Aim of review. To present rational on expediency of Helicobacter pylori (H. pylori) eradication for erosions and ulcers that develop on the background of nonsteroid anti-inflammatory drugs (NSAIDs) therapy. Summary. According to the data of Maastricht consensus (2012), H. pylori infection and NSAIDs are the two major independent etiological factors of peptic ulcer development and upper gastro-intestinal bleeding. However the effect of H. pylori and NSAIDs on gastrointestinal diseases remains uncertain. This is a crucial question as the most of patients (in the Russian population over 50%), that require NSAIDs and low doses of aspirin (LDA) are infected by H. pylori. According to series of studies, H. pylori is significantly more common in patients with NSAID-related gastropathy. H. pylori eradication is capable to decrease the risk of gastrointestinal diseases if carried out prior to NSAIDs prescription. At the same time, severe complicated forms of gastrointestinal diseases are common in H. pylori-negative patients, and H. pylori eradication in patients with NSAID-associated ulcers or ulcer bleeding does not provide essential decrease in recurrence rate at ongoing NSAID intake. In the analysis of large-scale NSAID safety studies no significant difference in endoscopic ulcer rate in the groups of H. pylori-infected and H. pylori-negative patients were detected. Available data allow to conclude that anti-H. pylori therapy requires differential approach in patients with indications for NSAID and LDA treatment. Conclusion. Diagnostics of H. pylori infection and eradication is indicated at development of severe complications (ulcer, bleeding), however they should not be used in routine practice at treatment in patients with low risk of complications. Anyway, H. pylori eradication does not eliminate necessity of other methods for NSAID gastropathy prophylaxis: application of COX-2 selective inhibitors and PPI preventive prescription.

Aim of investigation. To study the prevalence of CagApositive Helicobacter pylori (H. pylori) strain and to estimate activity of gastritis associated to this infection in schoolchildren presenting their dyspeptic complains in indigenous and extraterrestrial populations of Tuva republic. Material and methods. In 218 randomly selected schoolchildren (106 of them were extraterrestrial, 112 - native born) of overall 1064 children living in two settlements of the Tuva republic prevalence of CagA-positive H. pylori strain was studied. Inflammatory activity of the stomach body and antrum mucosa was studied in 59 Tuvinians and 72 Caucasians included in the study, according to predefined age groups (7-11 and 12-17 years). Results. Increase in the rate of CagA-seropositive children in local population was found to a large extent due to expense of junior children. Age-related increase in CagA-positive H pylori infection in specific ethnic group was insignificant. Antrum mucosa information in CagAseropositive children of extraterrestrial population was characterized by higher activity irrespective to age. That is not found in indigenous population. At CagAseropositive schoolchildren in both ethnic populations activity of corpus gastritis increased along with age. Conclusion. The received results demonstrate that development, course and progression of CagA-positive H. pylori associated gastritis is affected by genetic (ethnic) features of the host.

Aim of investigation. To determine antimicrobial susceptibility of H. pylori in Smolensk in 2015-2016. Material and methods. Overall 248 adult patients with positive rapid urease test at the time of gastroscopy were included in the study. Antimicrobial susceptibility testing of H. pylori isolates to clarithromycin, amoxicillin, metronidazole, levofloxacin, rifampicin, tetracycline was performed by the agar dilution method. Results. H. pylori was isolated in 33% (n=82) of patients (24 isolates were nonviable after freezing). The rates of resistance among tested isolates of H. pylori were: 3,5% (2/58) for clarithromycin, 3,5% (2/58) for amoxicillin, 10.3% (6/58) for metronidazole, 27,6% (16/58) for levofloxacin, 8.6% (5/58) for rifampicin. No isolates showed resistance to tetracycline. Among 58 H. pylori isolates 29% (17 isolates) were resistant to one antimicrobial agent, 12,1% (7 isolates) were resistant to two antimicrobial agents. Associated resistance was observed for levofloxacin and metronidazole 3,5% (2 isolates), levofloxacin and rifampicin 5,2% (3 isolates), metronidazole and rifampicin 3,5% (2 isolates). Conclusions. Smolensk is the area of low clarithromycin resistance. So, clarithromycin-containing regimens are recommended for first-line empirical eradication therapy. Use of levofloxacin is questionable in relation to high levels of resistance H. pylori to levofloxacin. Use of rifabutin is questionable in relation to relatively high H. pylori rifampicin resistance rate.

Aim of investigation. To evaluate motor function disorders of the large intestine and visceral hypersensitivity (VHS) role at various clinical variants of irritable bowel syndrome (IBS). Material and methods. Overall 120 IBS patients were studied. The age of patients varied from 18 to 52 years (mean 34±11,4 years). The diagnosis is verified by modern instrumental and laboratory diagnostic methods (colonoscopy with biopsy, abdominal ultrasonography etc.), and complied to Rome-III criteria. According to specified criteria, all patients were divided into groups according to prevailing symptoms. Twenty-four patients had constipation predominant IBS, 68 had diarrhea predominant variant of IBS, 28 had unclassified IBS variant. All patients underwent investigation of the background and stimulated colonic motility. The motor function of the colon was studied by solid-state catheter manometry method. The balloon-dilatation test was applied to studying of VHS. Results. Investigation of the large intestinal contractility has revealed that 118 of 120 patients had various disorders of colonic motor function. Several patterns of motor activity were determined according to the frequency of contractions: hypokinetic, hypokinetic with segmental contractions, proximal to distal regions contraction discoordination, normokinetic and hyperkinetic. Comparative analysis has revealed that in all patient groups hypokinetic type of motor activity prevails (57%) that indicates decrease of background motility of sigmoid, colon and rectum at IBS. Stimulated motility examination revealed also electric activity disorders of the colon as well. Sixty-five patients underwent balloon and dilatation test: in 40 of them (62%) signs of VHS of were found. Conclusions. Basal electrophysiologic signs of motor and evacuatory function disorders at different IBS variants were not revealed. Nevertheless causative relationship between large intestinal motility changes and disease symptoms is possible. Signs of VHS are found in the most of patients that proves an important role of this factor in the origin of IBS symptoms, especially - in constipation predominant variant.

The aim of publication. To present modern concept on etiology and pathogenesis of the peptic ulcer (PUD) to general practitioners, to acquaint them with modern diagnostic methods and main treatment approaches of this disease. Summary. The PUD continues to remain one of the most widespread digestive disease. Despite a tendency to decrease of hospital admission rate of patients with uncomplicated PUD, increase in complicated forms of disease rate is noted that it is related mainly to the growing intake of non-steroidal anti-inflammatory drugs (NSAID). Helicobacter pylori infection has a leading role as PUD ethological factor. None H. pylori-associated gastroduodenal ulcers may be caused by NSAID intake or may develop within the other nosological entities (symptomatic stomach and duodenal ulcers). PUD diagnosis includes obligatory testing for H. pylori infection and carrying out eradication in the case of positive takes. At the present time the first line of antihelicobacter therapy includes standard triple clarithromycin and amoxicillin-based therapy, as well as quadrotherapy with bismuth drugs. The second line eradication therapy includes quadrotherapy with bismuth drugs and triple levofloxacin-based therapy. The third line therapy modes should be chosen after assessment of individual antibiotic sensitivity of H. pylori strains. The efficacy control of antihelicobacter treatment should be carried out not earlier than 4 weeks after the end of eradication. Conclusion. Strict conformance of diagnostic algorithm for this category of patients as well as the eradication therapy protocol allows to decrease considerably the risk of recurrence of PUD and its complications.

Aim of the article. To present the technique of twentyfour hour esophageal and stomach pH-metry, indications and contraindications to the study, interpretation o intraesophageal and intragastric pH-metry parameters. Summary. Disorders of the stomach secretory function are one of the factors promoting development of many acid-related diseases such as gastric and duodenal erosions and ulcers, functional dyspepsia (epigastric pain syndrome), gastroesophageal reflux disease. Considering prevalence of these diseases and presence of severe complications, it is necessary to implement up-to-date diagnostic procedures in medical practice. Considerable diagnostic potential of pH-metry allow to verification of disease, individual estimation of the drug efficacy and treatment mode, control of response to carried out treatment, diagnostics of treatment resistance, detection of night «acid breakthrough» episodes and duodenogastric refluxes. Conclusion. 24-hour pH-metry is a fundamental diagnostic method for acid-related diseases. Measurement of gastric acidity and refluxate properties allows to individualize the carried-out therapy that is the most effective approach in treatment of patients.

Aim of investigation. Nowadays the question, whether pegylated interferon should be completely abandoned in the treatment of chronic hepatitis C (CHC) is still open. Beneficial interferon properties include: absence of mutagenic capacity for hepatitis C virus and drug interaction, stimulation of host immune response. These qualities formed the basis for development of the Russian pegilated interferon-alpha 2b (Pegaltevir®, LLC «FARMAPARK», Russia) and carrying out doublestaged randomized open clinical trial: study of safety, tolerability and pharmacokinetics of Pegaltevir® at single injection of increasing doses in various groups of healthy volunteers - the I stage; studying of efficacy and safety of Pegaltevir® in comparison to PegIntron® (Schering-Plough, USA) at CHC as a part of double antiviral therapy with ribavirin (Rebetol®, Schering-Plough, USA) - the II stage. This article presents results of the II phase of investigation. Material and methods. Original study included 140 adult antiviral treatment-naive patients with CHC and compensated liver function. Patients (aged 18 to 70 years) were distributed into four groups. Group 1 (main group, Pegaltevir®/Rebetol® treatment) - 55 patients, HCV genotype 1; group 2 (comparison group, PegIntron®/Rebetol® treatment) - 20 patients, HCV genotype 1; group 3 (main group, Pegaltevir®/Rebetol® treatment) - 47 patients, non-genotype 1 (2 and 3); group 4 (comparison group, PegIntron®/ Rebetol ® treatment) with non-genotype 1 (2 and 3). Assessment of Pegaltevir® efficacy was carried out in 4 weeks (rapid virologic response, RVR) and 12 weeks of treatment (early virologic response, EVR) in groups 1 and 3 in comparison to corresponding scores in groups 2 and 4 (primary criteria of efficacy were estimated in all 140 patients enrolled in original study. The response rate at the moment of secession of antiviral therapy, the sustained virologic response (SVR), histologic response (comparison of paired liver biopsies) served as secondary efficacy criteria and were estimated in 129 patients who completed treatment. The safety analysis was carried out for each patients included in the protocol who received at least one Pegaltevir® dose in comparison to patients who received at least one dose of PegIntron®, - respectively 102 and 38 patients. Results. RVR was comparable in the Pegaltevir® and PegIntron® groups: 65,6 and 82,4% respectively (p>0,05). RVR frequency genotype one patients was 45,3% in Pegaltevir® treatment group and 66,7% in PegIntron® treatment group (p>0,1). At patients with non-genotype 1 (2 and 3): 92,5 and 100% respectively (p>0,05). RVO did not significantly differ in the studied groups: 91,6 and 97,1% for all genotypes respectively (р>0,1). RVO rate for genotype 1 patients in Pegaltevir® group was 86,8%, in PegIntron® treatment group - 94,4% (р>0,1), in non-genotype 1 patients (2 and 3) it reached 97,6 and 100% in the specified patient groups (р>0,1). Response rate at the moment of treatment secession for Pegaltevir® and PegIntron® was 87,4 and 97,1% respectively for all genotypes (р>0,05). In patients with HCV genotype 1 this score Pegaltevir® treatment group reached 79,3%, in PegIntron® group - 94,4% (р> 0,05), in non-genotype 1 patients (2 and 3) - 97,6 and 100% respectively (р>0,1). SVR rate at Pegaltevir® treatment was 82,1% (for all genotypes), PegIntron® - 82,4% (for all genotypes, p>0,1). In HCV genotype 1 patients in Pegaltevir® treatment group SVR made 73,6%, in PegIntron® treatment group - 83,3%, p>0,1, for non-genotype 1 (2 and 3) - 92,9 and 81,3%, p>0,1. No significant differences between basic and control groups at analysis of paired liver biopsies for fibrosis stage reduction rate, absence of negative changes for fibrosis severity and proportion of patients with fibrosis progression were found. Pegaltevir® and PegIntron® treatment groups were comparable safety profile, adverse events were expected, mainly of mild and moderate severity. Conclusion. The hypothesis of identical efficacy of the Russian drug Pegaltevir® tested in the protocol in comparison to PegIntron® was correct and proved. Safety of Pegaltevir® was comparable to safety of PegIntron® as well.

Aim of review. To present literature data on administration of vedolizumab at inflammatory bowel diseases. Summary. The vedolizumab is anti-α4β7-integrin humanized class IgG1 antibodies which suppresses migration of leukocytes in intestinal tissue, interfering thereby with development of pathologic inflammation. GEMINI-1 study of ulcerative colitis has demonstrated efficacy of the drug in remission induction (clinical response rate of 47,1% of patients, clinical remission of 16,9% and endoscopic remission of 40,9% at the 6th week) and in remission maintenance (percent of patients in clinical remission at 52nd week at drug injection every 4 weeks - 44,8%). Similar efficacy was demonstrated for Crohn's disease (GEMINI-2) study in remission induction (clinical response rate - 31,4% of patients, clinical remission - 14,5%) and remission maintenance (percentage of patient in clinical remission by 52nd week at injection of the drug every 4 weeks - 39%). The results received in clinical trials were confirmed by clinical data in the different countries. Safety profile investigations demonstrated low system immune suppression due to specific action mechanism of the drug. Besides, due to α4β7 integrin heterodimer selectivity of vedolizumab, it provides selective block of intestinal leukocyte migration, without affection of central nervous system therefore the risk of the progressing multifocal leukoencephalopathy is not established. Conclusion. Present clinical trials has demonstrated that vedolizumab is effective and safe in treatment of inflammatory bowel diseases.

Aim of review. To present major extraintestinal manifestations of inflammatory bowel diseases (IBD) and basic approaches to management of patients with ulcerative colitis and Crohn's disease having arthropathies and arthrites as extraintestinal manifestations. Summary. Ulcerative colitis and Crohn's disease represent the group of the diseases with unknown etiology encompassed by the term «inflammatory bowel diseases». IBDs are diseases with high social impact due to predominance of young patients of working-age and tendency to chronization of pathological process that leads to deterioration of life of patients and high demand in hospital stay. Ulcerative colitis and Crohn's disease have diverse clinical presentation with various intestinal complications and extraintestinal manifestations. The results of original studies corresponding to world literary data and data of the First European evidencebased consensus on extra-intestinal manifestations in inflammatory bowel disease are presented in this article. Presented data indicates severity and aggressive course of the IBD-associated arthropathies, their contribution to quality of life deterioration and risk of disability that requires diagnostics, timely and adequate pharmacological treatment with multidisciplinary approach. Resolution of this issue is not only an actual trend, but a demand of worldwide medical community for treatment and rehabilitation IBD patients as well. Conclusion. Meditate analysis of extraintestinal IBD manifestations, in particular IBD-associated arthropathy and arthritis, expands potential of time the diagnosis and adequate drug treatment to decrease disability risk and to improve quality of life of IBD patients.

Aim of investigation. To study noninvasive activity markers of inflammatory bowel diseases (IBD) and to estimate correlation between various diagnostic methods for an assessment of clinical and endoscopical activity of ulcerative colitis (UC) and Crohn's disease (CD). Material and methods. Original study included 67 patients with UC and CD in whom clinical and endoscopic activity of the disease with assessed by histological investigation of biopsy specimens. Blood serum cytokines: IL-4, IL-8, tumor necrosis factor α (TNF-α) and fecal calcium binding protein (calprotectin) were assessed. Results. Fecal calprotectin and TNF-α levels were much higher in patients with high disease activity and extent of inflammatory process. Spearman correlation coefficient between endoscopic features and fecal calprotectin (0,82) was higher in the UC patients, than between endoscopic parameters and TNF-α (0,78) in CD patients. Conclusions. Noninvasive inflammatory activity markers should be taken into account and decision-making on diagnostic and treatment strategy, as well as to decrease expensive and invasive diagnostic procedures.

Aim of investigation. To study the effect of maintenance therapy on clinical outcomes of Crohn’s disease (CD) in patients with inflammatory and complicated forms. Material and methods. Five-year prospective study of 210 patients with CD receiving maintenance therapy was carried out. Treatment response was estimated in real-life conditions according to the guidelines of European Crohn's and Colitis Organisation (ECCO). Treatment response and failure at different types of pharmaceutical treatment were estimated. Results. At mesalazine maintenance therapy in patients with inflammatory forms of CD there was no statistically significant demand in treatment enhancement for medium-term perspective (р=0,0088, OR=0,46, 95% CI=0,26-0,80). «The steroid-sparing effect» of immunosuppressors was observed generally in all patients with inflammatory form of disease, which provided reduction of steroid dependency rate by 17%. Repeated prescription of systemic steroids led to development ofsteroid-dependency in complicated forms more frequently (p=0,0083, OR=10,1, 95% CI=1,9-52,5). The long-term outcomes related to biological maintenance therapy demonstrate more frequent mucosal healing at inflammatory (p=0,0423, OR=3,3, 95%CI=1,2-9,4), though not for complicated forms of disease. Conclusions. Mesalazine maintenance therapy is possible only at patients with the inflammatory form of CD without systemic activity under close follow-up by physician. In order to avoid disease progression it is necessary to avoid repeated application of systemic steroids at uncomplicated forms of disease. In complicated cases the combination of systemic steroids and immunosuppressants is ineffective. Biological therapy should be considered as disease-modifying treatment in patients with inflammatory forms of CD. The decision on pharmaceutical treatment of patients with complications should be made by gastroenterologists in consort with surgeons-coloproctologists.

Aim of review. To present data on integration of nutritional pattern and intestinal microbiom spectrum, to estimate the role of each of the listed factors in development of irritable bowel syndrome (IBS) symp­ toms. Summary. In spite of the fact, that IBS is one of the most common gastrointestinal functional disease, etiol­ ogy of disease is substantially unknown. Among factors which promote IBS development specific features of the patient and environmental factors, first of all nutritional stereotype and dietary pattern are considered nowa­ days. These in turn exert direct impact on quantitative and qualitative spectrum of gastrointestinal microbiota which changes, as it was demonstrated in the recent original studies, is an integral part of IBS pathogenesis and is the cornerstone of symptom origin of this func­ tional disorder. Conclusion. Pattern of intestinal microbiome, nutrition­ al stereotype and dietary pattern should be taken into account at management of IBS and planning of clinical or pilot studies in this area.

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.