REVIEWS
Aim. To generalize up-to-date information on the possibilities of cytoprotection in the treatment and prevention of gastric and intestinal diseases, as well as to present the materials of an Expert Council meeting held on February 8, 2020 in Moscow under the support of the Alium company.
General provisions. The conducted Expert Council meeting was aimed at discussing the importance of improving the cytoprotective properties of the gastric and intestinal mucous membrane in the treatment of its lesions. It was shown that Rebamipide exhibits positive effects on various parts of the protective barrier of the gastrointestinal tract (GIT), primarily due to its stimulating action on the production of prostaglandins playing a key role in maintaining the cytoprotective properties of the gastrointestinal mucosa. The possibilities of applying Rebamipide for the treatment and prevention of erosive and ulcerative gastrointestinal lesions caused by non-steroidal anti-inflammatory (NSAIDs) and antithrombotic drugs were demonstrated. In the treatment of gastroesophageal reflux disease, Rebamipide is recommended for patients refractory to therapy with proton pump inhibitors (PPIs) and for those with non-acid reflux. The efficacy of Rebamipide in the treatment of Helicobacter pylori (H. pylori) infection, as well as functional dyspepsia and chronic gastritis, was confirmed.
Conclusions. Rebamipid is a highly effective drug positively affecting various cytoprotection links, thus being suitable for the treatment and prevention of erosive and ulcerative lesions of the gastrointestinal tract, as well as gastroenterological diseases of various etiologies.
Conflict of interest: The Expert Council meeting was supported by the Alium company.
Aim. To present literature data on the metabolic and genetic mechanisms of impaired fatty acid (FA) synthesis in the development and progression of non-alcoholic fatty liver disease (NAFLD).
General findings. NAFLD is a widespread disease progressing from steatosis to non-alcoholic steatohepatitis (NASH), increasing the risk of cirrhosis, liver failure and hepatocellular carcinoma. Progression of NAFLD and the development of NASH are closely related to lipid metabolism disorders caused not only by insufficient alimentary intake of fatty acids, but also by a decrease in the efficiency of their endogenous processing. The regulation of fatty acid metabolism involves enzymes desaturase (FADS1, FADS2) and elongase (ELOVL2 and ELOVL5) fatty acids. Desaturases are encoded by the FADS1 and FADS2 genes for fatty acid desaturases. Polymorphisms in the genes of fatty acid desaturases determine the effectiveness of PUFA endogenous processing. Violations in the activity of FADS1 and FADS2 and their genes are accompanied by dysregulation of the metabolic pathway involved in the biosynthesis of fatty acids. This leads to the damage of cell membranes, whose main components are represented by phospholipids. The progression of NAFLD is associated with the powerful toxicity of lipids released in the liver parenchyma upon the loss of the cell biomembrane integrity.
Conclusions. Further research into the NAFLD genetic mechanisms regulating the metabolism of fatty acids appears to be promising for a deeper understanding of the pathogenesis of this multifactorial disease.
ORIGINAL ARTICLES
Aim. To investigate the specific features of the expression of second-type melatonin receptors (MTNR1B) by epithelial cells of the distal esophagus in gastroesophageal reflux disease (GERD), depending on the severity of endoscopic changes in the mucous membrane.
Materials and methods. The study included 48 GERD patients, out of whom 37 and 11 people were suffering from non-erosive reflux disease (NERD) and erosive reflux disease (ERD), respectively. The control group consisted of 18 patients without GERD, comparable with the main groups by gender, age and body mass index. In order to determine the expression of MTNR1B, esophagogastroduodenoscopy with the collection of biopsy material from the mucous membrane of the distal esophagus was performed. The quantification of the MTNR1B expression intensity was carried out using the Aperio ImageScope_v9.1.19.1567 software. The level of melatonin metabolite, 6-sulphatehydroxymelatonin (6-SOMT), was determined in daily urine, as well as separately in daytime and nighttime portions.
Results. The intensity of MTNR1B expression by esophageal epithelial cells in patients with NERD demonstrated no difference with the control group (0.436 (0.123, 0.668) and 0.437 (0.202, 0.692), respectively; p> 0.05). A significant decrease in the expression of MTNR1B receptors was noted in patients with ERD compared to NERD patients (0.127 (0.059, 0.156) and 0.436 (0.123, 0.668), respectively; p = 0.017) and patients in the control group (0.437 (0.202, 0.692); p = 0.033). The low intensity of MTNR1B expression was associated with more pronounced endoscopic changes in the mucous membrane of the esophagus (r = –0.40; p = 0.0015). A statistically significant relationship was found between the expression intensity of MTNR1B and the level of melatonin in the daytime (r = 0.42; p = 0.018), as well as the night/day index reflecting the daily rhythm of melatonin synthesis (r = –0.43; p = 0.016).
Conclusions. The obtained data indicate that a decrease in the intensity of MTNR1B expression by esophageal epithelial cells can be considered as a prognostically unfavourable sign of the GERD course. The low intensity of MTNR1B expression is associated with a more severe (erosive) form of GERD and more pronounced endoscopic changes in the mucous membrane of the esophagus.
Aim. To study the composition of the intestinal microbiota in patients with chronic heart failure (CHF), as well as a relationship between the features of the CHF clinical course and changes in the microbial composition of the colon.
Materials and methods. The study included 60 heart failure patients with systolic dysfunction diagnosed according to the results of echocardiographic examination. The control group consisted of 20 patients comparable to the main group by gender, age and underlying diseases in the absence of CHF. In all patients, the severity of CHF symptoms was assessed using a clinical assessment scale. The levels of the N-terminal fragment of the cerebral natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) were determined. Echocardiographic examination and, if indicated, Holter ECG monitoring were performed. The intestinal microbiota in stool samples was studied by sequencing the 16S gene of ribosomal RNA (rRNA).
Results. In comparison with the control group, CHF patients showed a decrease in the relative content of Tenericutes (p = 0.02, Mann—Whitney test) and an increase in the proportion of Euryarchaeota (p = 0.02) and Firmicutes (p = 0.03). At the family level, an increase in the proportion of Methanobacteriaceae (p = 0.03) and a decrease in the proportion of Pseudomonadaceae (p = 0.01) and Moraxellaceae (p = 0.01) were noted. No dependence of the intestinal microflora composition on the functional class of heart failure was observed. However, a correlation was revealed between the relative number of certain bacterial families and the severity of impaired contractile function, the level of the inflammatory marker and the biochemical marker of heart failure.
Conclusions. The obtained data indicate differences in the intestinal microbiota composition in patients with and without heart failure. A correlation between the number of some bacterial families and various laboratory and instrumental indicators assessed in heart failure patients was revealed. Further research into the effect of intestinal microbiota on the course of heart failure appears to be promising for improving treatment methods.
The aim of this study was to assess the usefulness of endoscopic removal of small (less than 10 mm) colon polyps with a cold snare on the basis of endoscopic microstructural analysis of the edges of the post-resection defect using high-resolution video endoscopic equipment.
Methods. In 74 patients (22 men and 52 women) aged 28 to 84 years (average age 59.3 ± 3.6 years), 103 colon polyps of types 0-IIa — 82 (79.7 %) and 0-Is — 21 (20.3 %), without the signs of severe dysplasia and cancer, were removed through the endoscope by the using of a cold snare, followed by mandatory inspection of the edges of the post-resection defect. A complete endoscopic analysis of the microstructures and the capillary vessels of the mucosa was performed on the edge of the post-resection defect, and then was compared to the histological image.
Results. The endoscopic criteria for completely performed cold snare resection were identified, they are parallel crypts and the structure of intestinal pits of type I (S. Kudo) in the edge of the post-resection defect, which were observed in 93 (90.3 %) cases. Signs of residual tissue were dilated altered crypts with a violation of the parallelism of their location, which were observed in 10 (9.7 %) cases. The difference between the spatial location of crypts in the rectum (the effect of “falling crypts”) was identified, which complicates the differential diagnosis of normal and residual tumor tissue. In the endoscopic diagnosis of the vascular pattern of the colon mucosa was determined that flat-elevated polyps have a fine capillary network, which reduces the risk of bleeding when use a cold resection method. An observation (diagnostic colonoscopy) was performed in 11 (10.7 %) patients, including a case with the polyp with high grade displasia. No advance adenomas and interval cancers were detected.
Conclusion. Тhis research helps to ensure reliable diagnosis of the completeness of performed endoscopic intervention and the possibility of removal of residual tumor tissue (if present) immediately after its completion, it’s allow a reduction in the number of recurrences of tumors.
Aim. To identify trends in the structure of patients with liver diseases, in particular hepatocellular cancer (HCC), by analysing the experience of two specialised medical centres.
Materials and methods. A retrospective analysis of the medical records of hepatological patients who sought medical treatment at to the V.Kh. Vasilenko Clinic of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology of the Sechenov University in 2013, 2014 and 2017 (total 2459 patients) was carried out. The number of patients with chronic viral hepatitis (CVH) was 651, with non-alcoholic fatty liver disease (NAFLD) — 590, with alcoholic liver disease (ALD) — 66, with autoimmune liver diseases — 416, with liver cirrhosis (LC) of any etiology 407, other liver diseases — 329. A retrospective analysis of the medical records of patients with HCC who were examined and treated at the N.V. Sklifosovsky Research Institute for Emergency Medicine in the period from 2008 to 2017 (n = 86) was carried out.
Results. The ratio of patients with chronic hepatitis C and B in 2013–2017 significantly changed. An almost twofold decrease in the number of patients with chronic hepatitis C (210 patients in 2013 and 141 patients in 2017) and an increase in the number of patients with chronic hepatitis B (20 patients in 2013 and 45 patients in 2017) was observed. An almost twofold increase in the total number of NAFLD patients was detected (163 patients in 2013 and 276 patients in 2017). The number of ALD patients increased from 12 patients in 2013 to 31 patients in 2017. The proportion of patients with autoimmune liver diseases in the overall structure of patients who applied to the department was 20 % in 2013, 13.6 % in 2014 and 10.8 % in 2017. An almost twofold decrease in the number of patients with alcoholic LC and LC associated with HBV was observed (73 patients and 17 patients in 2013 and 38 patients and 6 patients in 2017, respectively) as well as a noticeable increase in the number of patients with alcoholic LC and LC associated with HCV (6 patients and 51 patients in 2013 and 26 patients and 75 patients in 2017, respectively). In the analysis of HCC patients, the ratio of men to women was 3:1 (64 men and 22 women), the median age was 54.5 years (IQR 48–59). The median time from the establishment of chronic liver disease to the detection of HCC was 7.5 years (IQR 3–14.5). In 86 % of cases, the HCC development was preceded by cirrhosis (Child-Pugh A: n = 24; Child-Pugh B: n = 30; Child-Pugh C: n = 20), in 14 % — by chronic hepatitis. Viral liver lesions were the leading cause of HCC in 79 % (n = 68), ALD in 4 % (n = 3), NAFLD in 1 % (n = 1), AIH in 1 % (n = 1). In 10 % (n = 9), a combined liver lesion was observed, in 5 % (n = 4), no previous liver disease was known. The highest five-year survival rate (100 %) was found in the group of patients who received antiviral therapy (AVT) before and after liver transplantation.
Conclusions. NAFLD, ALD, and chronic hepatitis B patients began to seek medical help more frequently. An increase in the number of patients with autoimmune LC and LC associated with chronic hepatitis C virus (HCV) infection was observed. The conducted analysis of trends in the structure of HCC patients showed that chronic HCV and HBV infection is the main prerequisite for the development of cancer. Liver transplantation is the most effective treatment for HCC. AVT before and after liver transplantation allows a statistically significant increase in the five-year posttransplant survival of HCC patients with chronic hepatitis C to be achieved.
NATIONAL COLLEGE OF GASTROENTEROLOGY, HEPATOLOGY
Aim. To provide a definition and classification of nutraceutical products and to show their significane in modern integrative medicine.
Background. Nutraceuticals are foodstuffs and their components, which have a positive effect on human health, including preventive maintenance and treatment of diseases. Nutraceuticals include healthy and functional foods, as well as biologically active food additives (BAFA). Healthy foods are nutritional foodstuffs without any artificial modification. These include organic, whole, and natural foods. Alongside a high nutritional value, functional food products have a positive effect on the human body due to functional food ingredients. BAFAs are food additives that contains one or several food ingredients (vitamins, mineral substances, plant components, amino acids and others). Specialists express conflicting viewpoints concerning nutraceuticals. Some nutraceuticals, such as probiotics, have confirmed their effectiveness in clinical trials, while the beneficial properties of others require further elucidation.
Conclusions. The application of nutraceuticals, as well as their combined use with pharmaceuticals, in accordance with recommendations by scientific professional associations formulated on the basis of valid research studies can lead to an improvement in the quality of the life and longevity of the population. This position forms a basis for the development of integrative medicine — a contemporary approach to the treatment of diseases.
CLINICAL GUIDELINES
Aim. To provide practical recommendations on the use of probiotics for the treatment and prevention of gastroenterological diseases in adults.
General provisions. Probiotics are living microorganisms that benefit the health of the host when administered in adequate amounts. The main functions of probiotics include the support for colonisation resistance, the metabolism of food substrates and utilisation of end metabolites, the production of substrates necessary for the macro-organism, as well as the regulation of local and adaptive immune responses. Probiotics can be registered in the Russian Federation as biologically active food additives (BAFA) or as pharmaceutical products (drugs) in accordance with the microbiological standards and legislative requirements of the Russian Federation. The probiotics registered in the Russian Federation as BAFA for adults include bacteria of the Lactobacillus, Bifidobacterium, Enterococcus, Pediococcus, Lactococcus, Streptococcus, Bacillus, and Escherichia genera, and fungi of the Saccharomyces genus; probiotics registered as drugs — bacteria of Lactobid, Lactobacid, Escherichia and Enterococcus genera and fungi of the Saccharomyces genus. Some probiotics registered in the Russian Federation include probiotic strains that have proved to be effective for the prevention and treatment of antibiotic-associated diarrhea, the prevention of C. difficile-associated disease, the eradication of H. pylori infection, as well as for the treatment of irritable bowel syndrome and functional constipation.
Conclusions. The clinical efficacy of probiotics depends on the probiotic strains included in their composition and is confirmed by a comparative analysis of the results of appropriate clinical studies. Not all probiotics registered in the Russian Federation as BAFA or drugs contain bacterial or fungal strains; as a result, the expected clinical effect may not be achieved.
ISSN 2658-6673 (Online)