Fixed-dose drug products as well as non-fixed hepatoprotective drug combinations are commonly used in modern clinical practice. Combined and concurrent drug use makes it possible to augment the pharmacological effects of individual agents, or extend the range of their potential indications. The drugs most commonly considered for combination therapy include essential phospholipids, glycyrrhizinic acid, ursodeoxycholic acid, silibinin, and S-adenosylmethionine. This paper discusses the rationale for combined use of liver-targeting drugs from a pathogenetic viewpoint, and provides a review of the evidence from clinical trials on combined pharmacotherapy for liver disease.

Human placenta hydrolysates (HPH) have a pronounced hepatoprotective effect, the molecular mechanisms of which are not well understood. As a result of de novo mass spectrometric sequencing and bioinformatics analysis of peptides, 27 peptides were found in the Laennec HPP preparation, which (1) support inositol phosphate-dependent signaling pathways of hepatocytes, (2) activate the target proteins RARA, AMPK, and (3) inhibit target proteins Notch1, GSK-3, PAK1 and TLR4. By exhibiting anti-inflammatory, antifibrotic, vasodilatory, antiatherosclerotic, and antidiabetic properties, these peptides can make a significant contribution to the hepatoprotective properties of HLP.

The aim. To evaluate the diagnostic characteristics of the calculated APRI indices and the liver cirrhosis classifier (CCP) to determine the class of liver cirrhosis. Materials and methods. The study involved 53 patients with cirrhosis of the liver of different etiologies (32 men and 21 women) with an average age of 53.2 ± 5.86 years, of which 22 people (41%) had an alcoholic genesis of the disease, 21 patients (40%) - viral (in the outcome of HCV), 10 patients (19%) had a mixed etiology of cirrhosis (alcohol + hepatitis C virus). The control group included 10 practically healthy individuals. The activity of aspartate aminotransferase (AST), the concentration of total bilirubin (OB), albumin, the number of platelets and the time of activated partial thromboplastin time (APTT) were determined in the blood. To assess the severity of the patients’ condition and the class of liver cirrhosis, the Child-Pugh classification was used, the presence and severity of ascites were determined by ultrasound. The APRI index was calculated using the formula: APRI = (AST / (upper limit of AST)) × 100 / platelets (10⁹/l), where the upper normal AST value was 34 units/l. The CСР index was determined using the formula: CPR = 1.4328 + 0.0014 x AST + 0.00008 x ОВ x 0.0771 x ALBUMIN + 0.0721 x AРТТ. Results. With values of the APRI index less than 0.38 and the CСР index less than 0.5, cirrhosis with a sensitivity of 100% and a specificity of 80-90% is excluded. With an APRI value from 0.8 to 1.5 and a CСР from 0.5 to 1.4, patients are diagnosed with class A liver cirrhosis, the intervals of 1.5 ≤ APRI ≤ 2.0 and 1.5 ≤ CСР ≤ 2.4 correspond to class B cirrhosis, and the values of the APRI indices ≥2.0 and CСР ≥ 2.5 correspond to class C. Conclusion: the calculated APRI and CСР indices are minimally invasive, easy to perform, include a small list of inexpensive and affordable laboratory tests, have good diagnostic characteristics, therefore they can be used in clinical practice to exclude liver cirrhosis and objectively assess the severity of the disease in order to timely conduct adequate drug therapy in patients.

Rpose of the study. To study the relationship between fatal cardiovascular events and non-alcoholic fatty liver disease (NAFLD) among the population of the Irkutsk region. Materials and methods. The study was conducted on the basis of the Irkutsk Regional Bureau of Forensic Medicine. The object of the study was the medical documentation - “The autopsy report”. Results. To study the possible relationship, a retrospective analysis of the results of 2220 autopsies performed over 3 years was carried out: 2010-2012. in the pathological department. Signs of non-alcoholic fatty liver disease according to morphological studies were identified in 271 cases. Conclusions. 1.In patients with NAFLD, body weight can be equally normal and increased. Among patients with increased body weight, women predominate. 2. In men, there is a moderate positive correlation between the thickness of the subcutaneous fat and the mass of the liver; in women, this connection was not found. 3. Morphologically, coarse fatty degeneration of the liver is more common. 4. Every second patient with NAFLD (49%) died of CVD. Among the dead, men reliably predominate. The dominant cause of death is cardiovascular disease (AMI), followed by impaired cerebral circulation. Mortality peaks in middle and old age. 5. The total mortality from CVD for 3 years according to the pathology department of the Irkutsk Regional Clinical Hospital was 423 cases (19%) (n = 2220). Among all deaths from CVD, one in three (133 cases (31.4%)) had fatty changes in the liver. Conclusion: the results obtained confirm the hypothesis of the existence of a relationship between NAFLD and CVD, which is based on disorders of fat metabolism that develop as a result of impaired normal function of hepatocytes against the background of their fatty lesions. In accordance with this statement, it is necessary to think about considering NAFLD as a component of metabolic syndrome.

Purpose of the study: The aim of the studyis to study the vascular response in response to a test of reactive hyperemia in patients with NAFLD and to identify the relationship of fatty liver damage with endothelial dysfunction. Methods: The study was conducted on the basis of the Irkutsk Regional Order of the Badge of Honor Clinical Hospital, the Angarsk City Clinical Hospital No. 1 and the Consultative and Diagnostic Department No. 1 of the Irkutsk Regional Infectious Diseases Clinical Hospital. Object of study: patients with NAFLD and practically healthy volunteers. All respondents underwent indirect elastometry to diagnose liver fibrosis, and to assess endothelial dysfunction, a sample of reactive hyperemia according to the Celermajer method [15]. Statistical analysis of the data obtained was performed in the program Statistica 13 for Windows. Results: The study was conducted in the period 2014-2016. Examined 64 people aged 25 to 64 years with a confirmed diagnosis of NAFLD and 23 practically healthy volunteers aged 25 to 44 years included in the clinical comparison group. Conclusions: 1. Fibrous changes in the liver were more common among middle-aged people and were more pronounced than among younger people; 2. The correlation of fatty liver damage with endothelial dysfunction was revealed - the greater the degree of fibrosis, the stronger the pathological reaction of the vascular wall; 3. The presence of endothelial dysfunction in steatosis has been proven, and, accordingly, the risk of cardiovascular events. Conclusion: the results obtained indicate the connection of pathological processes: liver damage in NAFLD and the development of CVD.

The aim. To assess the relationships between the degree of severity of coronary and carotid atherosclerosis and the functional liver condition in patients with stable angina pectoris and obesity. Research materials and methods. During the study, two groups of patients were formed. Group I was composed of patients with stable angina and obesity (n = 69), group II - patients with stable angina with a normal body mass index (BMI) (n = 35). Measures of liver function, carbohydrate and lipid metabolism, results of duplex scanning of extracranial brachiocephalic arteries (BCA DS), coronaroangiography (CAG) data were evaluated, and biomarker of hepatic steatosis (НSI) were calculated. The severity of coronary atherosclerosis was analyzed by Gensini score (GS). All patients underwent ultrasound of the liver (ultrasound). Results. In 100% of patients of group I, non-alcoholic hepatic steatosis was detected according to ultrasound. Biomarker of hepatic steatosis (HSI) proved to be more significant among group I patients, while confirming the presence of steatosis. In patients of group I, more significant hypertriglyceridemia was established. Atherosclerotic plaques (according to the BCA DS) were detected in 100% patients of group I and in 68,5% patients of group II. Pronounced stenosis of СCA (≥75% of vessel lumen) is established in 14,5% patients of group I, and is not found among patients of group II. The proportion of patients with significant СA stenosis (> 70% vessel lumen) turned out to be greater in the I group, making up 69,5%, in the II group - 42,8% (χ2=6,9; р=0,009). The GS index values were more significant in patients of group I compared to group II (p = 0.01). Close correlation relationships have been identified between functional liver condition and the severity of coronary and carotid atherosclerosis. Biomarker of steatosis (HSI) have demonstrated their relationship with atherosclerotic lesions of ССA and CA. Conclusion. Against the background of impaired the functional liver condition in patients with stable stenocardia and obesity, more significant expression of coronary and carotid atherosclerosis is determined in comparison with patients with normal body mass index.

Purpose. To assess the risk of readmission and death in patients with alcoholic liver cirrhosis who continue to drink alcohol based on the phosphatidylethanol level. Materials and methods: A study involved 112 patients with alcoholic liver cirrhosis. On the first day of hospitalization, patients underwent a clinical examination, general and biochemical blood analysis, coagulation profile, blood sampling was performed to determine the level of phosphatidylethanol and assessment of the severity of liver cirrhosis on the Child-Pugh scale. A year after the date of hospitalization, a survey was conducted among patients to identify the presence of repeated hospitalizations or a fatal outcome, depending on the results of which patients were divided into groups with favorable and unfavorable course of liver cirrhosis. A ROC analysis of the relationship between the level of phosphatidylethanol and the course of liver cirrhosis was performed. Result: A total of 112 men were included in the study, with an average age of 50.5 years. Of these, 74 patients had a favorable course of liver cirrhosis and 38 unfavorable (36 had readmissions, 18 had a fatal outcome). The average level of phosphatidylethanol was higher in patients with fatal outcome and readmissions compared with patients with a favorable course of liver cirrhosis. In patients who continue to drink alcohol, the risk of readmissions and death during the year increases by almost 5 (p= 0.0005) and 4 (p= 0.04) times, respectively. Conclusion: In patients with alcoholic cirrhosis of the liver, alcohol abuse according to the results of the phosphatidylethanol test is associated with a higher risk of repeated hospitalizations and death within 1 year.

Сhronic autoimmune hepatitis is an urgent problem of modern medicine due to the widespread prevalence among all autoimmune diseases (more than 25%) and the difficulty of its diagnosis due to the lack of reliable serological tests for its detection. The purpose of this work was to study the possibility of the method of monochrome analysis of nanoparticles in noninvasive detection of AIG and to develop an algorithm for rapid diagnosis of chronic autoimmune hepatitis by saliva. The goal was solved by performing a number of tasks: the development of a diagnostic algorithm for monochrome analysis of nanoparticles to determine the severity and pathophysiological orientation of homeostatic shifts in patients with a verified diagnosis of chronic autoimmune hepatitis using samples of oropharyngeal flushes (saliva), as well as the calculation of diagnostic specificity and sensitivity of the test. Materials and methods: The studies were conducted at the Center for European and Oriental Medicine from 2019 to 2022, and 14 patients with a verified diagnosis of autoimmune hepatitis were examined. It was found that the most typical saliva spectra of patients with autoimmune liver damage were characterized by three-modality and predominance of light scattering on particles of super-large diameter (over 1000 nm) and a significant increase in the contribution to light scattering of nanoparticles of small and medium hydrodynamic size, which was statistically significant (p<0.001) when conducting a comparative analysis with the saliva spectra of practically healthy individuals and patients with general somatic liver diseases of non-autoimmune genesis. The indicators of diagnostic sensitivity for autoimmune hepatitis were 95%, diagnostic specificity - 93%. Conclusions: the results of the conducted scientific research were the developed algorithm for the use of laser spectroscopy of saliva for noninvasive rapid diagnosis of chronic autoimmune hepatitis, when with a timely diagnosis, therapeutic measures will be maximally effective and aimed at preventing complications and systemic manifestations of the disease, and the calculation of diagnostic sensitivity and specificity of the method of monochrome analysis of nanoparticles.

Purpose of the research: study of clinical and epidemiological characteristics of Acute Hepatitis B with Delta agent (AHD) in Kyrgyzstan. Materials and Methods: State Reporting Forms No. 1 “Report on infectious and parasitic disease” for 1999-2018 were reviewed. The data of 115 patients with AHD were analyzed, who received inpatient treatment in 2000-2018, Bishkek. The data was processed by Epi Info 3.8.1. Results. In Kyrgyzstan, only AHD 129 cases (0,12 ‰00) were detected for the reviewed period, which was 97,7 times lower than the incidence of Delta free Acute Hepatitis B (AHB). Over the rime, the AHD incidence rate has decreased by 14,6 times with a base rate of decline at the level of 6,8%. The cumulative average AHD incidence in men was 2,4 times higher compared to women (0,17 ‰00 and 0,07 ‰00_, men and women, respectively) and 1,4 times higher compared to the general population level. Analysis of clinical and laboratory data of 115 AHD patients indicated that the disease was associated with medical interventions in 61,7% ± 4,5 patients (71/115). The most frequently reported causes of infection were surgical and dental interventions (50,7% ± 5,9 and 35,2% ± 9,5, respectively). Of the analyzed 109 cases in the age group 16+, 60 patients (55%) had AHD as co-infection, and 49 (45%) - as superinfection. 30% of patients (33/109) had a severe course, which was twice as common in patients with superinfection (43%, 21/49). Conclusion: The low incidence of AHD with the still high prevalence of hepatitis B in the country, the presence of AHD “superinfection” in half of the observed patients with HBsAg-positive status does not reflect the true epidemiological situation and indicates the need to examine all patients with AHV for hepatitis D in order to exclude underdiagnoses. The more severe course of AHD superinfection, compared with co-infection, requires increased prevention and clinical surveillance of patients with chronic HB.

Aim. To estimate the concentration of tumor necrosis factor-alpha (TNF-α), interleukin-6 (interleukin, IL-6), vascular endothelial growth factor (VEGF) in blood serum and to analyze the polymorphism of TNF-α cytokine genes in region 308G / A (rs1800629), IL-6 in region 174G / C (rs1800795) and VEGFA in region 634G / C (rs2010963) in patients with chronic diffuse liver diseases (CDLD) living in the Perm region. Materials and methods. In 193 patients with CDLD and 90 healthy donors, the concentration of cytokines in the blood serum was studied by ELISA and the analysis of cytokine gene polymorphism by PCR was performed. Results. In patients with CDLD, the concentration of pro-inflammatory cytokines TNF-α, IL-6 and the level of VEGF in the blood serum were significantly higher than in the control (p <0.001, respectively), while the maximum level of inflammation markers was noted in liver cirrhosis, and VEGF production - in chronic hepatitis C. Comparative analysis of single nucleotide polymorphisms of cytokine genes showed significant differences in the occurrence of the GA and AA genotypes of the TNF-α gene (G-308A), the carriage of the CG variant of the IL-6 gene (C-174G), as well as the C allele and CC homozygote for marker VEGF (G-634C), which in the population of patients with CDLD in the Perm region were recorded significantly more often than in the cohort of donors, which allows us to consider them as genetic markers of the risk of developing CDLD. Conclusion. An increase in the concentration of pathogenetically significant cytokines TNF-α, IL-6 and VEGF in liver diseases can develop against the background of gene polymorphisms of these molecules. Genetic markers can be used to assess the risk of developing and progression of CDLD.

Relevance: Controversial issues of enzyme replacement therapy for cystic fibrosis continue to be studied, without losing relevance against the background of taking targeted drugs. Studies show that there is a large scale in the dosage of pancreatin that goes beyond the recommended values and there is no unified approach to prescribing the drug related to national and individual characteristics. Currently, there is insufficient data to substantiate consensus recommendations on enzyme therapy from the standpoint of evidence-based medicine. There is a need for scientific substantiation of the accepted therapeutic algorithm, search for optimal doses, calculation methods, correction, development of an individual approach to the appointment of pancreatin in cystic fibrosis. Objective: to study the features of pancreatin dosing in children with pancreatic insufficiency of cystic fibrosis in the Russian Federation Material and methods. 140 children (boys - 73, girls - 67) with CF aged from 1 year to 18 years (average age 8,9±5,8 years) were examined in the Department of cystic Fibrosis Scientific and Clinical Institute of Childhood of the Ministry of Health of the City of Mytishchi (clinical base of the scientific and clinical Department of cystic fibrosis). The study was conducted in 2018. The nutritional status (anthropometric indicators) of the pancreatin dose per day and for each meal was assessed using 2 calculation methods: units/kg of body weight and units/g of fat in food. Separately, these indicators were analyzed in a group of patients homozygous for the genetic variant F508del of the CFTR gene Design: cross-sectional study Results. The study showed that 67% of patients in the general group and 68% in the subgroup of patients homozygous for the genetic variant F508del of the CFTR gene received doses of pancreatin in reference values (up to 10,000 EU/kg of body weight per day). When calculating the pancreatin dose by the method per gram of fat in food, most of the patients (59%) in the general group and 47% of patients in the F508del homozygous subgroup received pancreatin doses of less than 2000 EU/g of fat, which is less than the reference values (2000-4000 EU/g). The results are consistent with the data of recent studies indicating an acceptable dosage range of pancreatin 1000-4000 EU/g of fat in food. The median daily dose of pancreatin of the subgroup with the genetic variant F508del of the CFTR gene was 1700 EU/g of fat in food, and in the general group 1500 EU/g of fat (p≥0.05), which can be attributed to the peculiarities of dosing and the need for pancreatin in the Russian pediatric population of patients with cystic fibrosis. The BMI percentile did not differ in subgroups with different doses of pancreatin when calculated by two calculation methods. The median daily dose of pancreatin in patients homozygous for the genetic variant F508del of the CFTR gene and the general group did not differ statistically. Conclusion. Most of the children in the general group and in the subgroup of homozygous F508del genetic variant received pancreatin in the range of 6000-10000 EU/kg of body weight. Most patients in the general group received less than 2000 EU/g of fat, unlike the subgroup with the F508del/F508del mutation - 2000-4000 EU/g of fat (p≥0.05). The median pancreatin of the subgroup with the F508del/F508del mutation was 1700 EU/g of fat in food, in the total group 1500 EU/g of fat (p≥0.05). High doses of pancreatin are not associated with nutritional status (BMI percentile).

Objective: to improve diagnostic and therapeutic tactics in patients with cholelithiasis in combination with NAFLD, taking into account the impact of comorbidity. Materials and methods: We examined 180 people who applied to the Lotos Medical Center in Chelyabinsk in the period 2018-2020 with cholelithiasis and NAFLD at the age of 19 to 65 years. The study included 128 women (72%) and 52 men (28%). The mean age of the participants was 51.3±9 years. The work took into account anamnestic (comorbid pathology) anthropometric data (height, body weight, body mass index, waist circumference). All patients underwent general clinical, biochemical blood tests, ultrasound of the abdominal cavity, MSCT of the abdominal cavity with an assessment of the density of liver tissue, bile and gallbladder stones. Results of the study: The study showed that among patients with cholelithiasis in combination with NAFLD, 56% had comorbidity. Gallstones of low density were found in 41.6%, high density in 58.4%. Comorbid pathology was represented by obesity, cardiovascular diseases, pathology of the endocrine system, diseases of the gastrointestinal tract and diseases of the kidneys and urinary system. In the group of patients with gallstones with a density of more than 75 Hounsfield units, comorbid pathology was more common, and the degree of liver steatosis and fibrosis was higher. During treatment with UDCA 15 mg/kg, positive dynamics was observed in patients with low-density stones: a decrease in stone density and size (effective litholysis), normalization of liver density, normalization of cytolysis, cholestasis, and carbohydrate metabolism. In patients with gallstones over 75 Hounsfield units, there was a decrease in bile density without effective litholysis, normalization of cytolysis stigmas, cholestasis, correction of lipid and carbohydrate metabolism. Conclusion: in patients with cholelithiasis in combination with NAFLD, comorbid pathology is more common, which negatively affects the effectiveness of litholysis and worsens the prognosis in these patients. Medical litholysis in these patients is possible only at the initial stage of the disease in the presence of stones of low density and size. UDCA therapy makes it possible to control the density of bile and the size of gallbladder stones, the activity of the inflammatory process in the liver, preventing the progression and complications of NAFLD and cholelithiasis in comorbid patients.

Currently, peptic ulcer disease remains the most common disease of the digestive system. Ulcerative bleeding is a terrible complication. The main condition for the successful conservative treatment of gastrointestinal bleeding that occurs against the background of acid-dependent diseases is adequate acid-reducing therapy. We conducted a study comparing the different modes of administration of proton pump blockers. To this end, three groups of the study were formed: the first group: the drug Rabeprazole was obtained as an antisecretory therapy. The dosing regimen consisted in the introduction of a bolus of 80 mg, then a constant infusion of the drug at a rate of 8 mg per hour for the first 72 hours, after which the transfer to the oral form of 20 mg ×2 times a day; the second group: received the drug rabeprazole intravenously in a dosage of 40 mg 2 times a day; the third group: received the drug rabeprazole intravenously in a dosage of 20 mg 2 times a day for the first 72 hours, then transfer to the oral form of 20 mg ×twice a day. The use of PPIs in various dosages in the study groups significantly reduced the risk of bleeding relapses and deaths. We have shown that the use of PPIs in reduced dosages is also an effective method of treating patients with ulcerative gastroduodenal bleeding.

. Identify cytolysis syndrome among patients with COVID-19 and explore the potential relationship between the course of COVID-19 and liver damage. Materials and methods. 450 people with a diagnosis of "U07.1 - Coronavirus infection COVID-19, virus identified" were examined, undergoing and inpatient and outpatient treatment at Tuymazinskaya Central District Hospital. CT scan of the chest organs, biochemical blood test with calculation of ALT, AST, total protein, glucose, total bilirubin, APTT, PTI, INR, fibrinogen were evaluated. Results. The presence of cytolytic syndrome was detected in 217 (48.2%) patients. The ALT level was 60 [23;72] U/L, and the AST level was 45 [22;57] U/L. Between the severity of the course and the ALT level, a direct, strong significant correlation was revealed (ρ=0.724, t=22.26, p>95%). A direct, significant correlation of moderate strength was found between the severity and percentage of lung parenchymal lesions (ρ=0.68, t=19.62, p>95%), AST level (ρ=0.68, t=19.53, p>95%), age of patients (ρ=0.51, t=12.55, p>95%), BMI (ρ=0.4, t=9.44, p>95%). Comparing the degree of damage to the lung parenchyma with the level of AST, a direct, significant correlation of moderate strength (ρ=0.5, t=12.38, p>95%) was revealed, as well as with the level of ALT (ρ=0,5, t=11.98, p>95%), total protein level (ρ=0.38, t=8.8, p>95%), age (ρ=0.35, t=7.85, p>95%. Conclusion. Clinical manifestations of COVID-19 are characterized by polysyndromicity, including a cytolytic syndrome. Changes in liver function parameters found in COVID-19 are associated with the severity of the infection, age and BMI. An important point in the post-COVID rehabilitation of patients is inclusion of hepatoprotectors.

Aim: To evaluate features of changes of liver function tests (LFTs) in COVID-19. Methods: We included 50 patients with confirmed COVID-19 and abnormal LFTs. The average age was 55 [46; 66]. 45 patients (90%) were with COVID-19 associated pneumonia. Lung damage involvement according to lungs computed tomography ranged from 5% to 70%. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), quik’s prothrombin and total protein were analyzed. Results: The debut of liver cytolysis was on average 8 [7; 11] sick days of COVID-19. ALT levels elevated on average 2,28 [1,41; 3,27] times. An increase in AST correlated with changes in ALT (r=0,86; p<0,05), it was 2,08 [1,44; 3] times. De Ritis ratio was 0,73 [0,49; 1,15]. Only 2 patients (4%) had hyperbilirubinemia. 60% patients had an increase in GGT - 1,92 [0,79; 3,05] times. 1,79 times ALP was in one patient only. Many patients had not signs of hepatocellular insufficiency - only 5 patients (10%) had decrease in Quik’s prothrombin; hypoproteinemia was observed in 7 patients (14%). The changes in LFTs were reversible, normalization of ALT was achieved in 67%, AST - in 76% of patients within a month. The levels of ALT (r=0,52; p<0,05) and AST (r=0,48; p<0,05) correlated with ferritin. Conclusions: Abnormal LFTs in COVID-19 were characterized by increase in ALT, AST, GGT and decreased de Ritis ratio. Total bilirubin, ALP, Quik’s prothrombin were normal in most patients. The identified changes in the majority of cases returned to normal within the month.

Purpose of the work: to study liver elasticity indicators, hydrogen and methane levels in exhaled air, and their associations with clinical and biochemical parameters for patients who underwent COVID-19. Materials and methods. We examined 30 patients (mean age 51.8±2.91) who underwent COVID-19 (confirmed by SARS-CoV-2 RNA test or SARS-CoV-2 antigen) 12-16 weeks after the onset of the first symptoms, of which 11 were diagnosed with pneumonia. 19 people (mean age 47.1±3.09) who did not have COVID-19 made up the comparison group. The patients underwent a clinical and biochemical study, the degree of liver fibrosis was determined (FibroScan® 502 Echosens, France), the levels of hydrogen (H2) and methane (CH4) in the exhaled air were measured (baseline and after taking lactulose solution) (GastroCheck Gastrolyzer, Bedfont Scientific Ltd., England). Results. Past COVID-19 infection was directly correlated with age (r=0.331, p=0.022), male gender (r=0.324, p=0.025), and presence of liver fibrosis (r=0.291, p=0.044). COVID-19 survivors were more likely to have liver fibrosis (p<0.001) and higher liver elasticity in kPa (p=0.018) with overweight and obesity (63.3%) and elevated body mass index (p= 0.03) compared with the control group. The presence of liver fibrosis was associated with moderate pneumonia (p<0.001). Among those who had COVID-19, there were significantly more non-producers of methane (p=0.02), fewer people with an average level of methane in exhaled air (p=0.016). In COVID-19 convalescents, bacterial overgrowth syndrome (BOS) was detected less frequently than in controls (p=0.04), but signs of delayed intestinal transit were more often recorded (p<0.05). The presence of liver fibrosis in survivors of COVID-19 is associated with BOS detection (23.3% vs. 5.2%, p<0.001), which probably contributes to the pathogenesis of liver damage. Hydrogen levels at 120 min and methane at 60 min after ingestion of lactulose solution distinguished between COVID-19 convalescents and COVID-19 survivors with an AUC of 0.683 and 0.660, respectively. The associations of the levels of gases in the exhaled air with clinical and biochemical parameters were revealed: the presence of overweight and obesity showed inverse associations with the level of methane production (r= -0.342, p<0.05), its concentration after taking lactulose at various time intervals, and also the basic level of hydrogen (r= -0.313, p<0.05); the degree of obesity was also inversely correlated with the level of methane emission (r= -0.368, p=0.038). Direct links were established between indicators of liver elasticity in kPa and the level of hydrogen production (r=0.275, p<0.05). Conclusions. Obtained indirect signs of pronounced changes in the intestinal microbiome, which obviously contribute to a more severe course of COVID-19, the development of liver fibrosis, so the impact on the intestinal microflora can be considered as a potential target in the treatment of patients with COVID-19.

The purpose of the study is to summarize the first experience of liver transplants. Material and methods. Liver transplantation was performed at the Regional Clinical Hospital. 5 liver transplants from a posthumous donor were performed. Based on the available data, the analysis was carried out according to the following criteria: gender, age, MELD- Na index, cause of liver cirrhosis, method of liver transplantation, duration of surgery, postoperative complications, average bed-day, outcome. Results. In total, 5 liver transplants were performed from a posthumous donor. Among the patients there was 1 man and 4 women. The age of men is 41 years, women are 55.4 ± 9.2 years on average. The MELD- Na index is from 15 to 28, on average 17.8 ± 5.1. When transplanting a cadaveric liver, the method of classical orthotopic liver transplantation was used in 4 cases, in one the piggyback technique was used. The duration of surgical intervention in minutes averaged 394 ± 17.4. Postoperative complications on the Clavien-Dindo scale ranged from I to IIIb. The average bed-day of the patient’s stay in the hospital is 20.2 ± 8.9, including 6.2 ± 1.7 days in the intensive care unit. In all 5 cases, the outcome of liver transplantation is satisfactory. Conclusion. The first results of liver transplantation on the basis of the Regional Clinical Hospital showed that performing such a level of operations is possible in a multidisciplinary medical institution.

The aim. To study the hepatoprotective effect of the aqueous extract of the leaves of Gynura Procumbens (GP) on an experimental model of fructose-induced non-alcoholic liver steatosis in laboratory animals. Materials and methods. The experimental study was conducted for 30 days on 25 non-inbred sexually mature white male rats aged 8-9 months, weighing 400-530 g., which comprised 3 groups: “Control” (received a full-fledged balanced standard granular feed), “fructose-induced steatosis” (feeding was carried out similarly to animals of the first group using a 15% solution of fructose as drinking water) and “Steatosis + GP” (simulated liver steatosis and simultaneously daily intragastric daily administration of GP leaf extract was performed. Laboratory parameters (transaminases, glucose and lipid spectrum) in blood serum, biometric indicators (animal mass, liver mass and mass coefficient) and histological examination of the liver were studied in all animals according to the conclusion from the experiment. Results. The course of fructose-induced liver steatosis in experimental animals is accompanied by lipid spectrum disorders, hepatomegaly without the formation of general obesity and morphological changes in liver tissue in the form of fatty degeneration without signs of inflammation and fibrosis. Conclusion: The course intragastric administration of an aqueous extract of GP leaves to experimental animals with steatosis does not significantly affect the lipid spectrum, but prevents the formation of hepatomegaly and morphological changes characteristic of steatosis in liver tissue.

Metabolic syndrome (MS) is a widespread polyethiological clustering characterized by metabolic, hormonal disorders and clinical manifestations that significantly increase the risk of developing cardiovascular diseases, atherosclerosis, type II diabetes and other pathological conditions. An important role in the development of MS is assigned to the intestinal microbiota. To develop new therapeutic agents for correction of MS manifestations, it is necessary to develop adequate experimental models. In this paper, comparative studies were conducted to assess the parameters of lipid metabolism, the content of peptide hormones, morphological changes in liver tissue, and the quantitative and generic composition of the intestinal microbiota of mice. Experimental models of experimental hyperlipidemia (HL) caused by the introduction of poloxamer 407 (Pol407) and alimentary MS (a diet with fructose and the addition of cholesterol to the feed) were used. Significant increase in the levels of cholesterol, triglycerides, and low-density lipoprotein (LDL) was found in the group of mice treated with Pol407 injections. To assess the indicators of carbohydrate metabolism in blood serum, the following markers were determined: insulin, adiponectin, leptin. In the alimentary MS model a decrease in adiponectin in the blood serum, while insulin level was increased. In both experimental models, significant changes in the gut microbiota of mice were observed. They were associated with the manifestation of metabolic dysbiosis - an increase in the representation of Firmicutes (staphylococci, streptococci, enterococci) in the biomaterial, changes among representatives of both facultative (E. coli), and transient (Enterobacter bacteria) microflora. In addition, dystrophic, as well as morphological changes and signs of inflammation in the liver tissue were noted in both groups.

Objectives: The aim of this study was to evaluate the hepatoprotective activity of resveratrol in patients with morphofunctional liver disorders due to mechanical jaundice. Methods: The controlled mechanical jaundice was simulated on the rats under anesthesia by drainage of the choledochus and its plugging. In the control group decompression of the choledochus was performed on the 3rd day and intravenous infusion of 0,9% sodium chloride solution was administrated for 12 days. In the experimental group after billiar decompression, resveratrol was administered intravenously at a dose of 20 mg/kg. The following were studied: level of malondialdehyde, catalase, bilirubin, alanine aminotransferase (ALAT), aspartate aminotransferase; liver histology was performed. Results: Catalase was 3.9 times reliably increased, and the activity of malonic dialdehyde and ALAT was 2.0 and 3.6 times reliably decreased in experimental group compared to the control group. Microscopic shows edema and destruction of the liver were reduced, the architectonic of the liver lobules was recovered. Conclusion: Application of resveratrol in mechanical jaundice decreased the processes of free-radical oxidation and level of the liver cells cytolysis markers which morphologically was shown by edema reduction, restoration of the liver lobules structure.

Nonalcoholic fatty liver disease (NAFLD) is the most common reason of chronic liver disease. NAFLD causes a wide array of liver conditions ranging from simple steatosis - to nonalcoholic steatohepatitis (NASH) and advanced hepatic fibrosis. Numerous studies show that epigenetic processes are also involved in the pathogenesis of NAFLD. Shifts in the regularity of genomic DNA methylation can cause aberrant gene expression in NAFLD. Pathogenesis of NAFLD is not entirely understood, but it is well-known that obesity, diabetes and metabolic abnormalities played a significant role in the disease development and progression. Epigenetics is known as an inheritable phenomenon which influences the expression of gene without altering the DNA sequence, offers a new view on the pathogenesis of NAFLD. Moreover, epigenetic mechanisms including DNA methylation, posttranslational histone modifications and non-coding RNAs seem to orchestrate various aspects of NAFLD. Histone acetylation affects gene expression profiles in NAFLD. Abnormal histone changes induce insulin resistance, progression of type 2 diabetes mellitus, and subsequent development of NAFLD. This review reflects new advances in the study of epigenetic mechanisms for the development of NAFLD and the formation of innovative therapeutic targets and the long-awaited diagnostic and prognostic tools based on them.

Diabetes mellitus is a widespread disease in the world, despite advances in understanding the molecular mechanisms of the development of multifactorial processes associated with this nosology. The review material is devoted to modern ideas about the immunogenetic causes of diabetes, changes in metabolism in the violation of carbohydrate metabolism, types of the disease and the principles of laboratory diagnostics in accordance with modern WHO criteria. Information on the molecular causes of functional insulin deficiency is presented. The biochemical aspects of hyperglycemia as the main mechanism of organ and tissue damage resulting from protein glycosylation are considered. The article describes the metabolic pathways of disorders of carbohydrate, lipid, protein, water-salt metabolism, leading to the occurrence of glucosuria, polyuria, polydipsia, ketonuria, ketoacidosis and other complications of diabetes mellitus. Knowledge of the modern concept of the development of various forms of diabetes mellitus from the point of view of biochemistry of pathogenesis, molecular medicine will be useful for doctors of all specialties and in clinical laboratory diagnostics.

Over the past 10 years, an in-depth study of metabolic processes in chronic liver diseases and the rapid development of new technologies in the production of macro- and nutrients, pharmacological nutrients in clinical dietetics and nutritional science have led to the creation of fundamentally new approaches in nutritional therapy for these diseases. It is recognized that dietary interventions for chronic liver diseases should not only follow the general recommendations indicated as the need for energy and protein, but also contribute to the normalization of the amino acid composition of the blood, the metabolism of macro- and microelements, vitamins, etc. Methods of dietary correction are of particular importance hepatic encephalopathy, as well as the use of micro- and pharmacological nutrients for therapeutic purposes.

The concept of this literature review is based on the scientific hypothesis that inflammation, which is the basis of various diseases, has common features, stages, pathophysiologically active substances that control the activity of inflammatory reactions, and general genetic control. In this literature review, individual diseases are grouped into several models based on the leading pathogenetic mechanisms of inflammation: autoimmune, microbial, lymphoproliferative, metabolic, and allergic. In connection with the importance of 25(OH) D for human health, its role in the pathogenesis of a number of diseases, the diversity of functions and the complexity of metabolism due to polymorphism of regulatory genes, on the one hand, it seems very important to monitor the supply of this biologically active effector to various population groups, as well as, timely detection of insufficient supply and the need for additional intake of vitamin D, switching to targeted therapy if necessary, and on the other hand, the study of certain features of the molecular genetic mechanisms of its influence on the course and outcome of diseases with various pathophysiological mechanisms of inflammation.

The incidence of gallstone disease (GSD) and metabolic syndrome (MS) is increasing every year. The ICD-10 does not have the diagnosis of “metabolic syndrome” and it has been coded on the basis of the diseases despite its wide prevalence now. These are multifactorial diseases, the pathogenesis of which is intertwined and mutually aggravate their courses. There are both external and internal reasons of forming the stones in the biliary tract. Genetic factors play a significant role in the internal causes of cholelithiasis. The genetic characteristics of the patient allow to work out a personalized approach. It increases the success of drug therapy. MS is one of the main predisposing factors for the development of cholelithiasis. It also leads to more severe course of the latter. The pathogenetic mechanisms of the patologies developments are considered in the article presented with the special attention paid to the genetic component of cholelithiasis.

Alcohol abuse is a socially significant problem that makes a significant negative contribution to the world health statistics. Alcohol is one of the main factors of mortality in Russia. Despite the current situation, the existing diagnostic approaches to patients with possible alcohol abuse and alcohol-associated diseases do not always allow us to determine the direct contribution of alcohol to the severity and prognosis of the course of these diseases. Objective diagnostic tools for identifying and monitoring the fact of alcohol consumption and its pattern in clinical practice can be useful from the point of view of managing the patient’s disease. In addition, informing the patients about the possibilities of such a diagnosis can motivate them to refuse to take alcohol during further treatment, thereby improving the prognosis of the disease. Currently, various approaches have been developed to assess the fact and nature of alcohol consumption, including the direct determination of ethanol in the blood, but not all of them have found their wide application in clinical practice. In this review, we presented information about the main alcohol biomarkers currently developed: alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltranspeptidase, mean corpuscular volume, carbohydrate-deficient transferrin, ethylglucuronide and ethylsulfate, phosphatidylethanol, ethyl esters of fatty acids, described their disadvantages and advantages in terms of application in clinical practice. Despite the high sensitivity and specificity of some alcohol biomarkers, for example, phosphatidylethanol, the results of laboratory assessment of the content of alcohol biomarkers should be interpreted only in the context of all relevant factors, including the clinical presentation, medical history, mental and physical health of the patient

The growth of liver tests in the second half of pregnancy is most often caused by two reasons - Intrahepatic Cholestasis of pregnancy (ICP) and rarely diagnosed Drug-Induced Liver Injuries (DILI). In Assisted Reproductive Technology (ART)-induced pregnancies that are accompanied by powerful drug support, the incidence of drug-induced cholestasis increases. This is due to the combined use of gestagens and other drugs that have hepatotoxic potential for the prevention of miscarriage. The article reveals the risks of IVF, which is often performed for women in late reproductive age, accompanied by multiple pregnancies, somatic pathology, thrombophilia and forced polypharmacy. The article presents an analysis of the clinical observation of a pregnant woman as a result of IVF, who developed acute drug hepatitis against the background of polypharmacy, and its examination according to the criteria of the European Association for the Study of the Liver (EASL) and the RUCAM algorithm. The author believes that the limitation of the RUCAM scale is manifested by insufficient consideration of the effect of pregnancy and polypharmacy on the development of DILI. According to the author, it is necessary to differentiate the DILI from ICP in connection with the peculiarities in the management tactics, despite their probable genetic affinity and clinical and laboratory similarities. The author suggests that DILI during pregnancy is a reservoir for the subsequent development of chronic diffuse liver diseases in women. In this regard, such patients need the observation of a therapist for 6-12 months after childbirth.

Wilson’s disease (hepatocerebral dystrophy) is a rare hereditary disease that is caused by impaired copper metabolism affecting many organs, but mainly the liver and nervous system. Interest in the problem does not subside, because diagnosis and management of patients presents certain difficulties. The article highlights the literature data, clinical recommendations when discussing their own clinical observation of two patients (brother and sister) in whom the disease was diagnosed in childhood. Presented are clinical data, dynamics of laboratory parameters during 15 years of follow-up against the background of adequate chelation therapy with D-penicylamine and zinc sulfate, as well as during interruption of treatment. The necessity of adherence to a lifelong regimen of therapy is emphasized, since it is this tactic that demonstrates effectiveness in improving the prognosis of the disease.