Aim: to familiarize gastroenterologists, therapists, functional diagnostics and general practitioners (family doctors), radiologists, and endoscopists with modern methods of diagnosis and treatment of achalasia of the cardia.Key points. Achalasia is an idiopathic neuromuscular disease manifested by a functional disorder of the patency of the cardia due to a lack of coordination between swallowing, reflex opening of the lower esophageal sphincter, and the motor and tonic activity of the smooth muscles of the esophagus. The etiology of achalasia remains unclear. However, it is believed that the key role belongs to the changes in the myenteric (Auerbach’s) intermuscular plexus of the enteric nervous system of the esophagus, leading to loss of neuronal function. The following hypotheses have been proposed as the main mechanisms for the development of achalasia: genetic predisposition, exposure to viral infections, and idiopathic autoimmune triggers. Patients with suspected achalasia require a comprehensive instrumental examination, including esophagogastroduodenoscopy, timed barium esophagogram, and esophageal manometry. In recent years, high-resolution esophageal manometry has been recognized as the gold standard for achalasia diagnostics. To analyse the obtained data, the Chicago classification is recommended — it allows to ascertain the type of achalasia, which determines the choice of treatment method and the assessment of the prognosis of the therapy effectiveness. Treatment of achalasia can be pharmacological, endoscopic (pneumatic balloon dilation, peroral endoscopic myotomy, botulinum toxin injection), aimed at regulating the tone and motility of the esophagus and cardia while preserving all anatomical structures, and surgical (laparoscopic esophagocardiomyotomy, esophagectomy), in which the muscle fibers of the esophagus and esophagogastric junction are intersected or the altered esophagus is completely removed with simultaneous formation of an artificial esophagus from the stomach or colon (esophagoplasty).Conclusion. Implementation of the developed clinical guidelines can help to establish a diagnosis in a timely manner, which will lead to an improvement in the quality of medical care for patients with achalasia.

Aim: to review the pathogenesis of thrombocytopenia and possible ways of its correction in patients with liver cirrhosis before elective surgical interventions or invasive procedures to optimize clinical practice.Key points. Thrombocytopenia is a common hematological complication of liver cirrhosis, affecting up to 75–86 % of patients with decompensated cirrhosis. Thrombocytopenia is associated with increased risks of bleeding and mortality. It complicates the management of patients, especially those who require invasive procedures, many of which carry a risk of bleeding. This risk of bleeding varies with the severity of thrombocytopenia, coagulation status, and type of invasive procedure.Moderate-to-severe thrombocytopenia can interfere with life-saving interventions, such as invasive procedures/surgeries. Delayed care is associated with longer hospital stays and greater medical costs. Thrombopoietin receptor agonists (avatrombopag) should be considered for the management of cirrhotic patients with severe thrombocytopenia undergoing elective invasive interventions with a high risk of bleeding.Conclusion. Thrombopoietin receptor agonists (avatrombopag) have demonstrated high efficacy and safety and are considered a promising first-line option for the management of severe thrombocytopenia in patients with liver cirrhosis undergoing elective surgical interventions or invasive procedures.

Aim: to demonstrate difficulties of differential diagnostics in the case of combined autoimmune pancreatitis, sclerosing cholangitis and ulcerative colitis. Colonic lesions that initially had low grade of inflammation were resistant to immunosuppressive therapy.Key points. A 28-year-old female patient was admitted to the clinic for jaundice associated with pruritis. Based on the characteristic beaded appearance of the intrahepatic bile ducts at magnetic resonance cholangiopancreatography, primary sclerosing cholangitis (PSC) was diagnosed. Subsequent examination revealed focal pancreatitis and total colitis with histological pattern, consistent with ulcerative colitis (UC). To determine the etiology of pancreatitis IgG4 serum level was examined, that showed over 2-fold elevation. This required differential diagnostics between PSC with IgG4 elevation, UC and type 2 autoimmune pancreatitis (AIP) (more common in European population) on one hand and IgG4-associated systemic disease (more common in Asian population) with bile ducts, pancreas and large intestine involvement on the other. Liver histology failed to reveal histological signs characteristic of any type of cholangitis, pancreatic biopsy was not performed. Immunosuppressive therapy (steroids followed by thiopurines) resulted in rapid improvement of the pancreatic changes while no response was achieved for bile ducts and the colon that was in favor of the first concept (PSC + type 2 AIP + UC). The patient was recommended to receive biologic therapy for UC remission induction.Conclusion. Differential diagnostics of combined autoimmune lesions of the liver, the pancreas and colon may be complicated and carried out ex juvantibus according to response to immunosuppressive therapy.

The prevalence of gastroesophageal reflux disease is steadily rising. The number of patients with non-erosive reflux disease is increasing worldwide, including the form of the disease refractory to standard therapy. This article presents current data on the pathogenesis, diagnosis, and therapeutic approaches for patients with refractory non-erosive reflux disease. Key words: proton pump inhibitors, non-erosive reflux disease, refractory symptoms

Introduction. Genetic predisposition in combination with environmental factors and the patient’s psychological and emotional state play a key role in the development of irritable bowel syndrome (IBS). Studies of association between genetic polymorphisms and IBS can help in understanding the key pathophysiological mechanisms. To date, 11 meta-analyses on this issue have been published, however, none of them comprehensively summarize the data on the prevalence of genetic polymorphisms in IBS with predominant constipation (IBS-C).Aim: to summarize the published data on the impact of genetic polymorphisms on the risk of IBS-C.Materials and methods. A literature search was performed in the PubMed and Scopus databases. Identified studies were used for a meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Publications investigating genetic polymorphisms in patients with IBS-C were included in this analysis.Results. A total of 34 studies met the inclusion criteria. The collected data were sufficient to conduct a meta-analysis on polymorphisms of three of the listed genes: SLC6A4 (10 articles), GNB3 (5 articles), ADRA2A (4 articles). No significant association was found between the SLC6A4 (5-HTTLPR) polymorphism, GNB3 c.825C > T (rs5443) polymorphism and either IBS or IBS-C. It was found that ADRA2A 1291C>G polymorphism was significantly associated with both IBS and IBS-C.Conclusions. Our meta-analysis revealed that ADRA2A 1291C>G polymorphism was significantly associated with both IBS and IBS-C in the mixed population. Neither homozygous nor heterozygous variants of the SLC6A4 (5-HTTLPR) polymorphism and GNB3 C825T polymorphism were associated with either IBS-C or IBS as a whole.

Introduction. As a result of portal hypertension (sequestration of platelets in an enlarged spleen) and liver failure (decreased production of thrombopoietin in the liver) in liver cirrhosis, thrombocytopenia develops, which is associated with the risk of periprocedural/perioperative bleeding complications. There are still unresolved questions regarding risk stratification of bleeding complications, the prognostic role of thrombocytopenia, as well as the need for treatment of thrombocytopenia and its methods.Materials and methods. The Russian Scientific Liver Society selected a panel of experts in the field of therapeutic and surgical hepatology, hematology, transfusion medicine to make reasoned statements and recommendations on the issue of treatment of thrombocytopenia before elective surgery / invasive procedures in patients with liver cirrhosis.Results. Relevant clinical issues were determined based on the PICO principle (patient or population, intervention, comparison, outcome). The Delphi panel made five questions and gave reasoned answers, framed as ‘clinical practice recommendations and statements’ with evidence-based comments. The questions and statements were based on the results of search and critical analysis of medical literature using keywords in English- and Russian-language databases. The formulated questions could be combined into four categories: bleeding risk stratification, the prognostic value of thrombocytopenia, the necessity and methods of thrombocytopenia drug correction, and bleeding risk reduction.Conclusions. The results of experts' work are directly related to high-quality management of patients with liver cirrhosis and thrombocytopenia, who have scheduled invasive procedures/surgery. Thus, this recommendations and statements can be used in clinical practice.

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Aim of investigation. To demonstrate unusual clinical symptoms and difficulties of diagnostics of disseminated tuberculous process.Material and methods. The 25 year-old patient, who was managed for 10 years for liver cirrhosis of nonspecified etiology, was investigated. The careful analysis of clinical presentation of disease, data of physical examination, results of radiological and other methods of diagnostics was carried out.Results. It was possible to suspect and subsequently to confirm disseminated tuberculosis with involvement of the lungs, the heart, pericardium, pleura, mesenteric lymph nodes, the liver; chronic right-sided tubercular pleurisy with pleurocirrhosis; constrictive pericarditis with signs of right ventricular failure; cardiac liver fibrosis (Pick's pseudocirrhosis); mixed portal hypertension.Conclusion. The detailed analysis of clinical presentation of disease, physical data and application of complex of visual and other methods of investigation expand potential of diagnostics of disseminated tuberculous process.

Aim: to discuss current views on the clinical significance, diagnostic opportunities, and therapeutic approaches in the treatment of small intestinal bacterial overgrowth (SIBO) as an important component in the gut microbiota function assessment, to assess the awareness of physicians and the opportunities in the diagnosis and treatment of this disease in patients in the Federal districts of the Russian Federation, as well as to present the proceedings of the Expert Council held on December 16, 2023 in Moscow.Key points. SIBO is a common syndrome often associated with irritable bowel syndrome, liver cirrhosis, asthma, and congestive heart failure, being also a predictor of early death in the elderly. Today, in many regions of the Russian Federation, there are limitations for instrumental diagnosis of this disease — lack of awareness among doctors, unavailability of gas analyzers for diagnosing SIBO, lack of information about the need to diagnose SIBO in the standards of compulsory health insurance. Rifaximin is the first-line treatment due to the highest therapeutic efficacy. One of the ways to increase the efficacy of SIBO treatment is to include strain-specific probiotics in the treatment regimen. Saccharomyces boulardii CNCM I-745 is thought to be the most studied, promising probiotic. The review also presents statistical data on the issues in the diagnosis and treatment of SIBO in the regions of the Russian Federation.Conclusion. Optimization of approaches to the diagnosis and treatment of SIBO, the development of domestic gas analyzers, increasing the awareness of physicians in all regions of the Russian Federation, as well as the development and optimization of clinical recommendations appear to be necessary measures to increase the effectiveness of medical care, the duration and quality of life of the Russian population. These goals can be achieved within the framework of Federal programs under the supervision of specialized reference centers of the Ministry of Health of the Russian Federation.

Aim: to provide data on the pathogenesis of functional biliary pain and provide rationale for the use of trimebutine for this indication.Key points. Biliary pain is one of the most frequent reasons for patients to see a doctor. The diagnosis of functional disorder of the gallbladder and Oddi's sphincter is legitimate only after the exclusion of organic causes from both the gastrointestinal tract and other organs and systems. The initial appeal to surgeons with a complaint of pain in the epigastrium or right hypochondrium may lead to unjustified surgical intervention that does not bring relief to the patient's suffering. The consequences of cholecystectomy also have an anatomical and physiological justification for the occurrence or preservation of biliary pain. Currently, two main hypotheses are being considered to explain its cause: increased intraluminal pressure due to morphological and functional obstacles to bile outflow and visceral hypersensitivity. In the multilevel system of regulation of the gallbladder and sphincter apparatus, the opioid system occupies a special place. The agonist of peripheral receptors of the enkephalinergic system, trimebutine, in clinical studies led to the relief of biliary pain in more than 80 % of patients with functional biliary disorders, while a significant decrease in the severity of diarrhea, dyspeptic, and constipation syndromes was revealed.Conclusion. The prescription of the peripheral receptor agonist of the enkephalinergic system, trimebutine, is pathogenetically justified for functional biliary pain.

Aim. These recommendations are developed for practitioners in order to familiarize them with modern diagnostic methods, management features and pharmacotherapy of patients with gastroesophageal reflux disease (GERD).General provisions. GERD is the most common reason for patients to visit clinics. There are esophageal and extraesophageal manifestations of GERD. Patients' complaints of heartburn and regurgitation remain the most sensitive and specific clinical manifestations of GERD. The diagnosis of GERD is established on the basis of anamnestic data, instrumental examination (detection of reflux esophagitis during upper gastrointestinal endoscopy, detection of pathological gastroesophageal reflux with 24-hour pH-metry or/and 24-hour pH-impedance monitoring). Patients with suspected GERD and the absence of erosive and ulcerative changes in the mucous membrane of the esophagus or the presence of erosive esophagitis of Grade A according to Los Angeles Classification of Gastroesophageal Reflux Disease are recommended to conduct 24-hour pH-metry on PPI off to exclude or confirm the diagnosis of GERD. Patients with extraesophageal manifestations of GERD without classic symptoms (heartburn, regurgitation) are recommended to undergo 24-hour pH-impedance monitoring with discontinuation of proton pump inhibitor therapy. When deciding on surgical treatment, all patients need to perform high-resolution esophageal manometry and 24-hour pH-impedance monitoring. Complications of GERD include bleeding, strictures, Barrett’s esophagus and esophageal adenocarcinoma. The main groups of medications used in the treatment of GERD are proton pump inhibitors (PPIs), potassium-competitive acid blockers (P-CABs), alginates, antacids, and prokinetics. PPIs are the drugs of choice in the treatment of both symptoms of gastroesophageal reflux disease and existing erosive esophagitis. Combination therapy Rebamipide with PPIs increases the effectiveness of relief of GERD symptoms, as well as reduces the frequency of relapses.Conclusion. These clinical recommendations will improve the quality of medical care for patients with GERD.

Aim: to demonstrate the need for a detailed differential diagnosis and selection of therapy in a patient with decompensated liver cirrhosis of combined etiology (HCV infection and primary sclerosing cholangitis). Key points. The patient came to the clinic with complaints of shortness of breath with minimal physical activity, abdominal enlargement, swelling of the legs, yellowness of the skin, and severe weakness. The complaints arose two months after suffering from left-sided focal pneumonia. Laboratory tests revealed signs of systemic inflammation, liver failure, and acute kidney injury. According to the results of instrumental studies, massive hydrothorax was noted in the right pleural cavity. The patient underwent a series of thoracentesis, and a total of about four liters of non-inflammatory pleural fluid was evacuated. Differential diagnosis was based on the presence of dyspnea and respiratory failure. The patient received effective antiviral therapy with drugs using an interferon-free regimen. Subsequently, conservative therapy was carried out, against the background of which the symptoms regressed and the patient’s condition improved. Conclusions. Hepatopleural syndrome is a serious complication in patients with decompensated liver cirrhosis, although it does not always appear secondary to massive ascites. To resolve hepatic hydrothorax, it is necessary to carry out diuretic therapy, replacement transfusion therapy with albumin preparations, and if there is a large amount of fluid in the pleural cavities, therapeutic and diagnostic thoracentesis is recommended.

The aim of publication. Analysis of clinical cases demonstrating differentiated management approach at chronic H. pylori-associated gastritis with stomach epithelium dysplasia.Key points. Detection of high grade (severe) dysplasia is associated to high risk of early, invasive stomach cancer or its rapid development. In presented clinical case adenocarcinoma has been found in 60 year-old male patient with deep submucosa invasion simultaneously with high grade dysplasia. According to comprehensive endoscopic investigation endoscopic treatment option was considered impossible and patient underwent distal subtotal stomach resection with Roux-en-Y anastomosis and D2 regional lymph node dissection. At low grade (mild) dysplasia complex endoscopic investigation is recommended to identify local premalignant lesions of the stomach mucosa, and at ruling them out — to determine adequate therapy. So, in presented clinical case H. pylori eradication therapy in 45-year old patient has led to disappearance of changes suspicious to epithelial dysplasia. The term «indefinite for dysplasia» is applied to atypical changes which can be characterized as of premalignant or reactive nature. It is provisional conclusion which requires specifying endoscopy with guided biopsy and repeated histological conclusion.Conclusion. Prognosis and management approach in the cases with histological conclusion of stomach epithelium dysplasia should be determined according to comprehensive multimodal endoscopic investigation with guided biopsy.

Aim: to optimize outcomes of the treatment and prevention of gastrointestinal diseases in adults and children. Key points. The Methodological Guidelines contain sections on the terminology, classification, mechanisms of action, requirements for sale in the Russian Federation, requirements for proving the efficacy and safety of probiotics, prebiotics, synbiotics and metabiotics, as well as functional foods enriched with them. An overview of relevant data allowing to include these drugs and products in the treatment an d prevention of gastrointestinal diseases in adults and children is presented. Conclusion. The clinical efficacy of probiotics, prebiotics, synbiotics and metabiotics depends on the specificity and quantity of their components, the dosage form, the regimen and duration of treatment. Products and functional foods with proven efficacy and safety are recommended for the treatment and prevention of gastrointestinal diseases in adults and children.

Changes in body composition, in particular sarcopenia and sarcopenic obesity, are complications of liver cirrhosis affected by unfavorable parent substances. The selection of diet and exercise for at least 8 weeks allows you to get the best results when taken by patients with cirrhosis of the liver. The correlate of motor activity in the bioimpedance analysis of the active fraction of the active cell mass in the lean mass of the human body. Aim of the study. To assess the relationship between increased cell mass and the severity of ascites and hepatic encephalopathy in liver cirrhosis. Material and methods. 46 patients with liver cirrhosis were examined. The component composition of the body is felt with the help of ABC-01 "Medass" devices (STC Medass, Russia). Ascites was assessed during the clinical examination, as well as the results of the examination of the abdominal cavity and retroperitoneal space. Diagnosis of hepatic encephalopathy impact test on the speed of cognitive reaction: "Number connection test". Results. A significant relationship was found between the proportion of active cell mass and the severity of ascites (r = –0.312, p-value = 0.034), indicating that a decrease in active cell mass is a prognostically unfavorable disease for the progression of ascites in patients with liver cirrhosis. Correlation analysis showed the presence of a negative correlation average strength between the values of the share of AKM in TMT and high body weight of PE: r = –0.229 (p value = 0.125), which requires research on studies between the values of the relationship between active cell mass and body weight. hepatic encephalopathy. Conclusion. Sensitive relationships have been found between active cell mass and the severity of liver cirrhosis. Determination of body composition products, in particular the absolute and relative indicators of active cell mass, in patients with liver cirrhosis can be of practical use in compiling promising mathematical models of prognosis.

Aim: to evaluate the relationship of body composition components with the development of ascites in patients with liver cirrhosis.Materials and methods. One hundred and ten patients (44 men and 66 women) with the established diagnosis of liver cirrhosis were treated at the University Clinical Hospital No 2 of the Sechenov University. The assessment of the component composition of the patients’ body was carried out using the ABC-01 “MEDASS” device (“MEDASS”, Russia). Ascites diagnosis was performed using ultrasound examination of the abdominal cavity and retroperitoneal space.Results. The values of body mass index (p < 0.001), fat mass (p = 0.002), active cell mass (p < 0.001), and phase angle (p < 0.001) were lower in patients with ascites than without it. Patients with a lower percentage of body fat mass had a more severe ascites severity and vice versa, and the proportion of fat mass was generally higher in women than in men (r = –0.290; p = 0.002). Patients with lower active cell mass had higher ascites severity (r = –0.380; p < 0.001). However, this indicator was lower in women than in men. Significant negative correlations were revealed between fat mass, active cell mass, phase angle (r = –0.395; p < 0.001) and the severity of ascites.Conclusion. Our study confirms the importance of body composition parameters in the development of ascites in patients with cirrhosis of the liver. Insufficient amount of fat and muscle mass, as well as low values of the phase angle according to the results of bioimpedance can become predictors of the development of ascites. Evaluation of these components can be used in prognostic models to identify patients with an increased risk of ascites. Further research in this area will help to better understand the mechanisms of ascites development and develop effective methods of prevention and treatment of this complication in patients with liver cirrhosis.

Introduction. In cirrhotic patients, hyperammonemia develops due to impaired ammonia detoxification and portosystemic blood shunting and is most commonly associated with hepatic encephalopathy and sarcopenia. Currently, there are questions regarding the diagnosis of hyperammonemia and the effect of ammonia-lowering therapy on disease outcomes.Materials and methods. The Russian Scientific Liver Society selected a panel of seven experts in liver cirrhosis research and management of patients with this disease to make reasoned statements and recommendations on the issue of diagnostic and prognostic value of hyperammonemia in patients with liver cirrhosis, hepatic encephalopathy and sarcopenia.Results. The Delphi panel identified the most relevant topics, in the form of PICO questions (patient or population, intervention, comparison, outcome). The Delphi panel made six questions relevant to clinical practice and gave reasoned answers, framed as ‘clinical practice recommendations and statements’ with evidence-based comments. The questions and statements were based on the search and critical analysis of medical literature by keywords in Englishand Russian-language databases. The formulated questions could be combined into four categories: hepatic encephalopathy, sarcopenia, hyperammonemia, and ammonia-lowering therapy.Conclusions. The results of the experts' work are directly relevant to the quality management of patients with liver cirrhosis, and their recommendations and statements can be used in clinical practice.

Aim of review. The prognosis and management approach for chronic liver diseases of any etiology in many respects are determined by stage and extent of fibrosis which reflects activity, spread and duration of liver disease. Aim of current publication was to highlight these issues.Summary. Investigations in the field of fibrogenesis processes made possible quantitative estimation of liver fibrosis by non-invasive tests based both on assessment of peripheral blood levels of substances, directly involved in various stages of extracellular matrix synthesis and disintegration, and on the routine laboratory tests reflecting activity of inflammation, degree of disorder of synthetic liver function and fibrosis progression.Conclusion. Study of diagnostic accuracy of serum markers for assessment of fibrosis stage in liver disea ses of various etiology will provide development of comprehensive non-invasive test for estimation of treatment response rate, course and progression rate of disease

Introduction. The use of hypoammonemic agents to treat sarcopenia in liver cirrhosis has the potential to positively affect muscle mass, strength and function, given the pathogenetic basis of sarcopenia in liver cirrhosis.Aim. To compare muscle mass, strength and function, as well as capillary blood ammonia levels in patients with decompensated liver cirrhosis in two groups with and without use of L-ornithine-L-aspartate (LOLA).Materials and methods. A prospective cohort study was conducted. The treatment group included patients with decompensated liver cirrhosis of various etiologies and hyperammonemia, who received a hypoammonemic agent (LOLA) as part of complex therapy; the comparator group included patients with liver cirrhosis, hyperammonemia and sarcopenia, who did not receive LOLA. All patients underwent measurements of muscle mass (shoulder muscle volume, skeletal muscle mass indices (SMI) measured by dual-energy X-ray absorptiometry), strength (dynamometry, chair stand test) and function (short physical performance battery).Results. An analysis of clinical outcomes included 42 patients: 30 from the treatment group and 12 from the comparator group. In the treatment group, the proportion of patients with reduced muscle mass decreased from 76.67% to 73.33% (p = 0.012).The average shoulder muscle volume in the treatment group was 20.86 cm, which reached 21.35 cm (p = 0.072) at 3 months of therapy. The growth in shoulder muscle values and changes in the skeletal muscle indices for the upper limbs showed an increase in muscle mass. In the treatment group, mean muscle mass values measured by handheld dynamometry (HHD) increased from 20.53 to 22.48 kg at 3 months of therapy (p = 0.011). The increase in dynamometry scores demonstrated an increase in muscle strength during LOLA therapy. The increase in balance test scores determining muscle function was reported (p < 0.001). The capillary blood ammonia levels did not change significantly in both groups.Conclusion. The study showed a significant increase in muscle mass, strength and function in patients with liver cirrhosis and hyperammonemia, receiving LOLA as part of decompensated liver cirrhosis therapy.