Today, nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) account for more than 50% of chronic liver diseases and cirrhosis in developed countries. The clinical significance of these pathologies lies in the formation of liver fibrosis and, therefore, in the increased risk of liver cirrhosis and hepatocellular carcinoma, which are life-threatening conditions. NAFLD is based on obesity and insulin resistance, whereas alcohol consumption is central to the etiopathogenesis of ALD. Recently, the role of the gut-liver microbiota axis in the genesis of NAFLD and ALD has also received increasing attention. Changes in qualitative and quantitative composition of intestinal microbiota and alterations of barrier function of intestinal mucosa can lead to entry of intraluminal antigens through portal vein system into the liver, inducing damage to hepatocytes and activation of proinflammatory processes. It is shown that in patients with CLD (NAFLD and ALD) there is an increase in the permeability of the intestinal mucosa and dysbiotic changes of the intestinal microbiome. The role of the gut-liver microbiota axis is well described in the genesis of NAFLD and ALD. Chronic alcohol consumption leads to increased colonies of Gram-negative bacteria in the intestinal mucosa and, therefore, to the accumulation of endotoxins (lipopolysaccharide components of bacterial cell membranes). Acetaldehyde produced by ADH of the intestinal epithelium stimulates tyrosine phosphorylation of tight cell contacts, increasing intestinal mucosal permeability, which leads to translocation of endotoxins into the portal bloodstream. Obesity is a major risk factor for NAFLD, which is also associated with dysbiotic changes in the intestinal microbiome. Obese individuals have increased Firmicutes, decreased Bacteroidetes, mediated reduction of short-chain fatty acid synthesis and increased intestinal wall permeability due to disruption of intercellular dense contacts, which leads to increased translocation of bacteria and endotoxins into the systemic bloodstream.

Steatohepatitises is an etiologically heterogeneous group of pathological changes in the liver, which are characterized by the inflammatory infiltration of the hepatic parenchyma with underlying fatty degeneration of hepatocytes. Whatever is the etiological cause, the clinical significance of steatohepatitis involves the formation of liver fibrosis and, as a result, an increased risk of developing liver cirrhosis and hepatocellular carcinoma, which are life-threatening conditions. It is common practice to identify the following etiological variants of steatohepatitis: metabolic (55–65% of cases), alcoholic (45–55% of cases) and drug-induced (approximately 5% of cases). The pathogenetic basis of metabolic steatohepatitis lies in the mechanisms of increased lipolysis, excess free fatty acid pool and reduced β-oxidation stemming from obesity and insulin resistance. Pathogenetic factors mediating the development of alcoholic steatohepatitis are the toxic activity of acetaldehyde and increased CYP2E1 activity. Intake of some hepatotoxic drugs increases lipogenesis in hepatocytes and disrupts the electron transport chain, which leads to the formation of liver steatosis followed by transformation into steatohepatitis. Whatever is the etiological varient, steatohepatitis is asymptomatic in the prevailing majority of cases. However, some patients may present complaints of weakness, discomfort, or indolent pain in the right hypochondrium. A detailed history taking is essential for the establishment of the etiological cause of liver damage. Laboratory tests allow to diagnose steatohepatitis in increased levels of hepatic transaminases, usually not exceeding 2–3 times the normal values. In addition to liver enzymes, increased levels of alkaline phosphatase and GGTP can also be observed in steatohepatitis. Ultrasound imaging is the most accessible instrumental tool in clinical practice to establish the primary diagnosis of hepatic steatosis. Indirect elastometry is an equally informative non-invasive method for diagnosing steatohepatitis, which allows to measure both the degree of steatosis (the function of determining the ultrasonic controlled attenuation parameter (CAP) and liver fibrosis.

Introduction. Functional dyspepsia (FD) and irritable bowel syndrome (IBS) overlap is an adverse clinical situation, as patients with this syndrome have more severe clinical manifestations resulting in significant reductions in quality of life. For now, there are no meta-analytical papers that would summarize the frequency of FD – IBS overlap using the revised Rome IV criteria. Objective. To organize data on the prevalence of FD – IBS overlap using the revised Rome IV criteria.Materials and methods. A search for studies was conducted in MEDLINE / PubMed, EMBASE, Cochrane electronic databases. The search depth was 6 years (from January 2016 to February 2021). The final analysis included original publications from peerreviewed periodicals that used the revised Rome IV criteria as a method for diagnosing FD and IBS in the adult population with detailed descriptive statistics allowing to include resulting data in the meta-analysis.Results and discussion. The final analysis included 6 studies involving 1,180 patients with PD and 600 patients with IBS. The generalized prevalence of IBS in patients with PD was 41.511% (95% CI: 22.203–62.288). The analysis was undertaken by using a random-effects model, as there was significant heterogeneity among results (p < 0.0001; I2 = 94.28%). The generalized prevalence of PD in patients with IBS was 38.791% (95% CI: 9.438–73.710). The analysis was undertaken by using a random-effects model, as there was significant heterogeneity among results (p < 0.0001; I2 = 99.25%).Сonclusion. The complete meta-analysis showed that the frequency of FD - IBS overlap using the revised Rome IV criteria is quite high and accounts for about 40%. At the same time, further large studies of more homogeneous structure are needed to verify these results and study the potential pathogenetic relationship between PD and IBS.

Objective: to evaluate the effectiveness of an esophagoprotector in reducing the risk of recurrent symptoms of gastroesophageal reflux disease (GERD) in patients who requiring temporary cancellation of therapy with proton pump inhibitors (PPIs). Material and methods. For the prospective comparative study there were selectively chose patients who had been taking PPIs for a long time (at least one month) for the underlying disease and who required temporary discontinuation of antisecretory therapy due to objective medical reasons. The study included patients with endoscopically and/or pH-metrically verified GERD, as well as histologically verified Barrett's esophagus. In the process of randomization of patients, two equal groups were formed, depending on the therapy received at the time of PPI withdrawal: group 1 received antacids on demand, group 2 received antacids on demand, as well as the esophagoprotector Alfasoxx at a dose of 10 ml four times a day (after each meal and at night). The follow-up period was two weeks. The patients recorded episodes of heartburn in their personal diaries. Results. The study included 60 patients (28 men and 32 women). The average age of the examined patients was 43.1 ± 5.3 years. By the end of the two-week follow-up period, the frequency of recurrent symptoms in group 1 was 36.7%, while in group 2 it was 13.3%. The use of the esophagoprotector Alfasoxx contributed to the significant regression of the risk of heartburn recurrence (odds ratio 0.2657; 95% confidence interval (CI) 0.07328-0.9637; p = 0.0438) in comparison with the group of patients who received only antacids in the on-demand mode. When analyzing the population of patients who had relapsed symptoms, it was demonstrated that the average number of heartburn episodes in group 1 was 6.18 (95% CI 4,1930-8,1706), and in group 2 – 4.50 (95% CI 0,7121-8,2879). Conclusion. This prospective comparative study demonstrated that the use of the esophagoprotector Alfasoxx helps to reduce the risk of relapse of GERD symptoms in patients requiring temporary cancellation of PPI therapy.

The article presents results of the study whose objective was efficiency assessment for application of ursodeoxycholic acid in the frameworks of minimization of hepatotoxic action of antibacterial drugs included in the composition of classical triple scheme of eradication therapy of Helicobacter pylori infection.

In the article we analysed the difficulties of differential diagnosis of portal hypertension, considers a clinical case that illustrates the presented theoretical material. In the presented clinical observation, the patient’s disease was manifested by bleeding from the varicose veins of the esophagus. In most cases, portal hypertension syndrome in practicing clinicians is associated with liver cirrhosis, however, it is necessary to remember about the possibility of developing subhepatic portal hypertension, in particular as a result of the formation of portal vein thrombosis. If there are signs of portal hypertension, it is necessary to specify the level of obstruction to blood flow, that is, the form of portal hypertension (subhepatic, hepatic, suprahepatic). Often, portal vein thrombosis can be formed due to undiagnosed blood diseases that occur without any clinical symptoms. The provided clinical example demonstrates a case of portal hypertension in the outcome of a chronic form of myeloproliferative syndrome. Portal cavernoma is quite rare and it is formed due to multiple small-diameter venous structures that gradually replace the occluded vessel with a system of collaterals proximal and distal to the portal vein thrombosis site. In the formation of the diagnosis the main are radiation research methods, but the conclusions should be considered only in conjunction with the clinical evidence. The clinical case is interesting because a large cavernoma of the portal vein in a patient with subhepatic portal hypertension was regarded as a «solid formation» according to magnetic resonance tomography. According to the literature data, cavernous transformation has an external similarity to the tumor process, which expands the range of differential diagnosis and requires the exclusion of oncological formations.

The article presents results of the study whose objective was efficiency assessment for application of ursodeoxycholic acid in the frameworks of minimization of hepatotoxic action of antibacterial drugs included in the composition of classical triple scheme of eradication therapy of Helicobacter pylori infection.

Введение. В ряде исследований была выявлена достоверная ассоциация между низкой эффективностью эрадикационной терапии инфекции Helicobacter pylori (H. pylori) и избыточной массой тела или ожирением у пациентов без сахарного диабета. Данный тренд может объясняться различиями в профиле фармакокинетики ингибиторов протонной помпы, входящих в состав схем эрадикации.Цель исследования: оценить эффективность эрадикационной терапии инфекции (H. pylori) при использовании препаратов омепразола и рабепразола у пациентов с избыточной массой тела и ожирением.Материалы и методы: в проспективное рандомизированное сравнительное исследование было включено 34 пациента (21 мужчина и 13 женщин) с H. pylori -ассоциированной патологией и избыточной массой тела или ожирением (согласно классификации ВОЗ). В процессе рандомизации пациентов было сформировано 2 равные группы в зависимости от назначаемой схемы ЭТ. Первая группа (n = 17) получала классическую тройную схему ЭТ с омепразолом (омепразол 20 мг х 2 раза в стуки, амоксициллин 1000 мг х 2 раза в стуки, кларитромицин 500 мг х 2 раза в сутки) в течение 10 дней. Второй группе (n = 17) назначалась классическая тройная схема ЭТ с рабепразолом (рабепразол 20 мг х 2 раза в стуки, амоксициллин 1000 мг х 2 раза в сутки, кларитромицин 500 мг х 2 раза в сутки) в течение 10 дней. Скрининг и контроль эрадикации инфекции H. pylori производились при помощи быстрого уреазного теста биоптата или С13-уреазного дыхательного теста. Оценка эффективности ЭТ осуществлялась не ранее чем через 6 недель после окончания курса лечения.Результаты: Средний возраст пациентов составил 41,9 лет (95% ДИ: 36,5-47,2), а медиана ИМТ - 28,1 кг/м2 (95% ДИ: 26,9-32,0). Эффективность ЭТ в первой группе составила 64,7% (ITT), 73,33% (PP), а во второй группе - 82,35% (ITT), 87,5% (PP). Использование рабепразола в схеме классической тройной ЭТ потенцирует эффективность лечения у пациентов с избыточной массой тела и ожирением в выборке ITT (ОШ 2,54; 95% ДИ: 0,51-12,54) и PP (ОШ 2,54; 95% ДИ: 0,39-16,55) в сравнении с применением омепразола. При отборе для анализа исключительно пациентов с ожирением (ИМТ ≥ 30 кг/м2) в выборке PP эффективность ЭТ в первой группе составила 50,0%, а во второй - 83,33%.Заключение: проведенное исследование и данные литературного анализа позволяют сделать вывод, что тактика оптимизации ЭТ инфекции H. pylori с использованием рабепразола в качестве ИПП является наиболее многообещающей стратегией повышения эффективности лечения, особенно в группах риска неэффективного лечения, к которым относятся пациенты, страдающие избыточной массой тела и ожирением.

Purpose – the systematization of data on the resistance of Helicobacter pylori to clarithromycin in the Russian Federation. Material and methods. Necessary investigations were searched in the electronic databases MEDLINE/PubMed, EMBASE, Cochrane, and the Russian Science Citation Index (RSCI), published between January and September, 2020. The final analysis included original publications from periodically reviewed foreign and Russian publications, as well as dissertations that used validated H. pylori resistance assessment tests with detailed descriptive statistics that allow the resulting data to be included in the meta-analysis. Results. The final analysis included 16 studies (1227 isolates). The generalized indicator of H. pylori resistance to clarithromycin in the Russian Federation was 11.85% (95% confidence interval (CI) 7.315–17.302; I2 = 86.19%). When analyzing papers published over the past ten years, H. pylori resistance to clarithromycin was 10.39% (95% CI 7.103–14.219; I2 = 61.29%). In Moscow and the Moscow Region, the generalized indicator of H. pylori resistance to clarithromycin was 10.87% (95% CI 7,280–15,439; I2 = 50.57%), in St. Petersburg – 22.26% (95% CI 9,525–38,470; I2 = 84.75%), Smolensk – 5.74% (95% CI 3,511–8,789; I2 = 0.00%), Kazan – 10.0% (95% CI 5,023–17,355; I2 = 45.22%). Conclusion. The results show that the resistance of H. pylori to clarithromycin in Russia does not exceed the 15% threshold regulated by the Maastricht-V Consensus, which allows us to consider a triple regimen of anti-Helicobacter therapy with clarithromycin as a first-line therapy. At the same time, to achieve the maximum effect when using classical triple therapy and to level the risk of further progression of clarithromycin resistance of H. pylori in Russia, it is advisable to use methods of its optimization.

The review article presents current data on functional disorders of the biliary system, taking into account the latest recommendations of experts of the Rome Foundation (Rome Criteria IV, 2016) and the Russian Gastroenterological Association (specialized clinical recommendations, 2018). According to modern concepts, biliary dysfunction is a group of functional disorders of the biliary system caused by motor disorders and increased visceral sensitivity. According to the literature data, the prevalence of functional disorders of GB and OS is 10-15%, and violation of OS function is revealed in 30-40% of patients who underwent cholecystectomy (CE). The presence of biliary pain is an obligatory condition in the diagnosis of functional disorders of GB and OS. Bilirubin and serum transaminases (AST, ALT) levels may increase in biochemical blood analysis in patients with functional OS disorder of biliary type, and pancreatic amylase and lipase in case of functional OS disorder of pancreatic type. Ultrasound examination of abdominal organs is considered to be the priority among instrumental methods. This technique allows to exclude organic lesions of both the GB and visualized ducts, and adjacent organs (GSD, biliary tract, liver and pancreas neoplasms). Magnetic resonance cholangiopancreatography (MRCP) is used as a clarifying method, which allows to visualize the state of biliary ducts throughout. Ultrasonic cholecystography is used to assess the contractile activity of the GB. When duct dilation is detected and/or when liver/pancreatic enzyme levels are elevated in the absence of changes according to MRCP data, it is reasonable to perform an endoscopic ultrasound examination. According to the latest recommendations of the Russian Gastroenterological Association (2018), the foundation of pharmacotherapy for this group of diseases are antispasmodics and ursodeoxycholic acid (UDCA).

To date the mechanisms of etiopathogenesis of functional gastrointestinal diseases continue to be actively studied. By now, alteration of the components of the intestinal epithelial tight junctions supporting the intestinal barrier integrity has been identified in several studies in patients with irritable bowel syndrome and functional dyspepsia (FD). Characteristic changes in patients with IBS compared with healthy controls include decreased expression of ZO-1 protein and occludin in mucosal biopsy specimens from various parts of the colon. On the other hand, the analysis of duodenal biopsy specimens shows similar changes in patients with FD. The causative factor of these changes continues to be studied. In fact, experimental and clinical studies conducted to date have demonstrated that there are factors that affect adversely the structural and functional stability of intestinal tight junctions. Regardless of the initiating factor, the compromise of tight junctions results in the breach of permeability of the intestinal mucosa and the entry of various intraluminal factors into the proper mucous plate, contributing to the activation of resident immunocompetent cells. Due to the production of cytokines and other biologically active substances, the latter lead to sensitization of nerve endings, thereby inducing the development of visceral hypersensitivity phenomenon and alteration of the motor behaviours of the gastrointestinal tract. The literature describes the phenomenon of activation of a local inflammatory response in patients with functional gastrointestinal diseases as “low-grade inflammation”. These data update the need to consider restoration of the intestinal mucosal barrier in patients with diseases in question as a therapeutic target. This review article systematizes data on this problem.

AIM:Assessment of the diagnostic accuracy of predictive indexes of liver fibrosis for the identification of severe fibrosis and cirrhosis (F3F4) in patients with chronic hepatitis C (CHC).MATERIALS AND METHODS:The retrospective design study included 127 patients with chronic hepatitis C (mean age 44.511.1 years). To assess the degree of liver fibrosis, all patients underwent transient elastography using a Fibroscan (EchoSens, France) and predictive indexes of liver fibrosis were calculated (APRI, FIB-4, discriminant Bonacini score). Transient elastography was considered as a reference method for assessing the degree of liver fibrosis for subsequent comparison of results with predictive fibrosis indixes.RESULTS:The sensitivity of the APRI index for the identification of severe fibrosis and cirrhosis of the liver (F3F4) was 79%, and specificity was 69%. The FIB-4 index showed greater specificity (86%), but less sensitivity (68%). The sensitivity of the discriminant Bonacini scale was 81%, and the specificity was 77%. The positive predictive value of the APRI index, FIB-4 and the Bonacini scale for the identification of severe fibrosis and cirrhosis of the liver (F3F4) in patients with chronic hepatitis C was 66; 78 and 72% respectively, and negative predictive value 82; 78 and 84% respectively.CONCLUSION:The results of this study indicate the relatively high diagnostic accuracy of a number of predictive indexes for evaluating liver fibrosis (APRI, FIB-4, discriminant Bonachini scale) in identifying severe fibrosis and cirrhosis of the liver (F3F4) in patients with chronic hepatitis C.

Gastroesophageal reflux disease (GERD) is one of the most common pathologies in modern clinical practice. Laryngopharyngeal reflux (LPR) is considered to be an extraesophageal manifestation of GERD and is characterized by retrograde ingestion of gastric content into the larynx and pharynx, leading to recurrent otolaryngological symptoms. Classical manifestations of LPR are hoarseness, perspiration, dryness and feeling of lump in the throat, coughing. There is no «gold standard» for the diagnosis of LPR. At the same time, several instrumental methods are used in clinical practice to verify the diagnosis: laryngoscopy and EGDS are the most common, and in some cases - 24-hour pH-metry and impedancemetry. In the case of an established diagnosis of LPR, it is recommended to use a standard dosage of PPI twice a day for 3–6 months.

AIM:Evaluation of the efficacy and safety of quadrupletherapy without bismuth (concomitant therapy) in patients with Helicobacter pylori - associated gastric ulcer and duodenal ulcer in the framework of a comparative research in the population of patients in Russia.MATERIALS AND METHODS:A prospective randomized trial was conducted, which included 210 patients with H. pylori - associated gastric/duodenal ulcer without complications. During the process of randomization, the patients were divided into three equal groups (n=70) depending on the prescribed 10-day scheme of eradication therapy (ET): the first group received the classic triple scheme (Omeprazole 20 mg 2 times a day, Amoxicillin 1000 mg 2 times a day and Clarithromycin 500 mg 2 times a day); the second group received quadruple therapy with bismuth drugs (Omeprazole 20 mg 2 times a day, Tetracycline 500 mg 4 times a day, Metronidazole 500 mg 3 times a day, Bismuth subcitrate potassium 120 mg 4 times a day); the third group received quadruple therapy without bismuth - concomitant therapy (Omeprazole 20 mg 2 times a day, Amoxicillin 1000 mg 2 times a day, Clarithromycin 500 mg 2 times a day and Metronidazole 500 mg 2 times a day). Diagnostics of H. pylori infection during screening and control of eradication was carried out via the fast urease biopsy sample test and urea breath test system. Control of the effectiveness of ET of the microorganism was carried out not earlier than 4 weeks after the end of the treatment. During the course of therapy, the frequency of development of side effects was assessed using a special questionnaire.RESULTS AND DISCUSSION:The effectiveness of triple therapy was 72.8% (ITT; 95% CI of 62.17-83.54) and 78,4% (PP; 95% CI 68.19-88.72); quadruple therapy with the preparation of bismuth - 80.0% (ITT; 95% CI 70.39-89.6) and 84,8% (PP; 95% CI, 75.96-93.73); quadruple therapy without bismuth - concomitant therapy - 84.2% (ITT; 95% CI 75.54-93.02) and 92.1% (PP; 95% CI 85.43-98.94). Quadruple therapy without bismuth was reliably more effective than the classical triple therapy in the PP selection (p=0.044883). Statistical analysis showed a tendency to poorer effectiveness of ET in patients who had previously used antibiotic therapy (OR 0.4317; 95% CI 0.1776-1.049), and in individuals with a rapid metabolism genotype - CYP2C19*1/*1 (OR 0.12; 95% CI 0.005848-2.4624). The frequency of development of side effects during the use of triple therapy was 18.5% (95% CI of 9.23-27.91), when using quadruple therapy with bismuth - 20.0% (95% CI 10.39-29.6), and with the use of quadruple therapy without bismuth - concomitant therapy - 24.2% (95% CI 13.98-34.58).CONCLUSION:This prospective randomized study demonstrated the high efficiency of quadruple therapy without bismuth (concomitant therapy) in the framework of eradication of H. pylori infection in Russia.

Identification of changes in biochemical parameters of liver functional activity during screening studies requires additional examination of the patient in order to determine the genesis of the disease. In recent years, in routine practice, the most frequently used is an isolated definition of the level of transaminases (ALT, AST), which does not allow timely detection of latent cholestasis syndrome. Primary biliary cholangitis (PBC), previously referred to as primary biliary cirrhosis, is a relatively rare chronic autoimmune cholesthetic liver disease, predominantly affecting middle-aged women and prone to progressing liver cirrhosis. The recommendations of AASLD and EASL note the need for long-term monitoring of patients with ongoing UDCA therapy and regular diagnostic studies to identify signs of disease progression. A clinical example of successful treatment of a patient with PBC with the Russian drug Exhol® is described.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is characterized by periodic abdominal pain associated with altered bowel habits and/or changes in stool consistency. The chronic course of the disease marked by alternating periods of exacerbation and remission necessitates the long-term use of non-drug and pharmacological methods for the treatment of IBS, which is extremely negative for the patient’s compliance. A strategy for improving compliance of a patient with IBS is the cornerstone that allows a physician to ensure the optimal level of effectiveness of the prescribed therapy and minimize the risk of disease recurrence.

Diabetes mellitus (DM) is a moderately common issue both in the world and in the Russian Federation. Consequently, an interdisciplinary approach to studying the characteristics of the course and therapeutic management of gastroenterological pathology in this group of patients, in particular, Helicobacter pylori infection, which is associated with a whole range of diseases of the upper gastrointestinal tract, is of special interest. The article provides a systematic review of foreign and domestic studies of the efficacy and safety of various eradication regimens for Helicobacter pylori infection in patients with diabetes. In general, it was shown that the weighted average efficiency of eradication in people with diabetes was 17.7–23.8% lower than in people, who did not suffered from that disease.

Московский государственный медикостоматологический университет им.А.И

Functional dyspepsia (FD) is one of the most common gastroenterological diseases. The article presents modern views on the pathogenesis of the disease. It is shown that disorders of motor skills (retardation of voiding function, disturbance of relaxation accommodation) and stomach sensitivity (visceral hypersensitivity to stretching) are considered to be one of the main pathophysiological mechanisms of FD. The authors present a modern algorithm of treatment of patients with FD, based on the clinical recommendations of the Rome Consensus IV revision (2016) and the Russian Gastroenterological Association (2017). The strategy of differentiated use of pharmaceuticals for different variants of FD is considered.