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This paper introduces the recent European Aerosol Research Lidar Network (EARLINET) quality-assurance efforts at instrument level. Within two dedicated campaigns and five single-site intercomparison activities, 21 EARLINET systems from 18 EARLINET stations were intercompared between 2009 and 2013. A comprehensive strategy for campaign setup and data evaluation has been established. Eleven systems from nine EARLINET stations participated in the EARLINET Lidar Intercomparison 2009 (EARLI09). In this campaign, three reference systems were qualified which served as traveling standards thereafter. EARLINET systems from nine other stations have been compared against these reference systems since 2009. We present and discuss comparisons at signal and at product level from all campaigns for more than 100 individual measurement channels at the wavelengths of 355, 387, 532, and 607 nm. It is shown that in most cases, a very good agreement of the compared systems with the respective reference is obtained. Mean signal deviations in predefined height ranges are typically below ±2 %. Particle backscatter and extinction coefficients agree within ±2 × 10−4 km−1 sr−1 and ± 0.01 km−1, respectively, in most cases. For systems or channels that showed larger discrepancies, an in-depth analysis of deficiencies was performed and technical solutions and upgrades were proposed and realized. The intercomparisons have reinforced confidence in the EARLINET data quality and allowed us to draw conclusions on necessary system improvements for some instruments and to identify major challenges that need to be tackled in the future.

Aim: to provide the basic points of the Expert Panel of the Russian Gastroenterological Association with discussion of measures to improve diagnostics, treatment and management of chronic gastritis patients.Key points. In the Russian Federation in 2021 more than 30 million patients diagnosed with “Gastritis and duodenitis” were recorded (K29 in accordance with International Classification of Diseases-10). H. pylori incidence rate in the Russian population has reduced and presently is about 40 %. In chronic gastritis pattern H. pylori-associated gastritis has still dominated though gastritis percent after successful H. pylori eradication, reactive gastropathy (including reflux gastritis) and autoimmune gastritis, has increased. Endoscopic and histologic examinations serve as key diagnostic techniques that provide a means for assessing the ethiology of gastritis, topography and degree of atrophic changes, gastritis staging as per OLGA/OLGIM system that properly correlates with the risk of stomach cancer and determines endoscopic examination strategy. H. pylori eradication therapy of gastritis serves as an etiotropic treatment and makes it possible to prevent progression of atrophy and stomach cancer. Conventional triple therapy combined with bismuth tripotassium dicitrate allows for achieving optimal cure rates of H. pylori eradication. Addition of rebamipide to regimens of H. pylori eradication improves their efficiency. Rebamipide arrests symptoms of dyspepsia in the case of chronic gastritis and functional dyspepsia. The administration of rebamipide for chronic gastritis makes it possible to influence the syndrome of increased epithelial permeability and inflammation, which makes it advisable to study it as a means of preventing stomach cancer and the progression of atrophy in various types of chronic gastritis.Conclusion. Members of the Expert Panel has approved the algorithm of diagnosis and treatment of H. pylori-associated gastritis, gastritis after H. pylori eradication and H. pylori-negative gastritis at the diagnostic stage in the case of initial presentation and long-term follow-up when needed.

Aim: creation of diagnostic models including electrical, viscoelastic parameters of erythrocytes to distinguish fatty liver disease of mixed etiology (metabolic + alcoholic) from non-alcoholic and alcoholic fatty liver disease.Materials and methods. We examined 46 men with non-alcoholic fatty liver disease (NAFLD), 43 men with alcoholic fatty liver disease (AFLD), as well as 54 men with fatty liver disease (FLD) of mixed genesis (metabolic + alcohol-related); average age of the patients included in the study made 48.4 ± 9.6 years. The diagnosis was established on the basis of liver ultrasound findings and FLI liver steatosis index with a fibrosis grade of F1 or less (FibroScan® 502, Echosens, France). The electrical and viscoelastic parameters of erythrocytes were investigated by the diagnostic technique of dielectrophoresis using an electrooptical cell detection system.Results. The most significant parameters for differentiating fatty liver disease of mixed genesis (metabolic + alcoholic) from NAFLD using the Volcano plot have turned out to be cell polarizability at a frequency of 106 Hz (p = 6.49 ×10-5), erythrocyte cell membrane capacity (p = 0.00077), relative polarizability (p = 0.001), the levels of which were higher in patients with NAFLD. On the contrary, the index of red blood cells destruction at 105 Hz was higher in FLD of the mixed genesis (p = 0.047) and the crossover frequency was shifted to the high frequency range more than in NAFLD (p = 0.0005). The discriminant analysis has additionally revealed the significance of the degree of erythrocyte deformation at 5 ×105 Hz in distinguishing between mixed-genesis FLD and NAFLD. In differentiating FLD of mixed genesis from NAFLD, a diagnostic model incorporating the above red blood cells parameters has provided an AUC of 0.829 (confidential interval: 0.742–0.916), sensitivity of 80.9 %, and specificity of 83.3 %. Two indicators of red blood cells have been established that statistically significantly distinguish the mixed-genesis FLD from the AFLD (Volcano plot); these are the index of red blood cells destruction at a frequency of 5 ×105 Hz, which was higher with AFLD (p = 0.0007), and the capacity of cell membranes, the value of which prevailed in mixed-genesis FLD (p = 0.011). When distinguishing the mixed-genesis FLD from the AFLD, the combined model with the inclusion of three parameters of red blood cells, namely the index of red blood cells destruction at a frequency of 5 ×105 Hz, the capacity of erythrocyte membranes, and polarizability at a frequency of 106 Hz, has shown the highest levels of diagnostic accuracy, namely AUC = 0.751 (confidential interval: 0.611–0.908) with a sensitivity of 79.5 %, specificity of 74.7 %.Conclusion. The electrical and viscoelastic parameters of erythrocytes studied using the diagnostic technique of dielectrophoresis should be considered as promising biomarkers for the diagnosis of diffuse liver disease.

Aim. To study the characteristics of the fatty acid (FA) profi le of blood serum and erythrocyte membranes in patients with two forms of fatty liver disease (metabolic + alcoholic): steatosis and steatohepatitis with normal transaminase activity.Materials and methods. We examined 33 men (50.7 ± 9.6 years) with fatty liver disease (metabolic and alcoholic) with fi brosis F ≤ 1 (FibroTest). According to the ActiTest results, patients were divided into groups of steatosis – with minimal (A0–1) activity (n = 17) and steatohepatitis – with moderate/severe (A2–3) necroinfl ammatory activity (n = 16). The FA composition of blood serum and erythrocyte membranes was studied using gas chromatography/mass spectrometry Agilent 7000B (Agilent Technologies, Inc., USA). Methods of unpaired statistics using volcano plot and discriminant analysis based on orthogonal least squares (Orthogonal Partial Least Squares Discriminant Analysis, OPLS-DA), ROC analysis were applied.Results. Volcano plot analysis showed that in patients with fatty liver disease (metabolic and alcoholic) with normal transaminase activity, serum levels of stearic C18:0 (p = 0.016), arachidic C20:0 (p = 0.023), ratio saturated / polyunsaturated fatty acids (PUFA) (p = 0.001) were statistically signifi cantly higher in the steatohepatitis group compared with the steatosis group. The total content in the blood serum of all PUFA (p = 0.003), margaric C17:0 (p = 0.011), the sum of two omega-3 PUFA – eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3) (p = 0.04), the total content of all omega-3 PUFA (p = 0.042) were statistically signifi cantly lower in patients with steatohepatitis. OPLS-DA demonstrated fairly accurate separation of steatohepatitis and steatosis using individual FA and their ratios. When individual FA and their ratios were included in the analysis, a model was obtained with AUC = 0.827 (95% confi dence interval 0.499–1.0), sensitivity 82.2% and specifi city 80.7%.Conclusion. FA in blood serum and erythrocyte membranes appear to be promising biomarkers of steatohepatitis with normal levels of transaminases.

BACKGROUND: The diagnosis of liver fibrosis is an important task in the management of patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The currently used diagnostic methods have a number of disadvantages such as invasiveness and high cost, or insufficient sensitivity and specificity. Therefore, the search for new non-invasive markers of liver fibrosis remains an actual challenge.AIM: To assess a diagnostic value of serum growth differentiation factor-15 (GDF-15), microfibril-associated glycoprotein 4 (MFAP-4), collagen type IV alpha1 (COL4alpha1), Mac-2 binding protein (M2BPGI) and chitinase-3-like protein 1 (YKL-40) as markers of liver fibrosis in patients with type 2 diabetes and NAFLD.MATERIALS AND METHODS: A single center cross-sectional observational study was performed. The study included 74 patients, 23 men and 51 women, aged 18 to 74 years. Liver elastography was used as reference method for the fibrosis evaluation. APRI and fib-4, non-invasive fibrosis indices, were assessed. Serum concentrations of GDF-15, MFAP-4, COL4alpha1, M2BPGI, and YKL-40 were determined by ELISA. ROC analysis was used to evaluate the sensitivity and specificity of serum markers for the diagnosis of the liver fibrosis.RESULTS: Liver fibrosis stage 1 was verified in 16 subjects, stage 2 in 12, stage 3 in 7, and stage 4 in 19. Patients with advanced liver fibrosis (stages 3–4), compared with those without severe fibrosis (stages 0–2), had higher levels of GDF-15 (p=0.003), COL4alpha1 (p=0.007), and YKL-40 (p=0.04). Patients with stage 1-2 liver fibrosis had higher levels of COL4alpha compared to those without any signs of fibrosis (p=0.02). There were no significant differences in the level of MFAP-4 and M2BPGI between patients with different severity of fibrosis. According to the ROC analysis, GDF-15, COL4alpha1 and YKL-40 have diagnostic value in the detection of severe liver fibrosis comparable to that of the APRI and fib-4 indices.CONCLUSION: GDF-15, COL4alpha1 and YKL-40 could be considered as promising non-invasive markers of liver fibrosis in patients with type 2 diabetes and NAFLD.

Aim of the study was to estimate the blood serum level of microtubule-associated protein 1 light chain 3 alpha (MAP1LC3alpha), beclin-1 (BECN-1), Bcl-2 (BCL-2), caspase-3 (CASP3) and autophagy related 5 (ATG-5) protein as potential markers of liver fibrosis in type 2 diabetes (T2D) patients with non-alcoholic fatty liver disease (NAFLD).Material and methods. A single center cross-sectional observational study was performed. Seventy four patients with T2D and NAFLD were included, 23 men and 51 women, aged 18 to 74 years. Transient elastography was used for the assessment of liver fibrosis. The severity of fibrosis was estimated using the Metavir sсore. In addition, indirect liver fibrosis indices APRI and FIB-4 were calculated. Serum concentration of MAP1LC3alpha, BECN-1, BCL-2, CASP and ATG-5 was measured by ELISA. We applied ROC analysis to assess the value of studied indicators in diagnosis of liver fibrosis.Results. Liver fibrosis stage F1 was verified in 16 subjects, stage F2 in 12, stage F3 in 7, and stage F4 in 19 individuals. Patients with advanced liver fibrosis (stage 3-4) when compared to those without fibrosis (stage 0–2) had higher content of MAP1LC3alpha (p = 0.01) and BECN-1 (p = 0.01). There were no significant differences in the level of BCL-2, CASP3 and ATG-5 between patients with different severity of fibrosis. In the ROC analysis, MAP1LC3alpha and BECN-1 showed significance for the diagnosis of severe liver fibrosis, which, however, did not exceed that of the APRI index.Conclusions. In patients with T2D and NAFLD, serum levels of MAP1LC3alpha and BECN-1 are associated with severe liver fibrosis.

Aim: to present the results of an expert discussion of modern aspects of the clinical manifestations, pathogenesis and treatment of alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD).Key points. ALD and NAFLD are characterized by high prevalence and have a significant impact on public health. For the diagnosis of liver pathology, it is important to determine the stage of fibrosis and the severity of the exacerbation of the disease. In the treatment of ALD, it is recommended to achieve abstinence, proper nutrition, the appointment of B vitamins, drugs with cytoprotective activity. In severe hepatitis, corticosteroids may be prescribed. In the treatment of NAFLD, diet and lifestyle modification, weight loss, the use of insulin sensitizers, vitamin E, statins (in the presence of hyperlipidemia) and drugs with metabolic activity are effective.Currently, a point of view is being actively expressed about the synergism of the action of alcohol and the metabolic syndrome on the development of fibrosis, cirrhosis, and hepatocellular carcinoma. The current international consensus recommends a change in the nomenclature of NAFLD and ALD and proposes the terms “metabolically associated steatotic liver disease” and “metabolically associated alcoholic liver disease”.Conclusion. The closeness of the clinical manifestations and pathogenesis of NAFLD and ALD justifies attention to drugs with metabolic activity, which are recommended by the Russian Gastroenterological Association and Russian Scientific Liver Society for the treatment of these diseases. The experts support the suggestion to quantify alcohol consumption in patients with NAFLD in order to change the management of patients, if necessary.

Aim: bring to the attention of practitioners indications for anti-Helicobacter therapy, methods and procedure for diagnostics and eradication therapy of Н. pylori infection.Key points. Chronic gastritis caused by Н. pylori infection, including asymptomatic persons, may be considered as an indication for eradication therapy of Н. pylori as etiological therapy and opportunistic screening for gastric cancer prevention. Indications, for obligatory anti-Helicobacter therapy include peptic ulcer, gastric MALT lymphoma, early gastric cancer (EGC) with endoscopic resection. H. pylori primary diagnostics methods include 13C-urea breath test, H. pylori stool antigen lab test, rapid urease test and serological method. The serological method cannot be used after anti-Helicobacter therapy.In Russia H. pylori strains' resistance to clarithromycin does not exceed 15 % in most regional studies. The first line therapy for Н. pylori infection eradication is the standard triple therapy including a proton pump inhibitor (PPI), clarithromycin and amoxicillin, enhanced with bismuthate tripotassium dicitrate. A classic four-component therapy based on bismuthate tripotassium dicitrate or quadrotherapy without bismuth drug products which includes PPI, amoxicillin, clarithromycin and metronidazole, may be used as alternative to the first line eradication therapy. The standard triple therapy may be prescribed for 14 days only in those regions, where it has been proven to be effective. Quadrotherapy with bismuthate tripotassium dicitrate is also used as main second line therapy in case of standard triple therapy, bismuth enhanced standard triple therapy or combined therapy failure. Another second line therapy includes PPI, levofloxacin and amoxicillin, to which a bismuth-containing drug product may be added. The third line therapy is selected individually based on previously used treatment settings.Conclusion. In each case of H. pylori infection the decision for eradication therapy should be made, which is especially relevant as eradication of H. pylori has been recognized as an effective measure for the prevention of gastric cancer.

Background. First-line therapy does not always provide a high level of Helicobacter pylori eradication due to the increase of H. pylori resistance to antibiotics; therefore, it remains necessary to identify the most effective rescue treatments. The purpose of this study was to evaluate the efficacy and safety of empirical H. pylori furazolidone-containing regimens. Materials and methods. Adult H. pylori infected patients empirically treated with furazolidone-containing eradication regimens were registered in an international, prospective, multicenter non-intervention European registry on H. pylori management (Hp-EuReg). Data were collected at AEG-REDCap e-CRF from 2013 to 2021 and the quality was reviewed. Modified intention-to-treat (mITT) effectiveness analyses were performed. Results. Overall 106 patients received empirical furazolidone-containing therapy in Russia. Furazolidone was prescribed in a sequential scheme along with amoxicillin, clarithromycin and a proton pump inhibitor in 68 (64%) cases, triple regimens were prescribed in 28 (26%) patients and quadruple regimens in 10 (9.4%). Treatment duration of 7 days was assigned to 2 (1.9%) patients, 10-day eradication therapy in case of 80 (75%) and 14 days in 24 (23%) patients. Furazolidone was mainly used in first- (79%) and second-line (21%) regimens. The methods used to diagnose H. pylori infection were: histology (81%), stool antigen test (64%), 13C-urea breath test (6.6%), and rapid urease test (1.9%). The mITT effectiveness of sequential therapy was 100%; 93% with the triple therapy and 75.5% with quadruple therapy. Compliance was reported in 98% of cases. Adverse events were revealed in 5.7% of patients, mostly nausea (3.8%). No serious adverse events were reported. Conclusion. Furazolidone containing eradication regimens appear to be an effective and safe empirical therapy in Russia.

Aim: to study fatty acid levels in erythrocyte membranes (RBC) and blood serum (BS) in patients with inflammatory bowel diseases (IBDs) to develop differential diagnostic models including fatty acids as biomarkers to distinguish between nosological entities of IBDs (ulcerative colitis — UC, Crohn's disease — CD, unclassified colitis — UCC).Materials and methods. We examined 110 patients (mean age 37,7 ± 12,1 years) with IBDs and 53 healthy patients in control group (43,3 ± 11,7 years). The IBDs group included 50 patients with UC, 41 patients with CD, 19 patients with UCC. An exacerbation of the disease was revealed in 42 patients (84 %) with UC, 34 patients with CD (82.9 %) and 11 people with UCC (57.9 %). The study of fatty acids (FA) composition of RBC membranes and BS was carried out using GC/MS system based on three Agilent 7000B quadrupoles (USA).Results. The most significant for distinguishing active UC from CD exacerbation were serum levels of elaidin (p = 0.0006); docosatetraenoic (n-6) (p = 0.004); docodienic (n-6) (p = 0.009); omega-3/omega-6 ratio (p = 0.02); docosapentaenoic (n-3) (p = 0.03); the sum of eicosapentaenoic and docosahexaenoic (p = 0.03), as well as the content of RBC lauric FA (p = 0.04) (AUC — 0.89, sensitivity — 0.91, specificity — 0.89, diagnostic accuracy — 0.91). To distinguish active UC from the same of UCC, the following serum FA were found to be significant: alpha-linolenic; saturated (pentadecanoic, palmitic, stearic, arachidic); monounsaturated (palmitoleic, oleic); omega-6 (hexadecadienic, arachidonic) (p = 0.00000011—0.03300000) (AUC — 0.995, sensitivity — 0.98, specificity — 0.96, diagnostic accuracy — 0.97). The most significant in distinguishing patients with active CD from UCC exacerbation were levels of the following FA: alpha-linolenic; palmitoleic; oleic; the amount of saturated fatty acids (SFA); total unsaturated fatty acids (UFA); stearic; monounsaturated fatty acids (MUFA) amount; SFA/UFA; SFA/PUFA (polyunsaturated fatty acids); linoleic; total PUFA n6; lauric; arachidic acid (p = 0.0000000017–0.030000000) (AUC — 0.914, sensitivity — 0.90, specificity — 0.87, diagnostic accuracy — 0.91).Conclusion. The study of FA levels in groups with different nosological forms of IBDs using complex statistical analysis, including machine learning methods, made it possible to create diagnostic models that differentiate CD, UC and UCC in the acute stage with high accuracy. The proposed approach is promising for the purposes of differential diagnosis of nosological forms of IBDs.

Chronic liver disease (CLD), manifested as hepatic injury, is a major cause of global morbidity and mortality. CLD progresses to fibrosis, cirrhosis, and—ultimately—hepatocellular carcinoma (HCC) if left untreated. The different phenotypes of CLD based on their respective clinical features and causative agents include alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), metabolic-associated fatty liver disease (MAFLD), and drug-induced liver injury (DILI). The preferred treatment modality for CLD includes lifestyle modification and diet, along with limited pharmacological agents for symptomatic treatment. Moreover, oxidative stress (OS) is an important pathological mechanism underlying all CLD phenotypes; hence, the use of antioxidants to manage the disease is justified. Based on available clinical evidence, silymarin can be utilized as a hepatoprotective agent, given its potent antioxidant, antifibrotic, and anti-inflammatory properties. The role of silymarin in suppressing OS has been well established, and therefore silymarin is recommended for use in ALD and NAFLD in the guidelines approved by the Russian Medical Scientific Society of Therapists and the Gastroenterology Scientific Society of Russia. However, to discuss the positioning of the original silymarin in clinical guidelines and treatment protocols as a hepatoprotective agent for managing CLD concomitantly with other therapies, an expert panel of international and Russian medical professionals was convened on 11 November 2020. The panel reviewed approaches for the prevention and treatment of OS, existing guidelines for patient management for CLD, and available evidence on the effectiveness of silymarin in reducing OS, fibrosis, and hepatic inflammation and presented in the form of a narrative review.Key messagesAn expert panel of international and Russian medical professionals reviewed existing guidelines for ALD, NAFLD, MAFLD, and DILI to establish consensus recommendations that oxidative stress is the common pathophysiological mechanism underlying these conditions.The panel also discussed the positioning of original silymarin in clinical guidelines and treatment protocols as a hepatoprotective agent for managing CLD concomitantly with other therapies.The panel reviewed the effectiveness of 140 mg original silymarin three times a day in reducing oxidative stress in chronic liver diseases such as ALD, NAFLD, MAFLD, and DILI.

Aim: to present modern methods of diagnosis and treatment of chronic pancreatitis for gastroenterologists, general practitioners and physicians.Chronic pancreatitis (CP) is a long-term inflammatory disease of the pancreas, manifested by irreversible morphological changes in the parenchyma and pancreatic ducts, which cause pain and/or persistent impairment of function. Current concept on the etiology of CP is reflected by the TIGAR-O classification. The criteria for establishing the diagnosis of CP include typical attacks of abdominal pain and/or clinical and laboratory signs of exocrine, endocrine insufficiency with the mandatory detection of characteristic morphological changes (calcifications in the parenchyma and pancreatic ductal stones, dilatation of the main pancreatic duct and its branches). CT, MRCP, and pancreatobiliary endosonography are recommended as the methods of choice to verify the diagnosis of CP. Conservative treatment of patients with CP is provided for symptom relief and prevention of complications. Individual cases with severe non-interactable abdominal pain, as well as a complicated course of the disease (development of ductal hypertension due to main pancreatic duct stones or strictures, obstructive jaundice caused by compression of the common bile duct, symptomatic postnecrotic cysts, portal hypertension due to compression of the portal vein or thrombosis of the splenic vein, persistent duodenal obstruction, pseudoaneurysm of the celiac trunk basin and the superior mesenteric artery) serve as an indication for endoscopic or surgical treatment. The Guidelines set out modern approaches to the diagnosis, conservative, endoscopic and surgical treatment of CP, and the prevention of its complications.Conclusion. The implementation of clinical guidelines can contribute to the timely diagnosis and improve the quality of medical care for patients with chronic pancreatitis.

Aim. The clinical guidelines are intended to supplement specialty decision-making for improved aid quality in patients with gastritis and duodenitis though acknowledging the latest clinical evidence and principles of evidencebased medicine.Key points. Gastritis is an inflammatory disease of stomach mucosa, with a separate definition of acute and chronic gastritis. Chronic gastritis is a cohort of chronic diseases uniting a typical morphology of persistent inflammatory infiltration, impaired cellular renewal with emergent intestinal metaplasia, atrophy and epithelial dysplasia of gastric mucosa. Oesophagogastroduodenoscopy (OGDS) or high-resolution OGDS with magnified or non-magnified virtual chromoendoscopy, including targeted biopsy for atrophy and intestinal metaplasia grading and neoplasia detection, are recommended to verify gastritis and duodenitis, precancer states and/or gastric mucosal changes. All chronic gastritis patients positive for H. рylori should undergo eradication therapy as aetiological and subsidiary for gastric cancer prevention. Chronic gastritis patients with symptoms of dyspepsia (epigastric pain, burning and congestion, early satiety), also combined with functional dyspepsia, are recommended proton pump inhibitors, prokinetics, rebamipide and bismuth tripotassium dicitrate in symptomatic treatment. With focal restricted intestinal metaplasia, follow-up is not required in most cases, mainly when advanced atrophic gastritis is ruled out in high-quality endoscopy with biopsy. However, a familial history of gastric cancer, incomplete intestinal metaplasia and persistent H. pylori infection render endoscopy monitoring with chromoendoscopy and targeted biopsy desirable once in three years. Patients with advanced atrophic gastritis should have high-quality endoscopy every 3 years, and once in 1–2 years if complicated with a familial history of gastric cancer.Conclusion. The recommendations condense current knowledge on the aetiology and pathogenesis of gastritis and duodenitis, as well as laboratory and instrumental diagnostic techniques, main approaches to aetiological H. pylori eradication and treatment of dyspeptic states.

Similar abdominal pain of biliary type in functional disorders of biliary tract and chronic acalculous cholecystitis causes objective difficulties to differentiate not only between each other, but also with other diseases of gastrointestinal tract. The clinical picture is so homogeneous and difficult to distinguish from cholelithiasis that some patients undergo unreasonable surgical interventions for CAC and FDBT. Individual publications pushing for such an aggressive strategy are sporadic and need to be clarified in larger studies. The first choice drugs for treatment of FDBT are spasmolytics; ursodeoxycholic acid drugs are used as adjuvant agents. In CAC, the initial therapy will be similar, but the treatment regimen can be expanded with targeted etiotropic (if the cause of cholecystitis is identified – giardiasis, opisthorchiasis, etc.) or empirical antimicrobial/antiparasitic therapy. The greatest interest today is caused by hymecromone – a drug with proven by both experimental and controlled studies combined choleretic, selective spasmolytic action, mediated effect of reducing bile lithogenicity and possible anti-inflammatory action. Hymecromone effectively relieves biliary pain without causing gallbladder contractions, which determines the possibility of its wide application both in CAC and FDBT, both in monotherapy and in combination with other agents, primarily with UDCA. In this article the issues of optimization of diagnostic and therapeutic strategy of management of patients with biliary pain to avoid unreasonable cholecystectomies in acalculous diseases of the biliary tract are considered.

Aim. Current clinical recommendations are intended to supply gastroenterologists, physicians and general practitioners with modern methods for the diagnosis and treatment of constipation.Key points. Constipation is defined as primary (functional) and secondary form, the latter comprising a manifestation of another illness. The causes of constipation are diagnosed with colonoscopy, especially in patients aged over 50 having “anxiety symptoms” and hereditary colorectal oncological predisposition. Indications may also include the bowel transit time estimation with radiopaque markers, balloon expulsion test, anorectal manometry, defecography and electromyography. Therapy for constipation should be comprehensive and concern lifestyle, diet recommendations and use of medications (psyllium, macrogol, lactulose, lactitol, contact laxatives, prucalopride). Patients with a less effective conservative therapy and largely reduced quality of life should be considered for surgical intervention.Conclusion. An effective therapy for constipation requires a correct diagnosis of its causes.

Aim. Presentation of the Forum “Deprescribing and optimal selection of proton pump inhibitors” held in Moscow on 29 September 2020 during the 26th United Russian Gastroenterology Week.Key points. The Forum was aimed at discussing issues associated with improving the proton pump inhibitor (PPIs) therapy in treatment and prevention of acid-related diseases and upper gastrointestinal tract (GIT) disorders induced by non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet medications. Deprescribing is considered to be an effective strategy of a motivated reduction of the PPI dosage, duration of therapy and the patient’s transfer from a regular to on-demand intake regimen. The choice of PPI may condition an optimal therapy for acid-related diseases.Conclusion. PPIs prevail in therapies for acid-related diseases and NSAID-induced upper GIT lesions. PPI deprescribing should be a strategy of choice if medically indicated. A non-enzymatic metabolism, high acid suppression, stable antisecretory effect from day 1 of therapy and cytoprotective action justify the application of rabeprazole (Pariet®) for optimising therapies for acid-related diseases and implementing the deprescribing strategy.

Aim. To present the materials of an Expert Council, which was held on September 23, 2019 in Istanbul (Turkey) under the auspices of a World Gastroenterology Organisation congress and the support of the Abbott company.General provisions. During the work of the Expert Council, the role of motility disorders of the stomach and duodenum, intestines, gall bladder and the sphincter of Oddi in the development of functional diseases of the digestive system, such as functional dyspepsia (FD), irritable bowel syndrome (IBS), biliary dyskinesia (BD) was discussed, and the effectiveness of antispasmodics and prokinetics in their treatment was shown. At the same time, the advantages of the mebeverin antispasmodic drug, as well as the high efficiency and safety of the itopride hydrochloride prokinetic drug were noted. It is emphasized that, at the stage of a diagnostic search in the absence of “alarm symptoms” in patients with suspected FD, IBS, and BD, these drugs can be prescribed empirically.Conclusions. When selecting pharmacotherapy for patients with motor impairment, it is extremely important to consider the nature of these disorders. The use of modern medical preparations, which are characterized by a high level of safety and the targeted action towards a specific motility disorder, allows optimal therapy results to be achieved with minimal risks for the patient.

The multicenter prospective observational study initiated by the European Helicobacter and Microbiota Study Group (EHMSG) is conducted in 27 countries in Europe. The data from the Russian part of the European registry for the management of Helicobacter pylori infection (European Registry on the management of Helicobacter pylori infection, protocol: “Hp-EuReg”) allows us to analyze the real clinical practice of diagnosis and treatment of H. pylori and compare it with international recommendations. Materials and methods. A comparative analysis of the data entered in the register by the Russian research centers “Hp-EuReg”, in the period from 2013 to 2018, was conducted. Results and discussion. Invasive diagnostic methods prevail for the primary diagnosis of H. pylori [histology - 20.3% (in 2013 year) - 43.9% (in 2018 year), rapid urease test - 31.7% and 47.8% respectively]. The most popular mode of eradication therapy is a 10-day triple therapy (62.8-76.2%), the effectiveness of which does not exceed 79% (per protocol). Invasive tests (histology) are the leading method for control the effectiveness of therapy, however, there is a tendency towards a wider use of non-invasive methods (H. pylori stool antigen - from 17% in 2013 to 29.3% in 2018 and urea breath test from 6.9 to 18.3%, respectively). Serological test to control the effectiveness of eradication is still used from 8.2% (2013) to 6.1% (2018). Eradication therapy was not performed in 28% of patients throughout the entire observation period. Conclusion. In Russia, despite approved domestic and international recommendations, deviations in clinical practice persist, both during eradication therapy and in monitoring the effectiveness of eradication therapy.

Background: Epidemiological studies performed in different countries have identified a number of trends that allow to predict the problems related to the prevalence of inflammatory bowel diseases (IBD), their severity and healthcare resources utilization. Aim: To present comparative results of two large epidemiological studies of IBD in the Russian Federation (RF), i.e. ESCApe and ESCApe-2. Materials and methods: Two multicenter cross-sectional cohort studies with a similar design were performed at three-year interval. The studies had the common aim: to identify social and demographic and clinical particulars of ulcerative colitis (UC) and Crohn’s disease (CD) in RF, as well as treatment options. Twenty (20) centers of gastroenterology from 17 RF regions participated in the ESCApe (2010–2011) and 8 centers from 7 RF regions in the ESCApe-2 study (2013–2014). Results: The ESCApe study included 1797 patients (1254 UC and 543 CD), whereas the ESCApe-2 included 1000 patients (667 UC and 333 CD). Patient demographic and social characteristics: In both studies, female: male ratio was similar in UC and CD. Patients’ age was almost identical: in UC, median age was 38 years and 40 years in ESCApe and ESCApe-2, respectively; in CD the corresponding values were 36 and 35 years. In ESCApe, the peak UC onset was at the age of 21 to 40 years, whereas in CD it was shifted towards younger age (22.5% of the patients manifested before 20 years) and the peak incidence was in three age groups (below 20 years, 21 to 30 and 31 to 40 years). A statistically significant difference between CD and UC was found only in the age group of 11 to 20 years (22.5% vs. 13.6%, respectively, p < 0.01). In ESCApe-2, median age of disease onset in UC and CD was approximately 30 years. In both studies, urban:rural ratio for UC and CD was 4:1. In ESCApe, the proportion of current smokers among CD patients was almost two-fold higher than among those with UC (15.6 and 8.8%, respectively, p < 0.001); the same trend was found in ESCApe-2 (15 and 7.3%, p < 0.001). Socioeconomic characteristics of patients in both studies were similar: 50 to 60% were at work (professional occupation and income levels were not studied); in ESCApe 30.9% of UC patients and 40.9% of CD patients had legal disability due to various reasons (including that related to UC and CD in 12,6 and 14.9%, respectively), whereas in ESCApe-2 the respective proportions were 35.7 and 51.1%. Clinical characteristics of patients: The time from the first UC symptoms to diagnosis was similar in both studies (median, 5 months in ESCApe and 4 months in ESCApe-2); in CD patients these parameters were significantly different in both studies (12 vs. 1 month). As for the severity of the disease, the UC patients in ESCApe had mild disease in 16%, moderate in 53%, and severe in 31%, whereas the respective proportions among the CD patients were 21, 44, and 35%. In ESCApe-2, there were no patients with severe disease; mild and moderate UC were diagnosed in 51.3 and 46.6% of the patients, respectively, and mild and moderate CD, in 52.3 and 47.3%. The frequency of left-side UC was similar: 38% in ESCApе and 34% in ESCApе-2. Proctitis was more frequent in the first study (33 vs. 11%, p < 0.01), and total UC was more frequent in the second study (29 vs. 55%, p < 0.02). There were no significant differences between ESCApe and ESCApe-2 in the main CD localizations: terminal ileitis was seen in 31.3 and 35.4% of the patients, respectively, ileocolitis in 33.4 and 37.8%, colitis in 25.6 and 32.1%. The upper gastrointestinal involvement In ESCApе was found 4.4%, and mixed involvement in 5.3%. In both studies, extra-intestinal manifestations were more frequent in CD, than in UC: in ESCApe, 33.1% and 23% (р < 0.05), and in ESCApe-2 in 41.7 and 29.4%, respectively (р < 0.05). Peripheral arthropathies were most frequent. Ankylosing spondylitis was found in CD only, and primary sclerosing cholangitis, only in UC. Aphthous stomatitis was significantly more prevalent in CD in both studies. There were no significant differences in all other extra-intestinal symptoms (eye and skin involvement). Treatment characteristics: Treatment options before the study entry, as well as at the study inclusion visit were analyzed. In ESCApe, the majority of the patients had not been given any treatment before the study entry (49.1% with UC and 40.5% with CD). Three years later the situation was changing: in ESCApe-2, the proportion of treatment-naïve patients was 2.5 to 3-fold lower (15.3% with UC and 14.4% with CD), which was most probably related to increasing awareness of physicians. Before the study entry, most patients (40 to 70%) had been treated with 5-aminosalicylic acid (5-ASA). Before the second study, the patients were more frequently treated with glucocorticosteroids (GCS), immunosuppressors and genetically engineered biological agents (GEBA), but with no significant differences from the first study. 5-ASA prevailed also among the agents that were administered during the inclusion visits in both studies (80 to 90% UC patients and about 70% of CD patients). Compared to ESCApe, in ESCApe-2 there was a trend towards lower rate of GCS administration in UC and CD, but the differences did not reach the significance level. It may be explained by the absence of severe IBD types in ESCApe-2. In ESCApe, immunosuppressors were rarely used (in 14.4% of the UC patients and in 26.8% of the CD patients); however, in ESCApe-2 there were administered more frequently: up to 35.9% of the UC patients and 55.1% of the CD patients (р < 0.01 for both cases). It was unknown if immunosuppressors were used as monotherapy or in combination with GCS. Three years later, the rate of GEBA administration was also higher, but this increase was significant only in CD: 28.3% in ESCApe-2 vs. 9.2% in ESCApe (р < 0.01). According to the results of ESCApe, in the UC patients steroid resistance was seen in 23% and steroid dependency in 21%, whereas in the CD patients these values were 24 and 27%, respectively. In ESCApe-2 these parameters were not assessed. Conclusion: Both studies showed a number of patterns coinciding with the world trends, such as age and gender distribution of UC and CD patients, age at manifestation, the proportion of urban to rural residents, smoking status, prevalence and types of extra-intestinal symptoms. Unlike in European countries, moderate and severe forms of UC with extensive involvement are prevalent in RF. Low prevalence of mild and limited types of IBD is to be explained by underdiagnosis. Of note is the high proportion of patients with UC and CD treated with 5-ASA, although in CD these agents have demonstrated low efficacy. The rates of immunosuppressors and GEBA administration significantly increased in the second study, most likely, due to the implementation of a system of educational measures. Nevertheless, the rate of GEBA use in IBD remains low, which is to be related to their insufficient availability. In total, steroid resistance / steroid dependency rate amount to almost half of UC and CD cases. In general, some positive changes in the patient management are obvious in the second study. However, monitoring these changes over time could only be possible if similar studies would be performed at regular intervals.

Rationale: Recently, the incidence of inflammatory bowel disease (IBD) and non-alcoholic steatohepatosis has increased in developed countries. Also, there are fundamental prerequisites to mutually negative influence of these diseases. Therefore, evaluation of the characteristics of non-alcoholic steatohepatosis in patients with IBD is of practical interest. Aim: To identify particulars of non-alcoholic steatohepatosis / steatohepatitis in IBD patients. Materials and methods: This cross-sectional study included 245 patients aged from 18 to 77 years from the IBD Registry the Novosibirsk State Medical University and the State Scientific-Research Institute of Physiology and Basic Medicine (Novosibirsk, Russian Federation). Within one year before the study entry, the patients were assessed by abdominal ultrasound and diagnosed with steatohepatosis. All patients were examined clinically with measurement of their antropometric parameters and underwent laboratory assessments, including hematology tests, alanine and aspartate transaminases, creatinine, triglycerides and total cholesterol measurements. Patients with viral and autoimmune hepatitis, alcoholic liver disease, primary sclerosing cholangitis, iron and copper metabolism disorders were excluded. In the colon biopsy samples of 45 patients, Epstein-Barr virus, cytomegalovirus, herpes simplex virus were identified by polymerase chain reaction. One hundred and fifty two (152) patients were also assessed for small intestine bacterial overgrowth (SIBO) syndrome. Results: The prevalence of steatosis in patients with Crohn's disease (CD) was 34.2%, and in those with ulcerative colitis (UC), 30.4%. IBD patients with steatohepatosis were more likely to have received steroids (63.6% vs. 53%, p = 0.0006), had greater IBD du-ration (median 5.9 years, Q1/Q3, 2.7/12.9 years vs. 4.5, 2.9/8.5 years; p = 0.0324) and a higher body mass index (median 24.1, Q1/Q3, 21.4/29.9 vs. 21, 18.6/23.5; p = 0.0336). UC patients with non-alcoholic steatosis / steatohepatitis were older (odds ratio [OR] for the age above 40 years, 1.46; 95% confidence interval [CI] 1.01-2.1). CD patients with steatohepatosis had higher platelet counts (median 287 x 109/L, Q1/Q3, 192 x 109/L / 420 x 109/L vs. 250 x 109/L, 180 x 109/L / 379 x 109/L; p = 0.0183). SIBO was a risk factor for the development of steatohepatosis in IBD patients (OR 2.34, 95% CI 1.4-4.8, p = 0.021). Conclusion: The study has identified the differences in the steatohepatosis-associated factors in UC and CD patients. There is a link between the presence of SIBO and the risk of steatohepatosis development in IBD patients.

Aim: to assess the effectiveness of mebeverine 200 mg BID in patients with post-cholecystectomy gastrointestinal spasm not requiring surgical treatment. Materials and methods. 218 patients were included in 16 clinical centers in 14 cities in Russia. All patients had post-cholecystectomy gastrointestinal spasms, not requiring surgical treatment and received mebeverine (Duspatalin®) 200 mg BID. The observational assessment period lasted from the moment of their inclusion into the study up to 6 weeks post inlusion. The therapy results were evaluated using visual analog scales (GPA and 11-point numeric rating scale) by patient self-assessment of the dynamics of spasm/discomfort and other post-cholecystectomic gastrointestinal symptoms after 2 and 6 weeks of treatment. Gastrointestinal Quality of Life Index (GIQLI) was used to assess patient quality of life. Results and discussion. All 218 patients completed the 2-week mebeverine treatment course, 101 of them finished the 6-week course (“prolonged population”). Significant positive changes in the relief of abdominal pain and dyspepsia were noted as well as normalization of stool frequency and consistency. A more marked change in values was observed during prolonged (up to 6 weeks) therapy. Both 2-week and 6-week mebeverine courses led to a normalization of patient quality of life. After 6 week therapy, an effect of mebeverine on the quality of life 91% of patients was observed comparable to cholecystectomy itself, speficially related to the quality of life subscore ‘symptoms’. Conclusion. The results of our study demonstrate that mebeverine (Duspatalin®) therapy leads to an effective elimination of clinical symptoms associated with post-cholecystectomy GI-spasm disorders, like abdominal pain, symptoms of dyspepsia and stooldisorders. A more marked change in values was observed during prolonged (up to 6 weeks) therapy.

The Russian consensus on exo - and endocrine pancreatic insufficiency after surgical treatment was prepared on the initiative of the Russian "Pancreatic Club" on the Delphi method. His goal was to clarify and consolidate the opinions of specialists on the most relevant issues of diagnosis and treatment of exo - and endocrine insufficiency after surgical interventions on the pancreas. An interdisciplinary approach is provided by the participation of leading gastroenterologists and surgeons.

Aim of review. To present data of clinical trials, systematic reviews and metaanalyses which allow to optimize eradication therapy of Helicobacter pylori (H. pylori) infection. Summary. Standard triple therapy including proton pump inhibitor (PPI), clarithromycin and amoxicillin is the first­line treatment for H. pylori eradication. At prescription of standard triple therapy various measures increasing its efficacy should be utilized. Classical fourcomponent bismuth tripotassium dicitrate­based treatment or quadrotherapy without bismuth including PPI, amoxicillin, clarithromycin and metronidazole may be alternative options for the first line eradication therapy. Quadrotherapy with bismuth tripotassium dicitrate is applied as the basic mode of second line therapy at failure of standard triple therapy. Alternative mode of the second line therapy includes PPI, levofloxacin and amoxicillin. Levofloxacin­based triple therapy can be prescribed only by specialist in gastroenterology at strict indications. Third line therapy is personalized according to the choice of the previous treatment modes. The choice of H. pylori eradication therapy in the Russian Federation is based on empirical approach. The rate of clarithromycin resistance of H. pylori strains in Russia does not exceed 15% in the majority of regional studies. There are data indicating absence of significant metronidazole resistance of H. pylori and low level of double clarithromycin and metronidazole resistance. Efficacy of H. pylori eradication therapy may be enhanced by increasing treatment duration to 14 days. Prescription of new generation PPI or increase of PPI dose are targeted to provide the maximum acid suppression, highly important for successful H. pylori infection eradication. Additional prescription of bismuth tripotassium dicitrate, probiotics or rebamipid increases efficacy of antihelicobacter therapy. Significant decrease of adverse events rate at H. pylori eradication treatment is reached at combined prescription of probiotics. Rebamipid may potentiate reparative processes in the stomach mucosa. Conclusion: Methods of H. pylori eradication optimization can be applied for enhancement of both standard triple therapy and other concomitant treatment modes, and the combination of these methods provides best result for the given patient.

Aim of publication. To present indications for antihelicobacter therapy, methods and sequence of diagnostics and eradication treatment of Helicobacter pylori (H. pylori) infection to general practitioners. Key points. Chronic gastritis caused by H. pylori infection, including that in «asymptomatic» patients can be considered to be an indication for H. pylori eradication therapy both as etiological treatment and opportunistic screening diagnostics for gastric cancer prevention. Indications for obligatory antihelicobacter therapy include stomach and a duodenum peptic ulcer (PU), stomach MALT-lymphoma, early gastric cancer with endoscopic resection. Breath test with 13С-labeled urea, laboratory test for assessment of anti-H. pylori antibodies in feces, rapid urease test and serological method can be recommended for primary diagnostics of infection. Serological test is not applicable after antihelicobacter therapy. According to the bulk of regional studies clarithromycin resistance level of H. pylori strains in Russia does not exceed 15%. Obtained data indicate the absence of high metronidazole-resistance of H. pylori as well as double resistance to clarithromycin and metronidazole. Standard triple therapy including proton pump inhibitor (PPI), clarithromycin and amoxicillin is recommended as first-line treatment for H. pylori eradication. Standard triple therapy should be carried out, applying various means that increase its efficacy. Alternatively to standard triple therapy, first-line eradication treatment may include four-component bismuth tripotassium dicitratebased therapy or non-bismuth quadrotherapy which includes PPI, amoxicillin, clarithromycin and metronidazole. Quadrotherapy with bismuth tripotassium dicitrate can also be applied as a basic mode of the second line treatment at inefficiency of standard triple therapy. Alternative mode of second line eradication treatment includes PPI, levofloxacin and amoxicillin. Levofloxacinbased triple therapy prescription in the presence of strict indications should be limited to gastroenterologists. The third-line eradication treatment is adjusted individually according to the history of previous treatment modes. Eradication efficacy may be increased by prolongation of treatment up to 14 days, applicaiton of modern PPIs or increase of PPI doze, addition of bismuth tripotassium dicitrate or probiotic. Conclusion. In each case of H. pylori detection it is reasonable to consider eradication therapy that is especially actual as H. pylori infection eradication is recognized as effective method of stomach cancer prevention. H. pylori eradication optimization methods can be applied both to standard and alternative modes while combination of these approaches allows to achieve the best result in a given patient.

Aim of publication. To present the data of Advisory council which took place on August 19, 2016 in Poland (Krakow) with the participation of Adamed Russia company. Summary. Advisory council activity provided the algorithm of diagnosis and treatment of biliary sludge. At detection of gallbladder sludge in a patient with right hypochondrial pain it is necessary to carry out general examination to rule out the other diseases that may be dangerous (neoplastic, acute cholecystitis, pancreatitis). In the absence of other changes, besides biliary sludge, prescription of initial course of hymecromone combined to ursodeoxycholic acid (UDCA) is indicated. In the case of clinical improvement at primary therapy course it is necessary to continue UDCA treatment for 3 months. Primary treatment course that should include combination of hymecromone and UDCA is indicated for those patients with asymptomatic sludge, who have putty-like bile in the gallbladder or bile ducts. In the case over the other forms of asymptomatic sludge usually only diet limitations and follow up (abdominal US every six months) are indicated. At detection of the ultrasound signs, typical for chronic pancreatitis, according to the Cambridge diagnostic criteria, verification of the diagnosis by multidetector computer tomography according to the pancreatic protocol is mandatory. Selective antispasmodic medications (e.g. hymecromone) will be one of the basic pharmaceutical agents in this case, indications to endoscopic treatment should be evaluated, typically - by means of endoscopic ultrasound investigation). Conclusions. At of patient with the biliary sludge selective antispasmodic medications and UDCA should be widely applied, in some cases methods of endoscopic surgery as well.

Aim of investigation. To estimate efficacy and safety of two pharmacological forms of «Phosphogliv» (lyophilizate for intravenous administration and capsules) for the treatment of fatty liver degeneration of non-alcoholic etiology. Material and methods. Original study included overall 180 patients with nonalcoholic fatty liver disease that were randomized to the basic and control groups in the ratio of 2:1. The basic group patients received Phosphogliv 5 mg/day as intravenous bolus injection for 2 weeks, followed by oral intake of 2 capsules t.i.d. for 10 weeks (the total treatment duration was 12 weeks), control group patients received placebo in the same mode. Serum levels of inflammatory marker adiponectin, NAFLD fibrosis score, treatment effect on quality of life and safety of patients were monitored. Results. In 12 wks in patients with more significant cytolysis (threefold and higher serum alanine transaminase activity) and the rate of adiponectin level improvement on the background of Phosphogliv was 57.9% versus only 10.0% (p=0.019) in the placebo group. The mean NAFLD fibrosis score in the basic group remained almost unchanged, while in the control group negative dynamics was revealed, that resulted in statistically significant differences between groups (2.5±1.2 units versus 2.0±1.3 units respectively; р=0.009). At Phosphogliv injection already during the first 2 wks more pronounced improvement of subjective perception of dyspeptic symptoms was observed (mean score was 5.6±1.3 versus 5.1±1.4; р=0.021). When the treatment course was completed the basic group patients had higher mean score by «level of energy» scale (5.9±1.0 versus 5.6±1.0; р=0.034). Only sporadic adverse effects were found to the background of treatment, no statistically significant differences in their rate in were recorded. Dynamics of the basic physical parameters and laboratory tests was comparable as well. Conclusions. Treatment of non-alcoholic fatty liver disease that includes Phosphogliv provides reduction of steatohepatitis activity, retardation of fibrosis progression, improvement of overall disease prognosis and high satisfaction of patients at a favorable safety profile.

Aim of publication. To present the modern concept on etiology and pathogenesis of constipation, its classification, basic diagnostic and treatment methods to general practitioners. Summary. The prevalence of constipation in general population is quite high and averages 12 to 19%. Two types of constipation are usually distinguished: primary (functional) and secondary that is related to mechanical obstruction of the intestinal passage of bowel content, neurologic and endocrine diseases, systemic diseases of connective tissue, intake of drugs etc. At diagnosing of functional constipation early detection of «alarm symptoms» which require thorough patient investigation is important. Moreover, insufficient treatment response require step-by-step instrumental diagnostics. Constipation treatment has to be comprehensive and include general recommendations (intensification of physical activity, increase in dietary fiber in daily ration etc.), intake of psyllium, laxatives, including first of all of polyethyleneglycol, at insufficient response enterokinetic agents. Conclusion. Successful treatment of constipation requires correct detection of its cause, following essential dietary recommendations and stepwise application of pharmaceutical agents.

Aim of review. To present management approach for acid-related diseases in patients with Helicobacter pylori (H. pylori) infection, under long-term proton pump inhibitor therapy. Summary. There is no relation of gastroesophageal reflux disease (GERD) symptom severity, the pattern of relapses and treatment efficacy to the presence or absence of H. pylori infection; successful H. pylori eradication does not cause relapse of pre-existing GERD and does not induce its development. At the same time it is impossible to neglect the data on potential induction or aggravation of GERD after H. pylori eradication in separate population groups, including those in Asia. The presence of GERD could not prevent infection eradication in the presence of other indications (e.g., peptic ulcer, chronic gastritis). Monotherapy by proton pump inhibitors (PPI) in H. pylori-positive patients with GERD may lead to progression of gastric corpus atrophy that can be regarded as risk factor for stomach cancer development. H. pylori infection eradication promotes reduction of gastritis-like changes severity irrespective of maintaining of acid-suppressive treatment. The choice of specific PPI for treatment of patients with GERD and other acid-related diseases, carrying out H. pylori eradication therapy or substitution of one PPI agent to another are individualized and depend on the indications registered in the drugs administration instructions, features of its pharmacokinetics and pharmacodynamics, possible drug-to-drug interactions. Conclusion. Testing for H. pylori infection and carrying out the subsequent eradication therapy could allow to prevent progression of corpus mucosa atrophy in patients with acid-related disorders, first of all those with GERD, who received long-term PPI treatment. Estimation of duration of PPI treatment at acid-related disorders, and terms of H. pylori eradication therapy should be evaluated according to clinical guidelines and treatment protocols of these diseases taking into account age of the patient, clinical features, course of disease, presence of complications.

Aim of investigation. To estimate efficacy and safety of narlaprevir (NVR) with ritonavir (RTV), pegilated interferon (peg-IFN) and ribavirin (RBV) at treatmentnaïve and earlier treated noncirrhotic patients with chronic hepatitis C caused by the 1st virus genotype in double blind placebo-controlled 3rd phase study (PIONEER). Material and methods. The main group received NVR (200 mg od orally) in combination to RTV (100 mg) and pegIFN/RBV for 12 weeks that was followed by peg-IFN/ RBV for 12 weeks. Comparison group received pegIFN/ RBV for 48 weeks, for the first 12 weeks in combination to placebo. Results. The sustained virologic response in 24 weeks after treatment termination (SVR24) in the main group (NVR/RTV, PEG IFN/RBV)) was achieved in 89.1% (163/183) of treatment-naïve and 69.7% (69/99) of earlier treated patients. SVR24 was achieved in 86.5% (32/37) of patients with relapse after previous peg-IFN/ RBV treatment course. The viral load decreased for the mean of 5.3 log10 in 2 weeks and 5.9 log10 in 4 weeks of treatment in the main group vs 1.5 log10 in 2 weeks and 2.5 log10 in 4 weeks in comparison group. In treatment-naïve patients from the main group SVR24 was achieved in 90.8% at initial METAVIR F0-F2 liver fibrosis stage and in 75% at F3 liver fibrosis stage. In those who were previously treated by peg-IFN/RBV, in the main group SVR-24 was attained in 72.6% at liver fibrosis stage F0-F2 and in 53.3% with F3 liver fibrosis stage. NVR/RTV addition to peg-IFN/RBV treatment did not alter safety profile as compared to peg-IFN/RBV therapy. Conclusions. In PIONEER study the narlaprevir combination therapy was characterized by high efficacy, convenience of administration and favorable safety profile.

Aim of publication. To present proceedings of Advisory council on postcholecystectomy syndrome (August 25, 2017; Prague, Czech Republic) with support of the Adamed Group company. Summary. The Advisory council proposed algorithm for investigation and management of patients with postcholecystectomy syndrome (PCS). Gallstone disease (GSD) is diagnosed in 10-25% of the population of various age, with obvious trend to involvement of the younger patient categories in the last decades. The total number of GSD patients increases every decade no less than twice. Cholecystectomy remains the basic method of surgical treatment of symptomatic GSD. Nowadays laparoscopic cholecystectomy became universally popular and earned the status of the «gold standard» of surgical treatment. At the same time at asymptomatic GSD the watchful waiting approach avoiding active treatment is considered to be the most expedient. Biliary sludge and microlithiasis including cases undiagnosed at routine investigation can be one of important factors for development of the PCS. Pharmacological treatment of sphincter of Oddi dysfunction that develop at GSD/PCS include following of dietary recommendations, intake of selective spasmolytics, digestive enzymes and ursodeoxycholic acid. Conclusions. Follow-up program for the patient of the cholecystectomy should include regular assessment of clinical symptoms for duly diagnostics of acute and/or severe complications and associated diseases, that may require surgical treatment. Treatment has to include regular courses of selective antispasmodics, the presence of indications - prescription of bile acid supplements, when required - methods of endoscopic surgery.

On behalf of the scientific Committee and researchers Hp-EuReg European Registry on the management of Helicobacter pylori infection («Hp-EuReg») - a multicenter prospective observational study initiated by the European Helicobacter and Microbiota Study Group, conducted in 27 European countries in order to evaluate the real clinical practice of diagnosis and treatment of H. pylori and its comparison with international recommendations. Materials and methods. The analysis of 2360 patients entered in the register by the Russian centres of «Hp-EuReg» in 2013-2017, who were underwent 1st line eradication therapy. Results. The most common methods of primary diagnosis of H. pylori are histological (37.7%), rapid urease test (29.2%) and serology (29.7%). The duration of eradication therapy in 9.4% of cases was 7 days, in 65.3% - 10 days, and in 25.3% - 14 days. To control the effectiveness of treatment, H. pylori antigen in feces (31.3%), urea breath test (23.4%) and histological method (23.3%) were used. In 3.6% cases was used serology by mistake. In 17.3% of patients control was not carried out. The effectiveness of triple therapy with a PPI, amoxicillin, clarithromycin (per protocol) was 67.6%, with 7-day course, 81.1% at 10-day and 86.7% at 14-day course. Еradication rate of triple therapy with addition of bismuth (per protocol) reached 90,6% in the group receiving 10-day scheme and 93.6% in the group receiving the 14-day treatment. Conclusion. Significant deviations of clinical practice from expert recommendations, most pronounced at the stage of monitoring the effectiveness of therapy, were noted. The suboptimal efficacy of triple therapy is shown.

1Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow; 2A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow; 3Kazan State Medical University, Kazan; 4Kazan (Volga) Federal University, Kazan; 5Far Eastern State Medical University, Ministry of Health of Russia, Khabarovsk; 6Morozov City Children’s Clinical Hospital, Moscow Healthcare Department, Moscow; 7I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia, Saint Petersburg; 8Siberian State Medical University, Ministry of Health of Russia, Tomsk; 9M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow; 10Maimonides State Classical Academy, Moscow; 11V.I. Razumovsky Saratov State Medical University, Saratov; 12I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow; 13S.M. Kirov Military Medical Academy, Ministry of Defense of the Russian Federation, Saint Petersburg; 14Surgut State Medical University, Ministry of Health of Russia, Surgut; 15City Clinical Hospital Five, Moscow Healthcare Department, Moscow; 16Nizhny Novgorod Medical Academy, Ministry of Health of Russia, Nizhny Novgorod; 17Territorial Clinical Hospital Two, Ministry of Health of the Krasnodar Territory, Krasnodar; 18Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia, Saint Petersburg; 19Rostov State Medical University, Ministry of Health of Russia, Rostov-on-Don; 20Omsk Medical University, Ministry of Health of Russia, Omsk; 21Russian Medical Academy of Postgraduate Education, Ministry of Health of Russia, Moscow; 22Novosibirsk State Medical University, Novosibirsk; 23Stavropol State Medical University, Ministry of Health of Russia, Stavropol; 24Kemerovo State Medical University, Ministry of Health of Russia, Kemerovo; 25N.I. Pirogov Russian Research Medical University, Ministry of Health of Russia, Moscow; 26A.M. Nikiforov All-Russian Center of Emergency and Radiation Medicine, Ministry of Emergency Situations of Russia, Saint Petersburg; 27Federal Research Center, Krasnoyarsk Research Center, Siberian Branch, Russian Academy of Sciences, Research Institute of Medical Problems of the North, Krasnoyarsk; 28S.P. Botkin City Clinical Hospital, Moscow Healthcare Department, Moscow; 29Tver State Medical University, Ministry of Health of Russia, Tver The Russian consensus (a consensus document) on the diagnosis and treatment of chronic pancreatitis has been prepared on the initiative of the Russian «Pancreatic Club» under the Delphi system. Its aim was to identify and consolidate the opinions of Russian experts on the most topical issues of the diagnosis and treatment of chronic pancreatitis. The interdisciplinary approach involved the participation of leading gastroenterologists, surgeons, and pediatricians.

Aim. To assess the prevalence of bacterial overgrowth syndrome (BOS) and its risk factors in patients with inflammatory bowel diseases (IBD). Subjects and methods. The patients from the Novosibirsk IBD registry, who had undergone a hydrogen breath test (HBT) using a Gastro+ device, were examined. Results. In 93 IBD patients who had undergone a HBD, the prevalence of BOS was 48% (46.2% for ulcerative colitis and 51.2% for Crohn’s disease). There was a strong correlation between abdominal bloating, abdominal rumbling, and positive HBT results in both patient groups. During the HBT, the patients with BOS frequently complained of diarrhea, borborygmi, belching, and anxiety. Conclusion. The findings suggest that BOS is highly prevalent among patients with IBD. BOS is associated with clinical symptoms, such as abdominal bloating, abdominal rumbling, tearfulness, and irritability.

The excessive bacterial growth syndrome (EBGS) is a rather complicated, important and currently actively studied problem in the clinical practice. Currently there are no strict recommendations in respect of EBGS diagnostics. Respiratory tests have been extensively used of late that have various specificity and sensitivity. It’s difficult to diagnose and to conduct differential diagnostics of EBGS but important as well as it allows optimization of the patient therapy.

The aim of review. To present the diagnostic and treatment algorithm for abdominal pain at out-patient/ polyclinic healthcare institutions and to demonstrate potential of hyoscine butylbromide application during diagnostic process and for relief of abdominal pain at irritable bowel syndrome.Summary. From 20% to 50% of all admissions to medical institutions are related to abdominal spasms and pain caused by irritable bowel syndrome (IBS). According to the Clinical guidelines of the Russian gastroenterological association and abdominal pain management algorithm at outpatient reception, the doctor on the basis of interviewing, inspection and physical data first of all should exclude acute abdominal diseases (acute pain, parietal pain) requiring urgent examination by the surgeon or gynecologist and subsequent hospitalization. In the case of visceral pain the minimal range of laboratory and instrumental tests is indicated. If the history of visceral pain is more than 6 months and there are no alarm symptoms, doctor should define specific features of clinical presentation already during outpatient visit, taking into account pain location, that provides formulation of preliminary diagnosis. Epigastric pain (dyspepsia), biliary pain, abdominal pain which can be accompanied by impaired frequency and consistency of stool determine the further investigation plan. Implementation of diagnostic algorithm allows to distinguish the organic disease or to establishthe diagnosis of functional disease. Hyoscine butylbromide at short-term treatment will relieve abdominal spasm as a symptomatic agent. Course treatment effectively reduces intensity and frequency of abdominal pain at IBS. The rate of adverse events and tolerability of hyoscine butylbromide are comparable to that of placebo.Conclusion. Symptomatic treatment by antispasmodic drugs is justified from the moment of referral for medical aid to outpatient department. Hyoscine butylbromide can be prescribed for relief of acute and chronic pain at any stage of diagnostic process. Course intake of antispasmodics has proved its efficacy for pain relief at IBS.

Current approach to the problem of liver cirrhosis and management of patients is described. Basic pharmacological groups and drugs used in the treatment of patients with liver cirrhosis are characterized. The focus is on the relevance of competent selection of medicines for the treatment of comorbid diseases in patients with liver cirrhosis. Conclusion: at the stage of cirrhosis, symptomatic treatment approach - a timely and proper management of the symptoms and complications of liver cirrhosis - could extend patient's life and improve its quality.

Antibacterial drugs as many other drugs have side effects, one of which is antibiotic-associated diarrhea (AAD). In addition to light idiopathic forms the practicing clinicians faces AAD grave forms. The major causative agent of grave forms is bacterium Clostridium difficile. Clostridium-induced diarrhea is inclined to recurrences. In addition to etiotropic therapy of Clostridium infection probiotics are effective drugs for prevention and therapy of AAD.

The article describes difficulties of the celiac syndrome diagnostics, causes of diagnostic errors in various clinical examples are specified. This helps to perceive certain diagnostics programs and to select similar nosologic entities between which the differential diagnostics should be conducted.

Proton pump inhibitors (PPI) were successfully used for the treatment of acid-base disorders, in particular GERD, for the past 20 years. However, approximately 30% of patients with gastroesophageal reflux disease (GERD) do not adequately respond to standard PPI therapy due to the impact of many factors: patient-specific PPI metabolism in the liver, concomitant pathology of the digestive system, pharmacokinetic properties of traditional dosage forms of PPI. Persistence of GERD symptoms is particularly explained by the fact that the use of conventional single release PPI does not allow to fully control the cyrcadian rhythm of gastric secretion and should be taken twice a day before a meal, which has a negative effect on adherence. Thanks to dual delayed-release and longer presence in blood, dexlansoprazole MR showed high efficacy in the treatment and maintaining remission of various forms of GERD, as well as greater adherence to treatment.

The aim of review. To analyze accumulated world data on human fecal microbiota transplantation (FMT) at treatment of digestive diseases.Summary. Review highlights basic problems of fecal microbiota transplantation — i.e. new and, probably, promising trend in treatment of many diseases, where traditional methods do not provide due results. Main results of FMT received by the present time at certain digestive diseases are discussed. At the same time clinical application of FMT is related to the ethical φ-factor and lack of microbiologic studies.Conclusion. Progress in understanding of clinical value of faecal microbiota will transform concept of pathogenesis and treatment of set of diseases.