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Autoimmune hepatitis is a chronic, immune-mediated liver disease characterized by an increased level of immunoglobulins G and/or gamma globulins, the presence of autoantibodies and a typical histological picture. Diagnosis of autoimmune hepatitis causes difficulties due to various variants of the course, wide variability of the clinical picture, which leads to a large number of missed cases of the disease. Treatment of аutoimmune hepatitis is aimed at reducing the activity of an inadequate response of the immune system against cells of its own body and achieving complete remission of the disease. The timeliness of starting treatment is directly related to the prognosis of the disease. These features of the disease necessitate proper patient routing and shortening their path to specialists with knowledge and experience in managing this category of patients.

Background and Aims: Tofacitinib (TFB) appears to be effective in the treatment of ulcerative colitis (UC); however, available real-world studies are limited by cohort size. TFB could be an option in the treatment of acute severe ulcerative colitis (ASUC). We aimed to investigate efficacy and safety of TFB in moderate-to-severe colitis and ASUC., Methods: This retrospective, international cohort study enrolling UC patients with ≥6-week follow-up period was conducted from February 1 to July 31, 2022. Indications were categorized as ASUC and chronic activity (CA). Baseline demographic and clinical data were obtained. Steroid-free remission (SFR), colectomy, and safety data were analyzed., Results: A total of 391 UC patients (median age 38 [interquartile range, 28-47] years; follow-up period 26 [interquartile range, 14-52] weeks) were included. A total of 27.1% received TFB in ASUC. SFR rates were 23.7% (ASUC: 26.0%, CA: 22.8%) at week 12 and 41.1% (ASUC: 34.2%, CA: 43.5%) at week 52. The baseline partial Mayo score (odds ratio [OR], 0.850; P = .006) was negatively associated with week 12 SFR, while biologic-naïve patients (OR, 2.078; P = .04) more likely achieved week 52 SFR. The colectomy rate at week 52 was higher in ASUC group (17.6% vs 5.7%; P < .001) and decreased with age (OR, 0.94; P = .013). A total of 67 adverse events were reported, and 17.9% resulted in cessation of TFB. One case of thromboembolic event was reported., Conclusions: TFB is effective in both studied indications. TFB treatment resulted in high rates of SFR in the short and long terms. Higher baseline disease activity and previous biological therapies decreased efficacy. No new adverse event signals were found., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

The article describes the historical milestones in the study of Crohn's disease from the time of its original description in the 17th century, the revolution in the medical community after the landmark paper in 1932, to the present day. The history of Crohn's disease testifies to the discoveries of the past years, which open up to us the advantages of a scientific approach to the diagnosis and treatment of this disease.

The article describes the main achievements in the study of Crohn's disease, first described as a disease of the terminal ileum, affecting mainly young people, characterized by subacute or chronic necrotizing and scarring inflammation. In subsequent years, the inflammatory disease was also detected in other parts of the gastrointestinal tract. This disease affects the entire intestine and can involve every part of the gastrointestinal tract, from the mouth to the anus. The history of the study of Crohn's disease for 90 years has made it possible to delve deeply into the pathogenesis of inflammation, but has not yet come closer to revealing its etiology. Therefore, it is impossible to talk about the possibility of recovery from CD.

The purpose of the work is to identify the most optimal ways to solve the problem of home parenteral nutrition for patients with short bowel syndrome.Basics. Discussion of the current situation will help optimize the work of the Orphan Diseases Center, lead to a greater introduction of online technology, and aim at the search and implementation of new methods of treating patients in this category.Conclusion. The most optimal strategy has been proposed to improve the interaction between various specialists and patients in need of long-term parenteral nutrition.

Background: Inflammatory bowel diseases (IBD) are characterized by chronic immune inflammation of the mucous membrane and/or the thickness of the intestinal wall, and are also accompanied by disorders of the blood clotting system and the development of a hypercoagulation state., Aim: To identify the frequency of thromboembolic complications (TEC) in IBD patients and to determine the influence of acquired and inherited hypercoagulation factors that contribute to the development of TEС., Materials and Methods: The clinical status of 1,238 IBD patients who were treated in 2019 was evaluated. Of these, 748 patients with ulcerative colitis (UC) and 490 patients with Crohn's disease (CD). Among UC patients, there were 369 (49.3%) men and 379 (50.7%) women. In 10.1% of patients with UC, there were clinically significant feasibility studies. There were 227 (46.3%) men and 263 (53.7%) women among patients with CD; 7.3% of patients with CD had clinically significant feasibility studies., Results: In general 112 (9.0%) of 1,238 IBD patients had clinically significant feasibility studies. Among patients with UC (n=748), 76 (10.2%) showed clinically significant feasibility studies. Among patients with CD (n=490), 36 (7.3%) had a feasibility study. Of 112 IBD patients with clinically significant TEC, 45 (40.2%) had genetic polymorphisms that increase affinity for fibrinogen, increase platelet aggregation, and contribute to a decrease in the activity of folate cycle enzymes, including methylenetetrahydrofolate reductase, which may be manifested by a moderate increase in homocysteine levels. Of the 45 IBD patients with clinically significant TEC due to inherited factors, 30 (66.6%) patients had UC, 15 (33.7%) patients had CD (hazard ratio 1.038, 95% confidence interval 0.7461.444; 2=0.049; p=0.83921); 67 (59.8%) patients with IBD who had clinically significant TEC did not have genetic polymorphisms leading to hypercoagulation., Conclusion: Based on the analysis, we can conclude that such risk factors for the development of TEC as the status of a smoker, long bed rest, taking hormonal contraceptives, varicose veins of the lower extremities, high activity of the disease, glucocorticoids therapy, the extent of intestinal damage in patients with IBD, genetic factors, should be taken into account by gastroenterologists in the treatment of patients with UC and CD. The hereditary factor of hypercoagulation equally affects the development of TEC, both in patients with UC and CD.

Aim: To determine factors of adherence to treatment in patients with ulcerative colitis (UC)., Materials and Methods: The study was performed in the department of treatment of inflammatory bowel diseases in Loginov Moscow Clinical Scientific Center from 2019 till 2021 years by surveying 1089 patients with UC. This analysis revealed patients with high adherence (HAP) and low adherence to treatment (LAP)., Results: In the survey analysis was determined, that there were more low-adherence patients, than high-adherence patients [596 (59.6%) and 404 (40.4%), respectively, (p0.001)]. In the group of HAP (100%) were 297 women (73.5%) and 107 (26.5%) men (p0.001). Also in this group prevailed patients with duration of disease more 5 years 305 (75.5%) and extraintestinal manifestations 261 (64.6%); p0.001. In the group of LAP (100%) were more patients younger 44 years, with bad habits and who did not follow diet (p0.001). The rate of UC reccurence more than 1 time per year was higher in LAP group 430 (72.1%), versus 137 (33.9%) patients in HAP (p0.001). The frequency of surgical procedures in UC patients was significantly higher in LAP 12 (2.0%) in comparison with 2 (0.5%) in HAP group (p0.001)., Conclusion: In our study was determined, that among UC patients, examined in the department of inflammatory bowel diseases, 60% patients had low adherence to treatment. High adherence to the treatment is statistically significantly associated with female gender, family accommodation, non-working patients, extraintestinal manifestations, additional medical maintenance. Low adherence to the treatment is associated with steroids, male gender, age less than 44 year, bad habits (smoking, alcohol consumption), higher education, complicated UC and frequency of reccurences.

The article describes the main historical milestones in the description and study of ulcerative colitis from the time of Hippocrates to the present day. The first description of the morphological picture of non-specific ulcerative colitis (NUC) was presented by the Viennese pathologist Karl Rokitansky in 1842. The term "ulcerative colitis" was coined by S. Wilks in 1859. A detailed description of the disease was presented in 1875 by S. Wilks and W. Maxon. In an independent nosological form, NUC was isolated in 1888 by the English doctor White. Boas in 1903. For the first time, he presented the differential diagnosis of NUC and chronic dysentery. The term "non-specific ulcerative colitis" in Russia was first introduced by A.S. Kazachenko in a report at the XIII Congress of Russian Surgeons in 1913.

Aim: To conduct comparative analysis of histological remission in patients with moderate and severe ulcerative colitis (UC), receiving biological therapy vedolizumab, mesenchymal stem cell (MSC) treatment and combined stem cells and vedolizumab therapy., Materials and Methods: We studied biopsies of 75 patients with total or left-sided moderate and severe ulcerative colitis, divided into groups depending on treatment. The first group of UC patients (n=29) received stem cell therapy 2 mln per kg; the second group of UC patients (n=27) received vedolizumab and the third group (n=19) MSC and vedolizumab. The efficacy of treatment was assessed by C reactive protein (CRP), Mayo score (MS), fecal calprotectin (FC) and Geboes score (GS)., Results: We determined medium correlation between basic FC and MS before treatment (r=0.6605, p0.05). After 12 weeks of treatment in the first group of UC patients (n=29) CRP was 7.82.1 mg/l, FC 409.344.85 g/g, medium GS 1.20.1 points. After 12 weeks of treatment in the second group of UC patients (n=27) CRP was 8.41.4 mg/l, FC 435.547.3 g/g, medium GS 1.350.15 points. After 12 weeks of treatment in the third group of UC patients (n=19) CRP was 6.41.1 mg/l, FC 290.617.5 g/g, medium GS 0.90.1 points. We proved strong direct relationship between FC and GS after 12 weeks of treatment in UC patients, receiving MSC (r=0.8392, p0.05). The statistically significant majority of patients, achieved histological remission, have less than 5-year duration of disease., Conclusion: Our study showed that clinical and endoscopic remission in UC patients does not always correlate with histological remission. Combined anti-cytokine and stem cells therapy contributes to achieve deep remission and decrease mucosa inflammation rather than single MSC or vedolizumab treatment. Deep remission could be achieved by earlier start of biological therapy. FC could be a predictor and marker of mucosa healing and histological remission.

Current conception of deep remission in patients with ulcerative colitis (UC) consists of clinical remission, endoscopic mucosal healing and normalization of laboratory markers. Histological remission should not be used as a primary end point for therapeutic efficacy, but instead should be considered as a marker of deep remission. The main goal of UC treatment should be focused on endoscopic healing of colon mucosa, decrease of inflammation activity, prolonged remission, absence of disease recurrence, and also histologic remission. Nevertheless, the term histologic remission has not yet been fully validated and no histologic indexes have been standardized. We need single unified definition for remission, based on multicentral studies analysis. One of important challenge is restoration of normal colon mucosal and results of multiple studies showed contradictory tests for assessing histologic remission, thus remaining an issue for further discussion.

Aim: To define the frequency of adverse events and loss of the response in patients with ulcerative colitis (UC) and Crohn’s disease (CD), treated with original medicine infliximab (IFX) “Remicaide” and its biosimilars., Materials and Methods: We included 154 patients with IBD: 78 UC patients (50.6%) и 76 CD patients (49.4%), treated with original medicine IFX Remicade and its biosimilars. In our study we did not include patients, who previously underwent induction treatment with IFX and its biosimilar., Results: Among 78 UC patients, IFX was cancelled in 25 (32.0%) patients and they were switched to the other anti-TNF inhibitor or medicine with the another mechanism of action; in patients group, treated with biosimilar – 16 (20.5%) and 9 (11.5%) patients, who were interchanged biosimilar and/or original IFX. Among 76 CD patients IFX was cancelled in 20 (26.3%) patients: 11 (14.5%) patients in group, treated with similar trade name biosimilar, 8 (10.5%) patients, who were interchanged biosimilar and/or original IFX and 1 patient (1,3%), receiving original IFX. We found no difference in the secondary loss of response and adverse events in patients with CD and UC, switched from original IFX to biosimilar (p=0.6257 and p=0.6635, correspondingly). The frequency of the secondary loss of response or adverse events in patients with UC and CD, switched from original IFX to IFX biosimilar, was similar (p>0.05)., Conclusion: Approximately 30% of IBD patients, receiving IFX biosimilar, will be switched to the other anti-TNF therapy or medicine with the another mechanism of action because of secondary loss of response or adverse events., (Consilium Medicum)

Aim: to estimate the quality and availability of medical care for patients with ulcerative colitis (UC) and Crohn's disease (CD), to assess the impact of the economic burden of these diseases on the healthcare budget of Russia and to systematize the main problems in the organization of medical care and drug supply for patients with inflammatory bowel diseases (IBD). Regional IBD databases (2016-2018), official statistical databases, costs of treatment and results of expert interviews with specialists in IBD were used in the study. The analyzed databases showed 104,668 patients with UC in Russia in 2018 (prevalence rate 71 per 100,000 people) and 66,647 patients with CD (prevalence rate of 45 per 100,000 people). The economic burden including agents for biologic therapy (ABT) for the UC was 39.54 billion rubles a year (495 rubles per capita), and CD - 32.98 billion rubles a year (378 rubles per capita). It requires an additional 9.87 billion rubles annually for UC and 9.20 billion rubles annually for CD patients to provide the complete supply with ABT. The annual burden of IBD is 72.52 billion rubles, which is comparable to the costs of other socially significant diseases, including malignant tumors. It shows the high social and economic value of IBD for the country. The main problems of medical care and drug supply for IBD patients are the mismatch of official statistical data and real IBD prevalence in Russia due to absence of comprehensive register and the insufficient supply with ABT due to limited funding. A federal center for IBD should be founded for better quality of registration, for the precise monitoring and for the active management of personal drug supply.

The article is devoted to the current data regarding the pathogenesis, classification and frequency of extraintestinal manifestations (EIMs) in inflammatory bowel diseases. We discuss two distinct theories of EIMs pathogenesis. First, EIMs arise from an extension of antigen-specific immune responses from the intestine to non-intestinal sites. Second, EIMs are independent inflammatory events initiated or perpetuated by the presence of IBD or by shared genetic or environmental risk factors in the host. These mechanisms are not mutually exclusive and may contribute to varying degrees in different EIMs. Early diagnosis of EIMs contributes to prevention disability and enhancement of quality of life of IBD patients. It is concluded that treatment of extraintestinal manifestations should be carried out taking into account the course of the IBD and the multidisciplinary approach, which requires close cooperation of doctors of various specialties. Assessment of prognostic markers and predictors for EIM in IBD will be part of a future investigation.

Rebamipide is a cytoprotector developed in Japan where it has been successfully used for the treatment of stomach diseases for 30 years. Initially discovered effects of the drug included the induction of prostaglandins and the elimination of free oxygen radicals. Recent studies discovered new therapeutic targets of the drug, its new forms that made possible using rebamipid for the treatment of such diseases as NSAID enteropathy, ulcerative colitis, radiation colitis, pouchitis, enteropathy with impaired membrane digestion. It is used in endoscopy, ophthalmology, chemotherapy, rheumatology. The aim of this review is to present current information about the pharmacological and clinical feature of rebamipide and to study its therapeutic potential.

Real - life data on the effectiveness and safety of biosimilar and biologic drugs licensed for treatment of inflammatory bowel diseases (IBD) is lacking., Aim: To investigate efficacy of original Infliximab (IFX) and its biosimilar in treating patients with ulcerative colitis (UC) and determine the frequency of adverse events during 1 year follow - up period., Materials and Methods: Our cohort consisted of 98 ulcerative colitis patients, treated with original IFX and its biosimilar since December 2017 till December 2018 years. Original Infliximab was prescribed in 56 UC patients (57.1%) during 5 years and longer; 16 patients (16.3%) were switched to IFX biosimilar; 13 UC bio - naïve patients (13.3%) received original IFX, 29 (29.6%) patients - biosimilar IFX. In 14 patients (14.3%) original infliximab was rotated with biosimilar. We picked out 42 patients to assess efficacy of original IFX and biosimilar., Results and Discussion: Twelve patients, received original IFX and 28 patients, treated with its biosimilar, showed significant clinical improvement by decreasing Mayo index from 9.7±0.4 and 10.2±0.2 points to 1.9±0.09 and 2.1±0.1 points, accordingly. Also we noticed positive change in laboratory markers - CRP decrease from 89.6±8.7 mg/l and 77.5±8.0 mg/l to 6.5±0.8 mg/l and 6.9±0.8 mg/l (p>0.05), albumin increase from 30.1±4.7 g/l and 29.6±3.6 g/l to 34.1±6.3 g/l and 32.8±5.9 g/l (p>0.05), increase of serum iron levels from 6.4±0.5 mcg/l and 7.1±0.65 mcg/l to 14.6±4.4 mcg/l and 15.9±5.1 mcg/l (p>0.05), hemoglobin increase from 104.7±9.8 g/l and 102.2±8.8 g/l till 124±11.3 g/l and 121±10.9 g/l (p>0.05), and fecal calprotectin decrease from 1680±134 mcg/g and 1720±126 mcg/g till 245.5±33.4 mcg/g and 230.5±29.8 mcg/g (p>0.05). During 1 year follow - up 12 UC patients, treated with original IFX and its biosimilar, developed adverse events. The majority of adverse events (n=8) were registered in patients, rotating administration of original IFX and its biosimilar., Conclusion: IFX biosimilar is effective as well as original IFX. Frequency of adverse events, occurred in patients, treated with original IFX, was comparable with adverse events frequency in patients, received biosimilar IFX. Frequency of adverse events was significantly higher in UC patients, rotating original IFX and its biosimilar.

Aim: To compare fecal calprotectin (FC) concentration with laboratory and diagnostic methods in patients with inflammatory bowel diseases (IBD)., Materials and Methods: The level of FC was measured in 110 patients with established IBD. Crohn diseases (CD) was diagnosed in 50 patients, ileocolitis - in 38 and terminal ileitis in 12 individuals. Ulcerative colitis (UC) was diagnosed in 60 patients, total colitis in 35, left-side colitis in 21 and 4 patients have proctitis. Laboratory data include measurement of FC, leukocytes, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), fecal occult blood. All patients underwent colonoileoscopy (CIS) at the start of disease flare and after 12 weeks of treatment., Results: We found linear correlation between level of FCP and endoscopic activity of CD, analyzing FCP level and endoscopic activity of CD before (during disease flare) and after 12 weeks treatment (r=0.66, p&lt;0.001). Linear correlation between FCP and SES-CD sustained after 12 weeks of treatment (r=0.77, p&lt;0.001). We revealed correlation between FCP concentration. And CRP level (r=0.59, p&lt;0.05). The linear correlation was detected between FCP and endoscopic activity of UC (r=0.88, p&lt;0.001) before the treatment. After 12 weeks of treatment linear correlation was shown between FCP and Meyo scale (r=0.73, p&lt;0.001). IBD patients with FCP more than 200 mcg/g have high risk of disease reccurence in short-term period of time (HR - 8.33; 95% CI 2.05-33.8; χ2 - 11.85; p&lt;0.001) and (HR - 2.7; 95% CI 1.1-6.6; χ2 - 5.3; p&lt;0.05), accordingly., Conclusion: Increased FCP level indicates poor effectiveness of treatment and high risk of reccurence. The level of FCP correlates strongly with recent laboratory and diagnostic indices of activity and enables to determine patients with high risk of reccurence. Thus, thorough monitoring, including additional procedures, contributes to just-in-time treatment modification.

The article is published based on the results of the Russian Consensus on the diagnosis and treatment of primary sclerosing cholangitis (PSC), discussed at the 44th annual Scientific Session of the CNIIG "Personalized Medicine in the Era of Standards" (March 1, 2018). The aim of the review is to highlight the current issues of classification of diagnosis and treatment of patients with PSC, which causes the greatest interest of specialists. The urgency of the problem is determined by the multivariate nature of the clinical manifestations, by often asymptomatic flow, severe prognosis, complexity of diagnosis and insufficient study of PSC, the natural course of which in some cases can be considered as a function with many variables in terms of the nature and speed of progression with numerous possible clinical outcomes. In addition to progression to portal hypertension, cirrhosis and its complications, PSC can be accompanied by clinical manifestations of obstructive jaundice, bacterial cholangitis, cholangiocarcinoma and colorectal cancer. Magnetic resonance cholangiography is the main method of radial diagnostics of PSC, which allows to obtain an image of bile ducts in an un-invasive way. The use of liver biopsy is best justified when there is a suspicion of small-diameter PSC, autoimmune cross-syndrome PSC-AIG, IgG4-sclerosing cholangitis. Currently, a drug registered to treat primary sclerosing cholangitis which can significantly change the course and prognosis of the disease does not exist. There is no unified view on the effectiveness and usefulness of ursodeoxycholic acid and its dosage in PSC. Early diagnosis and determination of the phenotype of PSC is of clinical importance. It allows to determine the tactics of treatment, detection and prevention of complications.

The review presents data on calprotectin, lactoferrin, leukocytes labeled with isotope indium 111In, calgranulin C and pyruvate kinase type M2 - highly sensitive biomarkers to assess the severity of intestinal inflammation. Their importance in diagnostics, determination of treatment efficiency, including as predictors of recurrence of ulcerative colitis and Crohn's disease is shown.

Aim: To study epidemiology and risk factors for Clostridium infection (CDI) associated with Clostridium difficile in patients with inflammatory bowel disease (IBD)., Materials and Methods: 1179 medical records were analyzed in a retrospective study of patients with IBD, of which 764 patients met the inclusion criteria. Patients were divided into 2 groups based on the presence of a preliminary diagnosis of CDI. Statistical analysis was carried out using Pearson Chi-square and two-sample t-test., Results: The incidence of CDI in patients with IBD was 17.3%, with the same prevalence in patients with Crohn's disease (CD) (n=53/40.1%) and ulcerative colitis (UC) (n=79/59.9%). The mean age of occurrence of CDI in patients with IBD was 37.8±12.9, 84.8% of infections were community-acquired and only 4.5% occurred in medical institutions. Only 21.2% of all patients with CDI had a history of antibiotic use, and 24.2% had previously used steroids. Long-term immunosuppressive therapy in patients with IBD has an impact on the development of CDI: among patients with CDI 45.5% long-term received azathioprine/6-mercaptopurine, in patients without IBD - 17.7% (p&lt;0.001). 18% of patients with CDI had control of the disease with salicylate therapy, while 62% of patients without CDI achieved remission by taking salicylates (p&lt;0.05)., Conclusion: The prevalence of CDI in UC and CD is comparable (p=0.16). The study shows that patients with IBD are more sensitive to the development of CDI at a young age, while not having such traditional risk factors as recent hospitalization or antibiotic use. Patients with IBD with CDI in history often noted the ineffectiveness of therapy with salicylates, often require the assignment of biological therapy. IBD patients with CDI have a lower average albumin, and a higher activity of the inflammatory process.

Aim: To assess the efficacy and tolerance of certolizumab pegol (CP) in patients with Crohn's disease (CD) treated in the Department of inflammatory bowel diseases of the A.S. Loginov Moscow Clinical Research Center and to determine the predictors of response to therapy., Materials and Methods: All patients with CD who had received the treatment of CP were observed prospectively for at least 6 months or until the date of discontinuation of the drug. The effectiveness of the study was assessed response to therapy by the 6th week, maintaining the clinical response (6th and 26th weeks), the dynamics of endoscopic parameters by the 10th and 54th week of therapy, long-term maintenance of remission, healing fistula. Used univariant and multivariate analyses of predictors of response to treatment., Results: The study included 39 patients: 12 (30.7%) men and 27 (69.3%) female, the average duration of observation was 104 weeks. The interdepartmental range was in the range from 28 to 158 weeks. Clinical improvement occurred in 38 out of 39 (97.4 %) patients with CD. Comparative analysis of response to treatment with CP have bionaive patients previously treated with another inhibitor of TNF-α. In the group of bionaive response to therapy in a month, 6 months and at the end of the observation period occurred at 100.0%, 95.0% and 95.0%, respectively. In the group of patients previously treated with GSI, the response rate was about 94.4 %, 88.9 % and 77.7% week 54 endoscopic response and endoscopic remission was maintained in 46,2% and 30,1% patients, complete healing of the mucosa on the background of maintenance therapy, CP, was preserved in 20.5% of patients with Crohn's disease. In the group of patients with perianal lesions (n=13) complete closure of all fistulas was observed in 5 (38.6 %) patients, partial response was observed in 4 patients (30,7%) patients, in 4 (30.7 %) closure of fistulas occurred. The frequency of adverse events was 0 cases (0.0%). The dose escalation was required in 3 patients (7,7%) patients with CD. Dose escalation in our study required patients with high initial CDAI and previous inefficiencies of the other two inhibitors of TNF-α. Reliable predictors of secondary loss of response and need for dose escalation of the drug has been the continued level of CRP &gt;5 mg/l after 2 weeks initiation of therapy CP and smoking., Conclusion: The obtained results demonstrate the efficacy and tolerability profile of CP appropriate for long-term CD therapy in real clinical practice.

Aim: To compare the effectiveness of the effect of combination therapy (local and systemic administration) with bone marrow mesenchymal stromal cells (MSC), anticlitokine therapy with infliximab (IFX), and antibiotic (AB)/immunosuppressive (IS) therapy on the frequency of healing of simple perianal fistulas in Crohn's disease., Materials and Methods: In our study, the 1-st group of patients aged 19 to 58 years (Me-29) (n = 12) received MSCs culture systemically according to the scheme and locally. The 2-nd group of patients with CD (n = 10) from 20 to 68 years old (Me-36) received anticytokine therapy with infliximab (IFX) according to the scheme. The 3-d group of patients with CD (n=14) from 20 to 62 years old (Me-28) received antibiotics (AB) and immunosuppressors (IS). Efficacy was assessed by the index of perianal activity of Crohn's disease (PCDAI) and the frequency of relapses., Results: After 12 weeks among patients of the 1-st group, healing of simple fistulas was noted in 8/12 patients (66.6%), in the 2-nd group in 6/10 (60.0%) In the 3-d group, in 1/14 patients (7.14%). After 6 months in the 1-st group of patients, healing of simple fistulas was preserved in 8/12 (66.6%), in the 2-nd group - in 6/10 (60.0%). In the 3-d group - in 1/14 patients (7.14%). After 12 months in the 1-st group, healing of simple fistulas was preserved in 7/12 (58.3%), in the second group - in 6/10 (60.0%). In the 3-d group - in 2/14 patients (14.3%). After 24 months, among the patients of the 1-st group, fistula closure was maintained in 5/12 patients (41.6%), in the 2-nd group - in 4/10 (40.0%). In the 3-d group - in 0/14 patients (0.0%)., Conclusion: Combined cellular and anticytokine therapy of CD with perianal lesions significantly contributes to the more frequent and prolonged closure of simple fistulas, as compared to antibiotics/immunosuppressors, and to a decrease in the frequency of recurrence of the disease.

Personalized medicine (personalized medicine, individualized medicine) represents the totality of methods of prevention of a pathological condition, diagnosis and treatment in the event of its occurrence, based on individual patient characteristics. Such individual characteristics include genetic, epigenetic, and transcript, proteome, metabolomic and metagenomic markers, as well as a set of variable phenotypic traits - both of the patient's body and its separate tissues or cells. For example, treatment of inflammatory bowel diseases (IBD) can most clearly show the importance of applying personalized approaches. Currently in the treatment of patients with IBD paid great attention to genetic studies, monitoring of the concentration of the biological drugs and the level of antibodies to them, the role of microbiota as a predictor of effectiveness of therapy of IBD. Used clinical, laboratory, instru- mental methods, as well as new biomarkers to assess the forecasting efficiency of conservative therapy in IBD patient. In the future treatment of patients with IBD will include a number of personalized data in order to better predict outcomes of the disease in each patient and more ac- curately select the appropriate treatment regimen.

Aim: To evaluate the effectiveness of MSCs therapy in patients with CD receiving azathioprine (AZA)., Materials and Methods: The study included 34 patients with inflammatory (luminal) form of CD. The 1st group of patients (n=15) received an- ti-inflammatory therapy using MSCs culture in combination with AZA. The 2nd group (n=19) received MSCs without AZA. The severity of the attack was assessed in points in accordance with the of Crohn's disease activity index (CDAI). Immunoglobulins (IgA, IgG, IgM), interleukins (IL) 1β, 4, 10, tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), transforming growth factor-1β (TGF-1β), C-reactive protein (CRP), platelets and erythrocyte sedimentation rate (ESR) at 2, 6 and 12 months from the beginning of MSCs therapy., Results: The initial mean CDAI in the 1st group was 337.6±17.1 points, in the 2nd group - 332.7±11.0 points (p=0.3). In both groups of pa- tients there was a significant decrease in CDAI after 2 months. From the beginning of therapy MSCs: in the 1st group to 118.9±12.4 points, in the 2nd - 120.3±14.1 points (p=0.7), after 6 months - 110.3±11.1 and 114.3±11.8 points (p=0.8), respectively. After 12 months CDAI in the 1st group was 99.9±10.8 points, in the 2nd group it was 100.6±12.1 points (p=0.8). The level of IgA, IgG, IgM was significantly lower in the group of patients with a longer history of the disease and long-term ASA. After the introduction of MSC in both groups of patients with BC, there was a tendency for the growth of pro- and anti-inflammatory cytokines, with a significantly lower level of pro-inflammatory cytokines - INF-γ, TNF-α, IL-1β - in the 1st group, indicating potentiation of the immunosuppressive effect of MSCs and AZA, which provides a more pro- nounced anti-inflammatory effect., Conclusion: Transplantation of MSCs promotes an increase in the serum of patients with CD initially reduced concentration of IG, cytokines and restoring their balance as the onset of clinical remission. The combination with AZA has a more pronounced anti-inflammatory effect.

Aim: To evaluate the efficacy and safety of adalimumab (ADA) in patients with Crohn's disease (CD) treated at the Department of Inflammatory Bowel Diseases, Moscow Clinical Research and Practical Center, and to determine the predictors of a therapy response., Subjects and Methods: All the patients with CD treated with ADA were followed up for at least 6 months or until the drug was discontinued. Therapeutic effectiveness was evaluated at 4 weeks and 6 months after the initiation of treatment and at the end of a follow-up. Complete intestinal mucosal healing was assessed at 3 and 12 months following treatment initiation. Univariate and multivariate analyses were used to determine the predictors of treatment response., Results: A clinical analysis covered 70 patients (57.1% male); the follow-up period averaged 112 weeks. Perianal fistulas were at baseline established in 22 (31.4%) patients with CD. 12 (17.4%) patients had been previously treated with infliximab (INF), 7 of them discontinued the drug for secondary loss of response and 5 for adverse reactions. 68 (97.1%) patients responded to an induction course of ADA. At 4 weeks, 6 months, and at the end of the follow-up, clinical remission occurred in 66.7, 80.4 and 67.4 % of patients with luminal CD and in 45.4, 36.5, and 36.4% of those with perianal CD, respectively. At 3 and 12 months and at the end of the follow-up, there was complete healing of the intestinal mucosa in 23.5, and 41.2 and 29.5% of cases, respectively. Six (8.8%) patients responding to the induction course needed to be optimized with ADA to 40 mg weekly. The time interval between treatment initiation and dose optimization averaged 30 weeks (range 12-120 months). There were 15 (21,4%) adverse events that were responsible for ADA discontinuation in 3 (4,2%) patients., Conclusion: The findings demonstrate the efficacy and safety of ADA used in clinical practice.

Introduction: Recently, more and more attracted the attention of cell therapy, which requires a study of the efficacy and safety of allogeneic MSCs transplantation in acute and chronic inflammatory reactions. The aim of our study was to examine the effectiveness of transplantation of allogeneic mesenchymal bone marrow stromal cells for the healing of surgical wounds the glandular stomach in rats., Material and Methods: Using white Wistar rats. Producing cell transplantation mononuclear fraction derived from rat bone marrow aspirate. Injected cells 8 and 9 th passage. The dose of cells administered to 3-th and / or 7-th days 3,5h106 cells / ml twice or 5,0h106 cells / ml dose. Autopsy on day 10-th and 17-th. The serum ELISA determined the content of the pro- and anti-inflammatory cytokines IL1β, TNFα, IFNy, IL-4., Results and Discussion: Introduction MSCs contributed to the decline of the immune mediators of inflammation IL1P, TNFa, IFNy, increase anti-inflammatory IL4. Quality improved healing., Conclusion: Rapid curative effect of stem cells may be associated with the formation of blood immune cells (macrophages) that produce substances that restore damaged tissue. They restore the balance between Th1 and Th2.

Aim: To compare results of treatment in patients with moderate and severe ulcerative colitis (UC), receiving standart anti-inflammatory therapy (second group) and its combination with bone marrow-derived mesenchymal stromal cells (MSC) (first group)., Results: Complex therapy of UC acute flare-up, including MSC did not influence on reccurence frequency, remission duration and mean value of clinical and endoscopic activity indices during 1 year of follow-up: in 1 group UC flare-up occurred in 2 (16.7%) patients, in 2 group--in 3 patients (30%). RR was 0.3 (95% CI 0/08--1.36; p=0.2; x2=1.47). After 2 years of follow-up risk of UC exacerbation in 1 group was 3 times lower than in the 2 group (p=0.03). Mean duration of remission in the 1 group was 22 months, in the 2 group--17 months (p=0.049). After 3 years of follow-up remission duration in the 1 and 2 groups were 22 and 22 months, respectively (p=0.66). Activity Index according to Rachmilevich in the 1 group was 4.75+/-1.13 points, in the 2--8.1+/-1.1 points (p=0.001)., Conclusion: MSC application increases efficacy of anti-inflammatory treatment in patients with acute exacerbation of UC.

Aim: to retrospectively evaluate the efficiency of long-term infliximab (INF) therapy in patients with refractory ulcerative colitis (UC)., Subjects and Methods: The investigation enrolled 48 patients with refractory UC who had taken IFL in 2008 to 2014. Steroid-dependent or steroid-refractory UC was established in 40 (83.3%) patients; 8 (16.7%) were noted to be refractory to therapy with azathioprine or 6-mercaptopurine. Cytomegalovirus DNA was identified in the biopsy specimens of the large intestinal mucosa (LIM) from 7 patients. One patient received antiviral therapy. Induction therapy with IFL was in its administration in a dose of 5 mg/kg at 0, 2, and 6 weeks, then maintenance therapy was continued every 8 weeks., Results: After an IFL induction cycle, 3 (6.3%) patients were unresponsive to therapy and were excluded from the investigation. At present, 25 (55.5%) of the 45 patients who have responded to the therapy continue to take IFL 5 mg/kg every 8 weeks and are in clinical remission; 4 (8.8%) patients receive intensified IFL therapy. Initially 23 patients received combined therapy with IFL + an immunosuppressive drug; 22 had IFL monotherapy. Escape from the effect of the performed therapy was observed in 5 (11.1%) patients, which required its intensification. The intensified therapy resulted in sustained remission in 4 (8.8%) patients; colectomy was carried out in one (2.2%) case. Secondary loss of response to IFL, its intolerance, development of severe infectious complications, which did not allow for further maintenance therapy with IFL, were seen in 11 (24.4%) patients; 5 (11.1%) stopped the therapy because they had been excluded from the additional drug subsidy list. Maintenance therapy with IFL proved successful during 64 months in 29 (64.4%) of the 45 patients and during 64 months if its intensity, when the occasion required, was enhanced., Conclusion: The long-term use of IFL in UC confirmed its high efficacy in achieving clinical response, in inducing a clinical remission and its capacity to heal LIM, and in sustaining remission.

Aim: To compare the safety of therapy in patients with ulcerative colitis (UC) and Crohn's disease (CD) who have received combination anti-inflammatory therapy using bone marrow mesenchymal stromal cells (MSC) and standard therapy with 5-aminosalicylic acid, glucocorticosteroids, and immunosuppressive agents., Subjects and Methods: Unfavorable consequences were analyzed in 103 patients (56 with UC and 47 with CD) with inflammatory bowel disease (IBD) after MSC administration. The findings were compared with data obtained in 208 patients with UC and CD on standard anti-inflammatory therapy. All the patients were similar in demographic parameters, the duration of disease, the extent of intestinal injury, the nature of a course, the type and degree of disease. The analyzed groups did not include patients who had received therapy with anti-TNF-α drugs. The safety of therapy was evaluated from the presence of complications occurring during the follow-up., Results: By analyzing the unfavorable consequences in 103 patients with IBD and comparing them with treatment results in 208 patients with UC and CD on standard anti-inflammatory therapy, the authors revealed no differences in the development of acute posttransfusion reactions, infectious complications, exacerbations of chronic inflammatory diseases, severe infectious complications, malignant transformation, and fatal cases in patients with UC and CD, except for those with transient fever., Conclusion: The results of this study demonstrate that the innovative method of cell therapy is clinically safe.

Perianal fistulas are the most common and frequently encountered types of fistulas in Crohn's disease (CD). They are incurable, may worsen quality of life in a patient and increase the risk of total bowel resection. Despite the significant impact of biological (anticytokine) therapy for fistular CD, treatment in this category of patients remains a difficult task with the high risk of recurrent CD. Mesenchymal stromal cells (MSCs) having immunomodulatory properties and a great regenerative potential are currently also used to treat fistulas in CD and perianal fistulas of another etiology. The given clinical case demonstrates that complete fistula healing could be achieved only after a few local administrations of MSCs in combination with infliximab and azathioprine. World and our experiences indicate that there is a need for randomized controlled trials with a sufficient number of patients to prove the efficacy of MSCs in the combination therapy of fistulas in CD.

Aim: To define the value of adhesion molecules (sVCAM-1 integrin, P-selectin, E-selectin, and L-selectin) for the prediction and evaluation of the efficiency of treatment in patients with ulcerative colitis (UC) and Crohn's disease., Subjects and Methods: Twenty-six patients with UC and 14 patients with CD were examined. Of them, 16 patients took infliximab (INF) in a dose of 5 mg/kg of body weight according to the standard scheme; 14 patients received cultured mesenchymal stem stromal cells (MSSCs) in a quantity of 150 x 10(8) cells, and 10 had azathioprine (AZA) 2 mg/kg and glucocorticosteroids (GCS) 1 mg/kg of body weight. Enzyme immunoassay was used to determine the serum concentration of the adhesion molecules (L-selectin, E-selectin, P-selectin, and sVCAM-1 integrin) before and 2 months after treatment., Results: The signs of bowel inflammatory disease activity and the elevated levels of adhesion molecules whose synthesis did not occur under normal conditions remained in the patients receiving GCS and AZA. INF treatment caused a decrease in P-selectin, E-selectin, and sVCAM-1 levels to 8.9 +/- 1.0, 5.5 +/- 1.7, and 9.5 +/- 4.4 ng/ml, respectively (p < 0.001). Incorporation of MSSCs was followed by a reduction of the concentrations of P-selectin and E-selectin to 6.9 +/- 1.1 and 5.7 +/- 1.3 ng/ml, respectively (p < 0.001). The level of integrin (cVCAM-1) fell to 12.2 +/- 2.2 ng/ml (p > 0.1); that of L-selectin did not drop after MSSC administration and INF induction therapy., Conclusion: P-selectin, E-selectin, L-selectin, and sVCAM-1 integrin are current inflammatory markers and may be used to evaluate the efficiency of standard and biological therapies for inflammatory bowel diseases and to predict disease course.

We analyzed medium-term efficiency and safety of biological therapy of Crohn's disease, in particular transplantation of allogenic mesenchymal stromal bone marrow cells and anticytokine therapy with selective immunosuppressive agents. It was found that both methods of biological therapy of refractory Crohn's disease resulted in clinical and in some cases endoscopic remission. In most cases, clinical remission was maintained without steroid hormone therapy. Thus, both methods produce comparable clinical results. It was concluded that transplantation of mesenchymal stromal bone marrow cells could be considered as a promising method in the therapy of refractory Crohn's disease comparable by its efficiency with infliximab therapy.

Pancreatitis was modeled before and after preliminary transplantation of stem cells and serotonin. It was demonstrated that transplantation of mesenchymal stem cells and activation of serotoninergic system prevent the development of pancreatitis.

The effects of infliximab, an anticytokine drug, on the course of inflammatory process was studied on the model of ulcerative colitis induced by injection of picrylsulfonic acid. Infliximab prevented the development of toxic dilatation and a drop of bioelectric activity of smooth muscles via maintenance of activity of the intramural nervous system neurons.

Aim: To elaborate optimal cell culture administration regimens to enhance the efficiency of anti-inflammatory therapy for inflammatory bowel diseases., Subjects and Methods: Three groups of patients with chronic continuous or chronic recurrent ulcerative colitis (UC) were formed according to the treatment option: 1) 15 patients with UC, in whom mesenchymal stromal cells (MSC) were thrice administered for a month at a one-week interval; 2) 20 patients with UC who received MSC once; 3) 20 patients with UC who had standard anti-inflammatory therapy with 5-aminosalycilic acid (5-ASA) preparations and glucocorticosteroids (GCS). The clinical activity of UC was evaluated using the Rachmilewitz index; its endoscopic pattern was assessed with the Mayo index. UC histological specimens were scored using the Gebs scale. To ascertain the duration of remission, the authors used the Kaplan-Maier survival curve method and calculated relative risk (RR) and odds ratio with 95% confidence intervals., Results: Following 12 months, allogeneic bone marrow (BM) MSC transplantation performed thrice during a month caused the greatest reduction in the Rachmilewitz clinical activity index, Mayo endoscopic activity index, and Gebs pathohistological index in patients with UC as compared to those who had underwent one transplantation or received 5-ASA preparations and GCS (p < 0.05). The duration of remission also depended on the chosen therapy option for UC and the frequency of cell culture administration: the longer duration was recorded in patients who were infused thrice with allogeneic BM MSC., Conclusion: In the patients who had undergone one MSC administration, the risk of recurrent UC was higher than in those who had received MSC thrice during a month (a 2-year follow-up) and comparable with the RR of recurrent UC in the patient receiving only 5-ASA preparations, GCS, and/or immunosuppressants.

Out of 28 patients with inflammatory bowel disease in 11 (39.3%) revealed the presence of autoantibodies to gastric parietal cells. Appointment of MSC and infliximab did not lead to a reduction in antibody levels, in fact, in 6 (21.4%) patients had a further increase in the content of mentioned autoantibodies. Identification of autoantibodies to gastric parietal cells is considered as adherence to IBD autoimmune gastritis (formation of a systemic process) that requires use of corticosteroids. Transplantation of mesenchymal stromal cells in IBD reduces enhanced circulation of autoantibodies against antigens of neutrophils cytoplasmic structures, thereby reducing the severity of autoimmune reactions. Transplantation of MSCs reduces autoaggression in patients with ulcerative colitis, reducing the autoreactive clone of B lymphocytes (CD19+CD5+). Analysis effectiveness of the therapy. Transplantation of MSCs in IBD has a systemic immunoregulatory effect: on the one hand, stimulates oppressed cytokine synthesis, on the other--reduses the intensity of the autoimmune reactions and activity of pathological processes. Infliximab selectively blocks TNF-alpha, without affecting other proinflammatory cytokines.