[Screening for celiac disease among patients of the gastroenterological profile].

AIM: To determine the frequency of celiac disease (CD) among gastroenterological patients and criteria for its active detection. MATERIALS AND METHODS: 1.358 patients referred for gastroenterologist consultation from 2016 to 2019 was conducted, of which 140 had CD (339 males 24.9%; 1019 females 75.1%). The average age was 40.415.4 (1886 years). All patients were determined anti-TTG IgA, IgG, and analyzed the clinical symptoms and analysis. The results were subjected to statistical processing Statistica 13.3 (StatSoft Inc., USA). RESULTS: In patients without CD (1218 people), high level of anti-TTG IgA and IgG was observed in 59 (4.8%), an increase in anti-TTG IgA in 54 (4.4%), and anti-TTG IgG in 38 patients (3.1%). The CD diagnosis confirmed in 51 patients (4.2%). The main symptoms were diarrhea (88%), abdominal pain (60.7%), bloating (73.8%), nausea (40.3%), weight loss (44.3%). Anemia was determined in 31.6%, serum iron 33%, hypoproteinemia 12.6%, hypoalbuminemia 12%, hypokalemia 5.48%, hypocalcemia 21.9%. An increase in the level of AST 14.5%, ALT 14.6%. Comparative analysis showed that in the group with newly detected CD, anemia, malabsorption syndrome, increase AST, ALT were significantly more frequent than in patients with normal antibodies, which confirms the need to detect CD among patients with these laboratory abnormalities. CONCLUSION: The incidence of CD among patients with a gastroenterological symptoms was 4.2%. Analysis of clinical and laboratory data has shown that a comprehensive analysis of clinical symptoms and laboratory indicators at the stage of primary treatment will allow timely identification of CD patients and prescribe GFD.

[Bile acids are a risk factor for colorectal cancer].

Bile acids were first considered carcinogenic in 1939. Since then, accumulated data have associated colon cell changes with high levels of bile acids as an important risk factor for developing colorectal cancer, which is more common among people who consume large amounts of dietary fat. Secondary bile acids formed under the influence of the intestinal microbiota can cause the formation of reactive forms of oxygen and nitrogen, disruption of the cell membrane, mitochondria, DNA damage, reduction of apoptosis, increased cell mutation, turning them into cancer cells. High-fat diet, intestinal microflora, bile acids are a risk factors for colorectal cancer.

Celiac disease associated with ulcerative colitis.

The article provides clinical observation of a patient who was diagnosed with celiac disease when he was 52 years (Marsh stage IIIB). Following gluten-free diet (GFD) clinical remission and restoration of small intestinal mucosa (SIM) structure occurred, however in 6 years ulcerative colitis developed and an impairment of SIM morphological structure was identified (Marsh stage IIIA). Ulcerative colitis and celiac disease remission is supported by GFD, anti-cytokine therapy (adalimumab) in combination with mesalazine.

Important problems in the diagnosis and treatment of autoimmune hepatitis (based on the Russian consensus 2017).

The analysis of publications devoted to the Russian Consensus on the Diagnostic and Treatment of Autoimmune Hepatitis (AIH), which was considered at the 43rd annual Scientific Session of the CNIIG From Traditions to Innovation (March 4, 2017) is carried out. The presence of clear algorithms and recommendations for the diagnosis and treatment of AIH significantly help the doctor in real clinical practice, but do not exclude a personified approach to the patient.

The role of small intestine in pathogenesis of common variable immune deficiency.

AbstractThe article presents the results of examination of 32 patients with common variable immune deficiency (barn) with involvement in the patho- logical process of the digestive system. The features of the clinical picture, the content of immunoglobulins in the blood serum, morphological structure of the mucosa and small intestine as well as treatment. Special attention is paid to the small intestine in the pathogenesis of the barn.

Mesenchymal stromal cells of bone marrow and azathioprine in Crohn's disease therapy.

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) 1ß, 4, 10, tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), transforming growth factor-1ß (TGF-1ß), 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-1ß - 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.

Is it necessary to use capsular endoscopy to diagnose celiac disease?

AIM: To clarify the indications for capsular endoscopy (CE) in patients with celiac disease. MATERIALS AND METHODS: The study included 10 patients with celiac disease (6 women, 4 men) aged 22 to 69 years. The median age was 42.4±17.5 years. The diagnosis of celiac disease established on the basis of histological examination of the mucous membrane (MM) of the duodenum and detection of antibodies to diaminononane peptide gliadin and to tissue transglutaminase. In three patients celiac disease was diagnosed for the first time, in others - in terms of 3 months to 2 years. CE was performed using a Given Imaging systems (Yokneam, Israel), Olympus (Japan), the obtained data were analyzed using Rapidr® Reade (version 7.0). The results of the endoscopy were compared with the data of 78 patients examined by us, in which the indicators conformed to the normal CE criteria. RESULTS: All patients with celiac disease showed characteristic endoscopic markers of atrophy from the small intestine: scallop, nodularity, decrease in height and number of folds. Paid attention to the mosaic of defeat in the form of "atrophy fields" against a background of slightly modified MM. Erosive-ulcerative lesions of the small intestine were found in 4 patients. CONCLUSION: Indications for the appointment of CE in patients with celiac disease is the lack of response to treatment, which is based on strict adherence to gluten-free diet, the assumption of erosive and ulcerative lesions MM of the small intestine and refractory form of the disease. CE makes it possible to establish the extent of atrophy from the small intestine, which allows you to use it to evaluate the effectiveness of treatment.

[All-Russian Consensus on Diagnosis and Treatment of Celiac Disease in Children and Adults]. / Vserossiiskii konsensus po diagnostike i lecheniyu tseliakii u detei i vzroslykh.

The paper presents the All-Russian consensus on the diagnosis and treatment of celiac disease in children and adults, which has been elaborated by leading experts, such as gastroenterologists and pediatricians of Russia on the basis of the existing Russian and international guidelines. The consensus approved at the 42nd Annual Scientific Session of the Central Research Institute of Gastroenterology on Principles of Evidence-Based Medicine into Clinical Practice (March 2-3, 2016). The consensus is intended for practitioners engaged in the management and treatment of patients with celiac disease. Evidence for the main provisions of the consensus was sought in electronic databases. In making recommendations, the main source was the publications included in the Cochrane Library, EMBASE, MEDLINE, and PubMed. The search depth was 10 years. Recommendations in the preliminary version were reviewed by independent experts. Voting was done by the Delphic polling system.

[Celiac disease detection rate in gastroenterological patients].

AIM: To determine celiac disease detection rate in patients with digestive disease. SUBJECTS AND METHODS: A total of 318 gastroenterological patients admitted to be treated at the Central Research Institute of Gastroenterology in September to October 2012 were examined. The patients' age was 18 to 74 years (mean 51.5±16.4 years). Immunoglobulin A (IgA) and immunoglobulin G (IgG) anti-gliadin antibodies (AGA), IgA anti-tissue transglutaminase (anti-tTG) antibodies and IgG anti-tTG antibodies were determined. When the antibodies were elevated, esophagogastroduodenoscopy with duodenal biopsy was performed. RESULTS: Forty-one of the 318 patients were found to have higher AGA (12.9%); out of them IgA AGA were in 17 (5.35%) patients and IgG AGA were also in 17 (5.35%). Elevated levels of both antibodies (IgA AGA and IgG AGA) were seen in 7 (2.2%) patients. Overall, the detection rate of increased AGA levels was 12.9%. The antibodies were more commonly higher in patients with liver diseases (21.8%) and in those with inflammatory bowel diseases (21.6%). Both IgA anti-tTG, IgG anti-tTG and IgA AGA, IgG AGA were detected in 6 (1.9%) of the 318 patients. The diagnosis of celiac disease was verified by duodenal histological examination in 3 (0.94%) of the 318 patients. CONCLUSION: The celiac disease detection rate in gastroenterological patients was 0.94%.

[Seronegative celiac disease: A case report].

The paper describes a rare case of celiac disease in the absence of serum anti-tissue transglutaminase (anti-tTG) antibodies. A 51-year-old patient has been suffering from diarrheas for 20 years. He has lost 15 kg gradually; weakness progressed; muscle cramps, leg edemas, and signs of dynamic pseudoobstruction appeared. Morphological examination revealed small intestinal mucosal (SIM) villous atrophy (Marsh IIIC stage). IgA anti-tTG and IgG anti-tTG antibodies were 0.086 and 0.178, respectively. The patient was prescribed a gluten-free diet, water electrolyte solutions to correct metabolic disturbances, and prednisolone. During a control examination after 6 months, the patient had no complaints and gained 22 kg, and the SIM villus height was increased. The specific feature of the case is specific negative serological tests for celiac disease.

[Carbohydrase activities may serve as a marker for small intestinal mucosal recovery in patients with celiac disease].

Aim. To clinically evaluate the activity of glucoamylase, maltase, saccharase, and lactase in the small intestinal mucosa (SIM) of patients with celiac disease. Subjects and methods. Twenty-nine patents with celiac disease were examined. The disease was first detected in 8 patients; in the remaining patients, it had been diagnosed 6 months to 35 years before. The diagnosis was verified by histological examinations of duodenal biopsy specimens and by determination of immunoglobulin (Ig) A and G antibodies to tissue transglutaminase (atTG) and gliadin (AGA) by an enzyme-linked immunosorbent assay (ELISA). Carbohydrase activities were estimated in the duodenal biopsy specimens, by applying the method of A. Dahlquist. Results. In the control group, the activities of glucoamylase, maltase, saccharase, and lactase averaged 598.8+184.2, 825.3+239.3, 180.2-68.1, and 53.4+16.3 ng/glucose/mg tissue min, respectively. In the patients with celiac disease, the average activities of all the examined enteric enzymes were significantly below the normal value even they had been on a gluten-free diet (GFD) for 10 years or longer. Complete SIM structural recovery (Marsh stage 0) occurred in only 7 of 18 patients who had been on a strictly GFD. Serological (atTG and AGA) tests got also negative in all the 7 patients with completely recovered SIM. Six of the latter patients continued to have abdominal bloating and borborygmus, unstable stool with a propensity for diarrhea and weakness. Each was detected to have a lower activity of one or a few enzymes. The activity of all the carbohydrases reached its normal value in only 1 patient and she felt healthy, without perceiving any food intolerance. Conclusion. The activity of membrane enzymes may serve as a marker for the degree of SIM recovery in patients with celiac disease.

[Significance of a method for determination of deamidated gliadin peptide in the diagnosis of celiac disease].

AIM: To define the value of a new enzyme immunoassay in determining the level of anti-deamidated gliadin peptide (DGP) antibodies (Abs) in the diagnosis of celiac disease. SUBJECTS AND METHODS: One hundred and twenty-four patients treated at the Department of Intestinal Pathology, Central Research Institute of Gastroenterology, were examined. Enzyme-linked immunosorbent assay (ELISA) was employed to determine Abs to tissue transglutaminase (tTG) and DGP of the IgA and IgG classes in the sera of all the patients. The diagnosis of celiac disease was verified by the histological examination of small bowel mucosa biopsy specimens. RESULTS: The examinees were divided into 3 groups: 1) 27 patients first diagnosed with celiac disease; 2) 40 patients keeping a gluten-free diet (GFD); 3) 57 patients with other gastrointestinal diseases (a comparison group). In the patients first diagnosed with celiac disease, the detection rate of elevated titers of anti-tTG and anti-DGP Abs in the IgA class was equal and constituted 92.5%; that in the IgG class was 96.2 and 55.5%, respectively. The comparison group showed an increase in the DGP levels in the IgA and IgG classes in 4 (7%) patients and a rise in tTG concentrations in the IgA and IgG classes was seen in only 2 (3.5%) patients. CONCLUSION: In the patents first diagnosed with celiac disease, the detection rate of elevated levels of anti-DGP Abs in the IgA and IgG classes is 92.5 and 96.2%, respectively, and significantly indifferent from that of IgA and IgG anti-tTG Abs. The patients keeping GFD displayed a reduction in anti-DGP Abs. The high detection rate of IgA anti-DGP Abs in the patients first diagnosed with celiac disease allows this method to be recommended for immunological diagnosis of this disease in adults.

[Clinical immunological diagnostics of overlap syndrome during autoimmune hepatic disorders].

The complex determination of serum autoantibodies to hepatic antigens using enzyme immunoassay and immunoblot allows to increase the frequency of overlap syndrome identification during autoimmune hepatic disorders and its early diagnostics, that has a big clinical, diagnostic and prognostic importance. The levels of overlap autoantibodies combine with biochemical index and with disease activity and intensity of autoimmune processes during overlap syndrome of primary biliary cirrhosis/autoimmune hepatitis (PBC/AIH).

[Hypogammaglobulinemic sprue is a rare concurrence of primary immunodeficiency and celiac disease].

Hypogammaglobulinemic sprue (HGGS) belongs to orphan (rare) diseases. Its basis is a concurrence of primary immunodeficiency and celiac disease. The clinical picture of HGGS is characterized by recurrent bacterial infection foci, chronic diarrhea, and severe malabsorption syndrome (MAS). Immunological changes are exhibited by a decrease in the serum levels of γ-globulins (GG), immunoglobulins (Ig) A and G, and, to a lesser extent, IgM and B lymphocytes. The peculiarity of the morphological pattern of HGGS is the atrophy of the gastric mucosa and small bowel mucosal villi, which is accompanied by lymphocytic infiltration, formation of lymphoid follicles in the proper mucosal plate, and a drastic drop in plasma cells. It is precisely these signs that serve as a basis for identifying HGGS as an independent nosological entity. Its management is to be on a life-long gluten-free diet (GFD), to administer GG or Ig monthly, to correct metabolic disturbances, and to treat focal infections. The paper describes a case history of a female patient with HGGS. The disease was characterized by recurrent lung and kidney inflammatory foci concurrent with chronic diarrhea and grade 3 MAS. There was a dramatic reduction in GG, IgG, and IgA levels. Clinical remission and small intestinal mucosal structural recovery occurred due to GFD.

[Inflammatory nature of colon diverticula].

On the basis of morphological and immunological study of biopsies of the colon in patients with diverticulosis was revealed that microscopic inflammation of the mouth of the diverticulum is characterized by several features that include excessive proliferation of the epithelium, the predominance of macrophage reaction in the development of the immune response, increased cell adhesion and unusual ratio between the expression of cytokines and other regulatory molecules. Changes in the structure of the formed diverticula tissue are associated with dysregulation of many processes of tissue metabolism and morphogenesis. These include the dysregulation of cell renewal of the epithelium (increased level of proliferation of epithelial cells and inhibition of apoptosis), degradation of extracellular matrix components, moderate vascular reaction. All these processes take place on the background a particular form of immune protection and adaptation mechanisms.

[Gluten-sensitive celiac disease associated with recurrent aphthous stomatitis and schizophrenia].

The paper describes a clinical case of celiac disease with grade 3 malabsorption, which is associated with recurrent aphthous stomatitis and schizophrenia. On readmission after 8 months of strict adherence to his gluten-free diet, the patient was observed to be in clinical remission and to have normalized laboratory indices and immunological tests. The signs of recurrent stomatitis disappeared. However, the symptoms of the mental disease remained.

[Specific features of rehabilitation in patients with gluten-sensitivity celiac disease].

AIM: To elaborate recommendations for rehabilitation of patients with gluten-sensitivity celiac disease (GCD) on the basis of a long-term follow-up. SUBJECTS AND METHODS: Eighty-seven patients with GCD were followed up for as long as 31 years. Of those, 72.4% of the patients kept strictly to their gluten-free diet (GFD) throughout the follow-up; 9.2% did not follow the diet periodically; and 18.4% did not at all. The sera from 71 patients were tested for IgA and IgG anti-gliadin antibodies (AGAb) and anti-tissue transglutaminase antibodies (ATTGAb) at as long as 19-year follow-up. AGAb and ATTGAb were estimated by enzyme immunoassay (IMMCO Diagnostics). All the patients underwent endoscopic and histological examinations of the small bowel mucosa (SBM). RESULTS: To support the validity of keeping to the GFD, the time course of clinical, laboratory, and morphological changes were analyzed in 63 and 24 GFD followers and non-followers, respectively. The GFD non-followers were more frequently found to have diarrheic syndrome, symptoms of malabsorption syndrome, lower serum concentrations of hemoglobin, total protein, iron, and calcium; no SBM structural recovery was seen in any patient. When the GFD was long adhered to, there was also a reduction in detection rates and AGAb and ATTGAb concentrations. CONCLUSION: The adherence to the GFD was ascertained to contribute to fuller rehabilitation in the patients. However, even the patients who had strictly kept to their GFD showed periods of an exacerbation and incomplete SBM structural recovery. Therefore, the rehabilitation system for patients with GCD must involve diagnostic, therapeutic, and organizational measures that promote not only rapid clinical recovery, but also better quality of life in these patients.

Regeneration of colorectal epithelium in diverticulosis.

Excessive poorly differentiated epitheliocytes were detected in the crypts and subepithelial regions of the colorectal mucosa during the regeneration process in the majority of patients with diverticular disease. The compensatory reaction of the sigmoid mucosa decreased, which was seen from rarely detected cryptic hyperplasia. Disorders in the epitheliocyte proliferation and differentiation were paralleled by changes in tissue levels of proinflammatory cytokines (elevation of TNF-α and IFN-γ and reduction of IL-1ß and IL-8) and increase of IL-4, regulating lymphocyte activation.

[Generalized B-cell lymphoma, marginal zone masked by chronic liver disease].

This article describes a case of diagnosis of generalized B-cell lymphoma of marginal zone cells, which debuted with hepatolienal syndrome. Presented the latest information on etiology, pathogenesis, clinical manifestations, diagnostic methods and treatment of non-Hodgkin's lymphoma.

[Reproductive disorders in women with celiac disease. Effect of the etiotropic therapy].

UNLABELLED: Violation of reproductive function in patients with celiac disease can manifest as delayed puberty, infertility, amenorrhea, premature menopause, spontaneous abortion, low birth weight. The aim of the study was to establish the frequency and nature of reproductive function violation in patients with CD in the Russian Federation. MATERIALS AND METHODS: The study included 132 women (average age 38,5 +/- 1,17 years) with CD observed in CSRIG in the period from 2000 to 2010. Comparison group consisted 105 women (average age 38,7 +/- 1,6 years) with predominantly functional bowel disorders (irritable bowel syndrome, functional constipation, functional bloating, inert colon). Were took into account information regarding obstetric history, physical and laboratory signs of malabsorption syndrome (MS) study of antibodies to alpha-gliadin immunoglobulin (IG) A class (AGA) and tissue transglutaminase (AtTG). RESULTS: The average age of onset of menses was 14,3 +/- 1,4 years, and in the control group - 13,0 +/- 1,3 years (p > 0.05), half of patients with C (43.9%) had menstruation begun at age 15 years and older, while 7.6% of the women--aged 17 and older. In the comparison group menses beginning after 15 years was only at 13.3% of women. In 61.3% of patients with CD was irregular menstrual cycle while in the comparison group such violations were noted in 13.3% (p < 0.001). Prolonged periods of amenorrhea we observed in women with newly diagnosed GC 3 times more likely than the comparison group: 43.9% and 11.4% respectively (p < 0.01). They also had nearly 3 times more likely to occur spontaneous miscarriage: at 46.9% and 14.3% respectively (p < 0.01). The frequency of dead children birth was about the same: 2.3% and 1.9% respectively (p > 0.05). The frequency of reproductive disorders increased with the growth of the severity of MS. In 43% of women after 6-8 months of strict adherence to a gluten-free diet (GFD) had disappeared amenorrhea and there were regular menses. Three women of childbearing age, strictly abided the GFD and had a history of repeated spontaneous abortion during the year managed to get pregnant and give birth to healthy full-term baby. CONCLUSIONS: Reproductive disorders in women with celiac disease are significantly more likely than at women with functional bowel disease. One of the reasons of reproductive disorders in patients with CD can be malabsorption of necessary nutrients in the small intestine. The presence of reproductive disorders should be considered as a risk factor for celiac disease, so these women should be screened for celiac disease.