activity, liver cirrhosis). Materials and methods: We examined 106 patients diagnosed with NAFLD for the first time: 31 patients with liver steatosis (LS), 64 patients with weak (WA), moderate (MA) and high (HA) NASH activity and 11 patients at the stage of liver cirrhosis (LC). The control group consisted of 30 healthy donors. The mRNA level of the TUG1, DANCR, MALAT1, GAS5 genes in PBL was determined by RT-PCR. Results: A higher level of expression of the TUG1 gene was registered in the PBL of patients with NASH-WA compared to LS, and a tendency was revealed to increase the level of TUG1 mRNA in the PBL with increasing NASH activity, which indicates the possibility of using the level of TUG1 expression in the PBL as a minimally invasive diagnostic (to distinguish between LS and NASH-WA) and a prognostic marker (with the progression of NAFLD). Analysis of the expression level of lncRNA MALAT1 showed no significant differences between all studied groups. Results were obtained indicating complex dynamics of the GAS5 expression level: the level of transcripts increases during the formation of liver steatosis and then decreases during the transition to NASH. It was shown that the level of DANCR expression in the PBL of patients with NASH-WA is significantly lower than in patients with liver steatosis and NASH-MA. Conclusion: New data were obtained on the expression level of the MALAT1, GAS5, DANCR, TUG1 lncRNAs in the PBL of patients with NAFLD, indicating the possibility of using the level of TUG1 expression in the PBL as a minimally invasive diagnostic and prognostic marker in NAFLD. It has also been shown that the level of DANCR mRNA in PBL may have some diagnostic value in distinguishing between LS and NASH-WA.

The levels of NO metabolites in the plasma and mRNA of the NOS3, ATG9B, and NOS2 genes in peripheral blood leukocytes of healthy people and patients with early forms of non-alcoholic fatty liver disease (steatosis and weak activity non-alcoholic steatohepatitis) were studied. In patients with steatohepatitis, the concentration of NO metabolites in the blood and the level of mRNA of the NOS2 gene were higher than in patients with steatosis and healthy people. These differences can be of diagnostic value for distinguishing between steatosis and weak activity steatohepatitis in non-alcoholic fatty liver disease. A correlation between the levels of NO metabolites and the expression of the NOS2 gene in weak activity steatohepatitis was established, which indicates activation of NO synthesis in non-alcoholic steatohepatitis due to the expression of the inducible NO synthase gene. The level of the NOS2 gene mRNA in peripheral blood leukocytes of patients with weak activity steatohepatitis correlated with the level of TNFα and IL-6 cytokines. An increase in the level of NO in the blood in weak activity steatohepatitis correlated with the level of MDA, an indicator of oxidative stress.

The aim of the study was to determine the clinical and diagnostic significance of collagens of the third type (Col3) and the fourth type (Col4) in various forms of alcoholic liver disease (ALD). Materials and methods. 98 patients with ALD were examined: 13 (13.3%) with liver steatosis (LS), 15 (15.3%) with steatohepatitis (SH), 56 (57.1%) with liver cirrhosis (LC), 14 (14.3%) with severe alcoholic hepatitis against the background of liver cirrhosis (SAH-LC). Among the examined there were 59 (60.2%) men and 39 (39.80%) women, the average age was 53.48±11.45 years. The content of fibrogenesis proteins in the blood serum - type III collagen (Col3) and type IV collagen (Col4) was determined by enzyme immunoassay (test systems "Kit For Collagen Type III (Col3)" and "Kit For Collagen Type IV (Col4)", "Cloud-Clone Corp", USA), a marker of hepatocyte apoptosis - fragments of cytokeratin-18 (FCK-18) ("Biotech" test system, Sweden), cytokines - IL-1β, IL-4, IL-6, IL- 8, TNF-α ("Vector-Best", Russia). Results. The level of Col3 in healthy individuals was 6.12±0.73 ng/ml and Col4-9.45±0.32 ng/ml. In all forms of ALD, the content of both types of collagen exceeded that in healthy individuals: Col3 in LS was 6.52±0.94 ng/ml (p<0.05), in SH it was 12.50±3.18 ng/ml (p<0.05), in LC - 20.96±4.93 ng/ml (p<0.05), in SAH-LC - 26.90±3.87 ng/ml (p<0.05); Col4-10.14±0.66 ng/ml, 13.87±1.15 ng/ml, 79.56±33.10 ng/ml and 107.12±39.09 ng/ml, respectively. Col3 positively correlated with ALT (r=0.27, p=0.02) and alkaline phosphatase (r=0.28, p=0.04). Col4 correlated with bilirubin (r=0.74), AST (r=0.65), glutamyl transpeptidase (r=0.58), cytokeratin-18 (r=0.56), sedimentation rate of erythrocytes (r=0.61), C-reactive protein (r=0.59), IL -6 (r= 0.51) and leukocytes (r=0.45) (all p<0.001). Conclusion. Col4 demonstrated greater diagnostic and clinical significance in alcoholic liver disease compared to Col3. The level of Col4 increased by an average of 8 times with the progression of the disease from liver steatosis to cirrhosis, and Col3 - only by 3 times. There were more diverse and stronger associations between Col4 and markers of hepatocellular damage and inflammation than between Col3 and these indicators. The maximum rise in the levels of both types of collagen found in SAH-LC confirmed the important role of this form of liver disease in the development of fibrosis, and hence in the further decompensation of liver cirrhosis.

Objective. The aim of the study was to evaluate the level of expression of the NOS2, NOS3, SONE genes in peripheral blood leukocytes (PBL) of patients with hypertension (HTN) and to study the relationship between the level of transcripts of these genes and the content of nitric oxide metabolites and markers of endothelial dysfunction.Design and methods. The study included healthy people (25 people) and patients with HTN (stages I–II) before prescribing antihypertensive drugs (15 people) and taking cardioselective β-adrenergic receptor blockers for more than a year (metoprolol (25 mg per day) or bisoprolol (5–10 mg per day)) (20 people). The level of gene transcripts was assessed by real-time polymerase chain reaction (PCR). The level of nitric oxide metabolites was determined by the colorimetric method using the Griess reagent. The content of asymmetric dimethylarginine (ADMA), soluble forms of vascular cell adhesion molecule (sVCAM), and intercellular adhesion molecule (sICAM) in blood plasma was determined by ELISA. The content of malondialdehyde (MDA) in blood plasma was determined spectrophotometrically by color reaction with thiobarbituric acid. Statistical processing of the results was carried out using the Statgraphics Centurion XVI software package (version 16.1.11).Results. The level of nitric oxide metabolites in the blood plasma of HTN patients without antihypertensive therapy was 2,1 times higher than in healthy individuals (p = 0,001) and 1,7 times higher than in patients with HTN taking metoprolol or bisoprolol (p = 0,002). The relative content of mRNA of the NOS3 gene in PBL of individuals included in the study did not differ (p > 0,05). The level of NOS2 gene transcripts in PBL of HTN patients before the prescription of antihypertensive drugs exceeded that in healthy individuals (p = 0,0009) and in HTN patients taking metoprolol or bisoprolol (p = 0,0002). The number of SONE transcripts in the PBL of HTN patients was higher than in people with normal blood pressure (p < 0,00001 when comparing patients before the prescription of antihypertensive therapy and individuals from the control group; p = 0,04 when comparing patients with HTN taking antihypertensive drugs and normotensive subjects). The content of MDA, ADMA, sVCAM was higher in the plasma of HTN patients without antihypertensive therapy compared with people from the control group (p = 0,005, 0,003, 0,039, respectively) and patients taking metoprolol or bisoprolol (p = 0,0006, 0,019, 0,016, respectively). The content of nitric oxide metabolites positively correlated with NOS2, SONE, VCAM1 mRNA level in PBL, the content of MDA and ADMA in blood plasma (p < 0,05). A positive correlation was found between the concentration of MDA and ADMA in plasma (p = 0,03).Conclusions. An increase in the level of nitric oxide metabolites in HTN is associated with an increase in the transcriptional activity of the NOS2 gene, a disturbance of the redox balance of the body, and the development of endothelial dysfunction. The SONE gene is probably involved in the modulation of nitric oxide levels in HTN not only as an antisense transcript that destabilizes the mRNA of the NOS3 gene in vascular endothelial cells, but also indirectly, namely, through the regulation of homeostasis of immune system cells through autophagy.

The blood level of soluble IL-6 receptor was measured in patients with different clinical and morphological forms of nonalcoholic fatty liver disease and healthy donors. The relationship of the soluble IL-6 receptor with the content of IL-6, the level of the IL6 gene mRNA, and a number of markers of hepatocyte and peripheral blood leukocyte apoptosis was assessed. It has been established for the first time that progression of nonalcoholic fatty liver disease is associated with changes in the level of soluble IL-6 receptor in the blood. In patients with high activity of nonalcoholic steatohepatitis and liver cirrhosis, the blood concentration of soluble IL-6 receptor sharply decreased in comparison with the earlier stages of progression of nonalcoholic fatty liver disease (liver steatosis, nonalcoholic steatohepatitis of weak and moderate activity). This allows considering the decrease in this indicator as a new diagnostic marker for distinguishing nonalcoholic steatohepatitis of high activity from weak and moderate activity. A close correlation between changes in the level of soluble IL-6 receptor and apoptosis of peripheral blood leukocytes and hepatocytes was revealed.

Introduction. The feasibility and risks of glucocorticosteroids (GCS) in severe alcoholic hepatitis (SAH) are actively discussed, and there is a real need to develop new biomarkers both to determine indications for the GCS use and to evaluate their effectiveness. Аim. Тo evaluate the effectiveness of GCS in SAH using a marker of hepatocyte apoptosis and inflammatory cytokines along with traditional laboratory parameters. Materials and methods. Prednisolone at a dose of 40 mg per day was received by 68 patients with SAH. The effectiveness of therapy was assessed after 7 days by the Lille index, the level of cytokeratin-18 fragments (FCK-18) and cytokines – IL-1β, TNF-α, IL-6 and IL-8. Results. A positive effect of GCS was noted in 50 (73.5%) patients, after 7 days the Lille index was 0.23 ± 0.09, the levels of FCK18, IL-6, IL-8, TNF-α were significantly reduced, with subsequent decrease and improvement in hepatic functional parameters. These patients had a 100% short-term (within 28 days) survival rate. Eighteen (26.5%) patients had a negative result, the Lille index was 0.61 ± 0.11, there was no significant decrease in FCK-18 and cytokines. After GCS was discontinued, they developed liver failure, 1/3 developed bacterial infections, all patients died of multiple organ failure within 28 days. Conclusion. The short-term effect of GCS therapy in SAH patients was 73.5%. Along with the traditional Lille index, the following indicators demonstrated diagnostic significance: fragments of cytokeratin-18, cytokines IL-6, IL-8, and, to a lesser extent, TNF-α and IL-1β.

Acute-on-chronic liver failure (ACLF) of varying grades was assessed in 110 patients with alcoholic liver cirrhosis using the on-line CLIF-C ACLF Calculator ( www.efclif.com/scientific-activity/score-calculators/clif-c-aclf ); fragments of cytokeratin-18, TNFα, IL-1β, IL-4, IL-6, and IL-8 were also assayed. As ACLF progressed from grade 0 to grade 3, the levels of cytokeratin-18 fragments, IL-6, and IL-8 significantly increased, while IL-4 decreased. TNFα peaked in ACLF grade 1, but decreased in grades 2 and 3. IL-1β did not depend on the ACLF grade. Thus, hepatic damage and immune dysfunction are implicated in the progression of ACLF.

Arterial stiffness indicators (reflected wave propagation time (RWTT), aortic pulse wave velocity (PWV), arterial stiffness index (ASI), augmentation index (AIx)) were assessed in healthy people and patients with arterial hypertension with different allelic variants of the NOS2 gene (rs1730017 (C>T), rs1800482 (G>C)). We examined healthy individuals (64 people, age 38.58 ± 2.19 years, 28 men and 36 women) and patients with AH (stage I-II) (36 people, age 38.04 ± 1.20 years , 20 men and 16 women). In the group of patients with AH, differences in ASI values between carriers of the T allele and CC genotype of rs1730017 (p = 0.036) and daily average AIx, AIx daily values in individuals with GG and GC + CC genotypes rs1800482 (G> C) were revealed (p = 0.049, p = 0.017, respectively). In the group of healthy people, a significant increase in daily AIx was found in carriers of the C allele at rs1800482 (p = 0.048). Carriage of the T allele by rs1730017, for which a protective effect on the development of AH has been previously shown, causes lower values of the arterial stiffness index in patients with this disease. The presence of the C allele of by rs1800482 in the genotype of healthy and sick people, associated with an increased risk of hypertension, is probably one of the reasons for the increase in AIx, as one of the indicators of arterial stiffness.

Целью исследования явилась сравнительная оценка уровня медиаторов врожденного иммунитета у пациентов с простой декомпенсацией алкогольного цирроза печени (АЦП) и с острой на хроническую печеночную недостаточность (ОХПН). Материалы и методы. Обследовано 115 пациентов с АЦП: 46 (40,0%) - с простой декомпенсацией АЦП, 69 (60,0%) - с признаками ОХПН, то есть с наличием полиорганной недостаточности (печеночной, почечной, мозговой, дыхательной, циркуляторной или коагуляционной). Наличие ОХПН оценивалось с помощью online-калькулятора (https://www.clifresearch.com/ToolsCalculators.aspx). Методом иммуноферментного анализа определялись цитокины: ТНФα, ИЛ-1β, ИЛ-6, ИЛ-8 («Вектор-Бест», Россия). Для статистического анализа использовалась программа Statgraph 2.1 (Statistical Graphics Corp., США). Результаты. У пациентов с ОХПН достоверно и многократно были выше уровни цитокинов ИЛ-6, ИЛ-8, ТНФα наряду с увеличением всех основных функциональных печеночных тестов, уровня креатинина, степени энцефалопатии по сравнению с таковыми показателями у пациентов без ОХПН. Уровень ИЛ-1β повышался недостоверно. Заключение. Определение в крови медиаторов врожденного иммунитета ИЛ-6, ИЛ-8 и ТНФα целесообразно использовать для диагностики цитокинового шторма и прогноза развития ОХПН при острой декомпенсации АЦП.

Цель. Оценка печеночно-клеточного повреждения и иммунного воспаления при разных формах алкогольной болезни печени (АБП). Материалы и методы. Обследованы 104 больных АБП: 15 (14,4%) стеатозом печени (СП), 19 (18,3%) стеатогепатитом и 70 (67,3%) циррозом печени (ЦП); мужчин 50 (48,1%), женщин 54 (51,9%); возраст – 45,7±8,4 года. Выполнялись традиционные клинико-лабораторные, инструментальные исследования, иммуноферментным анализом определялись уровни фрагментов цитокератина-18 (ФЦК-18), цитокинов – интерлейкина (ИЛ)-1â, фактора некроза опухоли a (TNF-a), ИЛ-4, ИЛ-6, ИЛ-8. Контрольную группу составили 39 здоровых лиц: мужчин – 20 (51,2%), женщин – 19 (48,7%), возраст – 48,5±8,3 года. Результаты. При СП отмечалось увеличение уровня ФЦК-18 при нормальной активности аминотрансфераз, увеличивалось содержание TNF-a, ИЛ-6, ИЛ-1â, ИЛ-8 и снижался уровень ИЛ-4 по сравнению с таковыми у здоровых лиц. При стеатогепатите отмечались трехкратный по сравнению со СП рост аминотрансфераз и ФЦК-18, а также увеличение уровня медиаторов воспаления, в большей степени – ИЛ-6, в меньшей степени – ИЛ-8, TNF-a, снижение ИЛ-4, ИЛ-1â сохранялся на том же уровне. При ЦП фиксировался дальнейший рост ФЦК-18, достоверно более выраженный, чем увеличение аспартатаминотрансферазы, и продолжалось увеличение цитокинов – в одинаковой степени уровня ИЛ-6 и ИЛ-8, в меньшей степени – ИЛ-1â и TNF-a, снижался уровень ИЛ-4. Заключение. При прогрессировании АБП от СП до стеатогепатита печеночно-клеточное повреждение осуществлялось в одинаковой степени выраженными процессами некроза и апоптоза гепатоцитов, при развитии ЦП повреждение паренхимы происходило преимущественно за счет апоптоза гепатоцитов. Иммуновоспалительный процесс прогрессивно нарастал от стадии СП до ЦП, наибольшую динамику при этом претерпевали ИЛ-6 и ИЛ-8. ФЦК-18 могут служить неинвазивным маркером печеночно-клеточного повреждения, а ИЛ-6 и ИЛ-8 – маркерами иммунного воспаления при АБП.

The aim of the study was to assess the pathogenetic, diagnostic and clinical role of tissue molecular pathogens – fragments of cytokeratin-18 in the development of acute chronic liver failure (ACLF) in decompensated alcoholic liver cirrhosis (ALC).Materials and methods. 80 patients with ALC were examined: 30 without signs of ACLF and 50 with signs of ACLF and 36 healthy individuals. Hepatic functional tests were determined, a marker of hepatocyte apoptosis – fragments of cytokeratin-18 (FCK-18) (Biotech, Sweden) by the enzyme immunoassay, ACLF scores were calculated using an on-line calculator at www.efclif.com/scientific-activity/score-calculators/ clif-c-aclf.Results. With ACLF, a high level of FCK-18 was detected – 1505.4 ± 446.9 U/L, more than 20 times higher than that in healthy individuals – 71.5 ± 19.6 U/L (p < 0.05) and three times higher than the level of FCK-18 in patients with ALC without ACLF – 489.4 ± 490.2 U/L. The levels of aminotransferases, bilirubin, creatinine, INR were significantly higher in patients with ACLF compared with patients without ACLF, and the level of albumin was lower. FCK-18 level directly correlated with ALT – r = 0.61 (p < 0.05), AST – r = 0.68 (p < 0.05), with bilirubin level – r = 0.41 (p < 0, 05) and the ACLF score – r = 0.48 (p < 0.05) and inversely correlated with the albumin level r = –0.51 (p < 0.05).Conclusion. Apoptosis of hepatocytes and tissue molecular pathogens released during it – fragments of cytokeratin-18 – play a role in the development of acute chronic liver failure in decompensated alcoholic liver cirrhosis.

We examined 74 patients with acute decompensation of alcoholic liver cirrhosis: 34 (45.9%) with bacterial infection (group 1) and 40 (54.1%) without bacterial infection (group 2). The degree and index of acute-on-chronic liver failure (ACLF) were determined using an on-line CLIF-C ACLF Calculator and the levels of cytokeratin-18 fragments, TNFα, IL-1β, IL-4, IL-6, and IL-8. In group 1, AST, cytokeratin-18, TNFα, IL-1β, IL-6, degree and score of ACLF were significantly higher than in group 2. ACLF developed in 18 (52.9%) patients in group 1 and in 11 (27.5%) (p<0.05) patients in group 2. Within 1 month, 10 (29.4%) patients of group 1 and 2 (5%) patients of group 2 died (p<0.05). Patients with bacterial infection showed a more severe course of alcoholic liver cirrhosis and ACLF than those without bacterial infection.

Introduction. NAFLD is an urgent health problem, its prevalence reaches 45%. NAFLD increases the risk of cardiovascular diseases by 3 times, the risk of death from them by 2 times and increases the risk of developing diabetes by 5 times. NAS occupies up to 20% of the structure of NAFLD and has a high potential for progression, and the violation of endogenous glycemic regulation and the development of DM2 accelerates the rate of disease progression.The goal was to determine the frequency of development of prediabetes (PD) and type 2 diabetes mellitus (T2DM) in NASH patients and the effect of impaired glycemic status on the clinical features of NASH.Materials and methods: 211 NASH patients were examined: 148 (70.1%) men, 63 (29.9%) women, 48.3 ± 10.2 years old. The diagnosis was established on the basis of clinical, laboratory, ultrasound and histological data. By enzyme immunoassay were determined: TNF-α, cytokeratin-18 fragments (CKF-18), insulin; were calculated HOMA-IR and NAFLD fibrosis score (NAFLD FS).Results and discussion. PD was detected in 39 (18.5%) patients, T2DM - in 33 (15.6%) patients. In PD patients, in contrast to patients with normoglycemia, the following indicators were significantly higher: waist circumference (WC), body mass index (BMI), cholesterol levels (Ch), LDL, ESR, TNF-α, NAFLD FS and lower albumin and platelet levels. In patients with T2DM, in contrast to those with normoglycemia, the following indicators were significantly higher: WC, BMI, alanine aminotransferase, alkaline phosphatase (APh), Ch, ESR, CKF-18 and NAFLD FS. In T2DM patients in contrast to those with PD, the following indicators were significantly higher: aminotransferases, APh and lower albumin level.Conclusions. Prediabetes and T2DM were detected with almost the same frequency among patients with NASH – in 18.5% and 15.6%, respectively. Disturbance of glycemic status was associated with a significance increase in waist circumference, markers of inflammation, dyslipidemia, fibrosis, hepatocytic necrosis, apoptosis, intrahepatic cholestasis and a decrease in albumin level.

The goal. To determine the value of the triglyceride glucose index (TGI) for the diagnosis of insulin resistance (IR) in early forms of non-alcoholic fatty liver disease (NAFLD).Materials and methods. 99 patients with NAFLD were examined: 38 (38.4%) with liver steatosis (LS) and 61 (61.6%) with steatohepatitis (SH). TGI was determined by the formula — In [fasting TG (mg / dl) × fasting glucose (mg / dl) / 2], patients with LS and SH were divided into quartiles (Q1-Q4) by increasing TGI levels with an assessment of liver tests, insulin levels (“Insulin TEST System”, Monobind Inc., USA), HOMA-IR, fragments of cytokeratin-18 (FCK-18) ("TPS ELISA, Biotech”, Sweden) and TNF-α (“Human TNFα Platinum” ELISA, eBioscience, Austria).Results. In patients with LS with a TGI increase from Q1 to Q4, HOMA-IR increased from 1.12 ± 0.48 to 6.02 ± 3.15 (p <0.05), a direct relationship was found between these indicators — r = 0.52 (p = 0.03). TGI also correlated with waist circumference — r = 0.81 (p = 0.01), cholesterol — r = 0.51 (p = 0.002), alkaline phosphatase — r = 0.41 (p = 0.02). In patients with SH, from Q1 to Q4, HOMA-IR increased from 3.15 ± 1.8 to 6.2 ± 3.04 (p <0.05), but there was no significant correlation between HOMA-IR and TGI. The levels of FCK-18 increased from Q1 to Q4-139.82 ± 72.45 to 359.75 ± 189.03 U / L (p <0.05) and TNF-α — from 6.38 ± 1.25 pg / ml up to 7.75 ± 1.09 pg / ml (p <0.05). There was a connection between TGI and the level of a marker of hepatocyte apoptosis — FCK-18 — r = 0.43 (p = 0.004).Conclusion. In liver steatosis, TGI has demonstrated its diagnostic role as a surrogate marker of insulin resistance, correlating with HOMA-IR. In steatohepatitis, TGI reflected the degree of hepatocytic apoptosis, correlating with fragments of cytokeratin-18.