Vol 92, No 2 (2020)

Editorial
Systemic manifestations of inflammatory bowel diseases
Parfenov A.I., Kagramanova A.V., Knyazev O.V.
Abstract

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.

Terapevticheskii arkhiv. 2020;92(2):4-11
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European registry on Helicobacter pylori management (Hp-EuReg) as a tool to evaluate and improve clinical practice in Moscow
Bordin D.S., Voynovan I.N., Embutnieks Y.V., Nyssen O.P., Megraud F., O`Morain C., Perez-Gisbert J.
Abstract

Continuous evaluation of the actual clinical practice of diagnosis and treatment of Helicobacter pylori is crucial in order to provide the best standard of care and to compare health outcomes with expert recommendations.

Aim: to evaluate the effectiveness of the standard triple therapy (amoxicillin, clarithromycin, a proton pump inhibitor) and the standard triple therapy plus bismuth tripotassium dicitrate.

Materials and methods. Observational, prospective, multicenter study, carried out in one single Russian centre “A.S. Loginov Moscow Clinical Scientific Center” as part of the “Hp-EuReg”. Patients were included from 2013 to November 2019 by Russian gastroenterologists.

Results. A total of 647 patients were collected and 330 were administered either standard triple therapy ((amoxicillin, clarithromycin, a proton pump inhibitor) or standard triple therapy plus bismuth tripotassium dicitrate. Invasive methods is dominates in the initial diagnosis of H. pylori: the frequency of use of the quick urease test decreased from 50% in 2013 to 31% in 2019. Serology was used in 27.9%. There has been an increase in the use of the 13C-urea breath test from 13% in 2013 to 31% in 2019. The histological method (7.5%) and the stool antigen test (3.2%) were used less frequently. For eradication control non-invasive methods are mostly used: 13C-UDT (82.7%) and the stool antigen test (14.4%). The effectiveness of standard triple therapy (mITT) was 68% with a 7-day course, 79% with a 10-day course, and 70% with a 14-day course. Combination of bismuth and standard triple therapy eradicates H. pylori (mITT) in 63%, 75% and 89%, respectively.

Conclusion. An improvement in the clinical practice of managing patients with H. pylori infections has been noted. The standard triple therapy in combination with bismuth tripotassium dicitrate, prescribed for 14 days, is more effective.

Terapevticheskii arkhiv. 2020;92(2):12-18
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Esophageal disorders in patients with irritable bowel syndrome
Morozova Y.N., Pogromov A.P., Mnatsakanyan M.G., Tashchyan O.V., Kolosova K.Y.
Abstract

Aim. To study the whole range of esophageal disorders in patients with irritable bowel syndrome (IBS) using high-tech methods.

Materials and methods. 102 IBS patients (47 males, mean age 40.8, diagnosis of IBS was established according to Rome III criteria) with esophageal symptoms (heartburn, belching, globus sensation and noncardiac chest pain) were examined in gastroenterology department. All patients underwent endoscopy, with biopsies if required, X-ray examination of upper gastrointestinal tract; 24-hour pH-impedance monitoring; 13C-urea breath test. Evaluation of esophageal symptoms was carried out on the basis of Rome IV criteria.

Results. 21 (20.6%) individuals had esophagitis (ERD). According to 24-hour pH-monitoring data, 7 of them had overlap between GERD and functional esophageal disorders (FED). 27 (26.5%) individuals had nonerosive reflux disease (NERD). In 54 (52.9%) individuals endoscopy and pH-impedance monitoring data did not differ from normal, suggesting this group as group of patients with FED. There was no significant difference for age, sex and IBS subtypes in GERD, NERD and FED groups.

Conclusion. Comorbid esophageal disorders in patients with IBS are different and represented by organic diseases, FED and overlap between them. Methods such as 24-h pH-impedance measurement and esophageal manometry should be used to assess comorbid esophageal disorders in IBS patients.

Terapevticheskii arkhiv. 2020;92(2):19-23
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Diagnostic accuracy of predictive indexes of liver fibrosis in patients with chronic hepatitis C
Maev I.V., Kuznetsova E.I., Andreev D.N., Dicheva D.T.
Abstract

Aim. Assessment of the diagnostic accuracy of predictive indexes of liver fibrosis for the identification of severe fibrosis and cirrhosis (F3–F4) in patients with chronic hepatitis C (CHC).

Materials and methods. The retrospective design study included 127 patients with chronic hepatitis C (mean age 44.5±11.1 years). To assess the degree of liver fibrosis, all patients underwent transient elastography using a Fibroscan (EchoSens, France) and predictive indexes of liver fibrosis were calculated (APRI, FIB-4, discriminant Bonacini score). Transient elastography was considered as a reference method for assessing the degree of liver fibrosis for subsequent comparison of results with predictive fibrosis indixes.

Results. The sensitivity of the APRI index for the identification of severe fibrosis and cirrhosis of the liver (F3–F4) was 79%, and specificity was 69%. The FIB-4 index showed greater specificity (86%), but less sensitivity (68%). The sensitivity of the discriminant Bonacini scale was 81%, and the specificity was 77%. The positive predictive value of the APRI index, FIB-4 and the Bonacini scale for the identification of severe fibrosis and cirrhosis of the liver (F3–F4) in patients with chronic hepatitis C was 66; 78 and 72% respectively, and negative predictive value – 82; 78 and 84% respectively.

Conclusion. The results of this study indicate the relatively high diagnostic accuracy of a number of predictive indexes for evaluating liver fibrosis (APRI, FIB-4, discriminant Bonachini scale) in identifying severe fibrosis and cirrhosis of the liver (F3–F4) in patients with chronic hepatitis C.

Terapevticheskii arkhiv. 2020;92(2):24-28
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Evaluation of the effectiveness of differentiated therapy of non-alcoholic fatty liver disease
Vakhrushev Y.M., Suchkova E.V., Lukashevich A.P.
Abstract

Aim. Study of the effectiveness of differentiated therapy of non-alcoholic fatty liver disease taking into account the clinical and pathogenetic features of its course.

Materials and methods. 168 patients with non-alcoholic fatty liver disease were examined, 108 of them were women and 60 men aged from 30 to 70 years. For treatment, depending on the characteristics of the course of the disease, 3 groups of patients were formed. The first group included patients (n=47) with liver steatosis with a high content of lipids in the blood and an increased atherogenic coefficient; they received therapy with ursodeoxycholic acid with atorvastatin. The second group consisted of patients (n=65) with liver steatosis with an increased level of glycemia, insulin and insulin resistance, they were prescribed therapy with ursodeoxycholic acid and metformin. Patients of the third group (n=56) with steatohepatitis with concomitant bacterial overgrowth received еssentiale forte H therapy with rioflora immuno. Clinical data, blood biochemical parameters, insulin and HOMA-IR levels, intestinal microbiota status, as well as regression of liver steatosis and steatohepatitis were evaluated in the dynamics of treatment.

Results. In the dynamics of treatment, there was a decrease in the clinical manifestations of the disease in all observed groups of patients, an improvement in lipid metabolism and indicators of the functional state of the liver, a decrease in excessive bacterial growth. On the basis of ultrasound, elastography and fibrotest, the reverse development of liver steatosis was found in 20% and steatohepatitis in 66.6% of patients.

Conclusion. The data obtained indicate the feasibility of differentiated treatment of patients with non-alcoholic fatty liver disease depending on the characteristics of its course and stage.

Terapevticheskii arkhiv. 2020;92(2):29-33
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The long-term prospective study of patients with liver cirrhosis after elimination of the hepatitis C virus
Nabatchikova E.A., Abdurakhmanov D.T., Nikulkina E.N., Rozina T.P., Tanaschuk E.L., Nikiforova N.V., Adonyeva V.S., Moiseev S.V.
Abstract

Aim. To study liver function and portal hypertension, incidence and risk factors of liver-related complications, including hepatocellular carcinoma (HCC), in patients with HCV-related liver cirrhosis achieved sustained virologic response (SVR) after direct-acting antiviral therapy.

Materials and methods. Patients with HCV-related liver cirrhosis were followed up after achievement SVR with assessment of liver function parameters, portal hypertension, Model for End-stage Liver Disease (MELD) and Сhild – Pugh (CP) scores, complications development, including HCC, every 3–6 months. The median follow-up duration was 24 [18; 30] months after end of treatment.

Results. At last observation, a number of cirrhotic patients with CP class A increased from 72% to 85%, with CP class B reduced from 23.5% to 12.5%, with CP class C – from 4.5% to 2.5%. In 89% patients were identified a regress of liver fibrosis (from 23.5 [16.9; 28] to 15.0 [10.2; 21.3] kPa, p<0.005), each third patient – reduction of fibrosis stage to F2/F3. In 19 (9.5%) patients were occurred liver-related complications, including HCC (in 9 patients). Baseline high total bilirubin level (≥34 µmol/l) (Hazard ratio (HR) 11.5, 95% confidence interval (CI) 2.3–57.8, р<0.005) and ascites (HR=17.6, 95% CI 2.1–144.8, p=0.008) were independent risk factors associated with HCC development.

Conclusion. The risk of HCC development remains in patients with HCV-related liver cirrhosis, despite on eradication of hepatitis C virus. Therefore, these patients should continue to undergo more intensive examination (ultrasound examination and determination of alfa-fetoprotein level each 3–6 months), including contrast-enhanced methods of imaging, the frequency of which should be determined.

Terapevticheskii arkhiv. 2020;92(2):34-42
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Сlinical, immunological and morphological features in different types of autoimmune hepatitis
Sandler Y.G., Saliev K.G., Backih S.N., Khomeriki S.G., Khaymenova T.Y., Dorofeev A.S., Sbikina E.S., Vinnitskaya E.V.
Abstract

Due to the absence of the pathognomonic diagnostic criteria and to the diversity of clinical, serological and morphological manifestations, the diagnostic of the autoimmune hepatitis (AIH) remains to be a difficult task, which might lead to the delay of the timely beginning of the immunosuppressive therapy (IST), which in turn affects the disease outcomes.

Aim. To studying the clinical, biochemical, immunological and morphological markers in patients with seronegative (SN) and seropositive (SP) AIH and the qualities of their response to the IST.

Materials and methods. This retrospective cohort study included 82 AIH patients over the course of the years 2014–2019. All patients were selected in accordance with the criteria of the simplified assessment system of the IAIHG. Clinical, laboratorial and morphological characteristics of the AIH were analyzed. Therapy response was evaluated by the level of the ALT and IgG in 6–12 months after the start of the IST. The study material underwent statistical analysis using methods of parametrical and nonparametrical analysis. Statistical analysis was performed in the Statistica 13.3 (developed by StatSoft Inc., USA).

Results. 67/82 (81.70%) of the patients studied were women, median age of 54 years old [38; 70]. Patients with the diagnosis of the possible AIH according to the IAIHG made 85.4% (70 people). Almost everyone – 96% (79/82) – had morphological features of the interface-hepatitis with the lymphocytic/plasmocytic infiltration; emperipolesis was discovered in 63% of patients (49/82), hepatocellular rosette in 23% (19/82). Patients with SN AIH comprised 36.5% (30/82), with SP – 63.4% (52/82). Comparative analysis demonstrated that the clinical profile in patients with SN and SP AIH is the same, while the incidence of immuno-associated diseases is significantly higher in the group of seronegative AIH. The morphological profile in the two AIH groups is identical in both typical and “atypical” manifestations. The number of responders to IST was 63% (19/30) SN AIH vs 67% SP AIH (35/52), did not differ significantly (p=0.529).However, that the number of patients with liver cirrhosis in the SN AIH group was twice as big as the ones with SP: 37% vs 17% (p=0.089).

Conclusions. A comparative analysis of clinical, laboratory, morphological and clinical manifestations in the SN and SP AIH groups did not detected statistically significant significant differences, which may indicate that SN and SP AIH are the faces of one disease. It is possible that AB cannot be identified within the known spectrum of antibodies, or antibodies have slow expression, or are suppressed by the immune system. In any case, suspicions of AIH, in the absence of antibodies, it is recommended that liver biopsy be performed for the timely diagnosis of AIH and IST. Сirrhosis was more often diagnosed in the group SN AIH, which may be due to a later diagnosis, and therefore to untimely IST. The found frequent association of SN AIH with other immune-associated diseases requires a carefully study of this problem. The variety of clinical manifestations of AIH requires further study, the identification of clinical phenotypes with certain feature. This can help in the future to timely identify potentially problematic patients and predict a response to IST.

Terapevticheskii arkhiv. 2020;92(2):43-47
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Features of the course of gallstone disease in patients with non-alcoholic fatty liver disease
Cherkashchenko N.A., Livzan M.A., Krolevets T.S.
Abstract

Aim. To update information about comorbidity of non-alcoholic fatty liver disease (NAFLD) and gallstones disease (GD), evaluation of clinical and laboratory data, including insulin, leptin and adiponectin in individuals with NAFLD in combination with GD.

Materials and methods. According to the design, we conducted an open comparative study of 169 patients with NAFLD. The following comparison groups were formed: group 1 (n=95) – patients with NAFLD without GD, group 2 (n=35) – patients with NAFLD and GD and group 3 (n=39) – patients with NAFLD, GD and previous cholecystectomy.

Results. A high prevalence of coronary heart disease was found in the group of patients with GD and cholecystectomy (χ2=6.198, p≤0.05); positive, statistically significant correlation relationships of cholelithiasis, cholecystectomy with ischemic heart disease (rs=0.172, p≤0.05 and rs=0.241, p≤0.05, respectively). There was a statistically significant decrease in total bilirubin and total protein in patients of group 3 (H=7.376, p≤0.03 and H=6.345, p≤0.04). The level of leptin is statistically significantly higher and positively interrelated with cholecystectomy (H=5.812, p≤0.05, rs=0.313, p≤0.05).

Conclusion. Patients with NAFLD, GD and previous cholecystectomy have a high prevalence of coronary heart disease; the phenomenon of insulin and leptin resistance, high level of adiponectin were revealed in patients with NAFLD and gallstones; hyperleptinemia was observed among patients with NAFLD, GD after cholecystectomy.

Terapevticheskii arkhiv. 2020;92(2):48-54
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Hyperammonaemia in patients with chronic obstructive pulmonary disease and obesity: association mechanisms, detection rate and correction
Kozhevnikova S.A., Tribuntseva L.V., Budnevsky A.V.
Abstract

Chronic obstructive pulmonary disease (COPD) is a world-wide problem. It is characterized by comorbidity. Among the numerous comorbidity obesity is considered. The common pathogenetic factors cause the more severe course of COPD. Obesity is a complex metabolic condition affecting many physiological systems, in particular, the metabolic liver affection is developing in the type of non-alcoholic liver disease. In patients with different stages of non-alcoholic liver disease detoxification function is reduced. Toxic ammonia does not convert in urea. Ammonia begins to affect the whole organism.

Aim. To identify the frequency of hyperammonemia in patients with COPD and obesity, to analyze the degree of its influence on the COPD course and the quality of patients life, to assess the possibility of hyperammonemia correction with L-ornithine L-aspartate (LOLA).

Materials and methods. The study included 50 patients with non-acute COPD (GOLD 2), Group D, «phenotype with frequent exacerbations», central-type obesity. At the 1st stage of the investigation, COPD course was evaluated, specific evaluation tests (mMRC, CCQ, CAT, SGRQ, SF-36) were used, the biochemical blood test was performed, hyperammoniemia was detected on a Pocket Chem BA PA-4140, and Number Connecting Test was performed. In the 2nd stage of the investigation, all patients were prescribed a course of treatment with LOLA and after 4 weeks the estimated parameters were compared in dynamics.

Results. After 4 weeks, comparative analysis showed reliable positive dynamics of subjective assessment of weakness, 2 scales of SGRQ questionnaire, all scales of SF-36 questionnaire, as well as reliable reduction of ammonia level by 18.26 μmol/l, normal value of Number Connecting Test.

Conclusion. Detection of hyperammoniemia in patients with COPD and obesity and its correction with LOLA seems rational in order to reduce toxic effects of ammonia on organs and systems in this category of patients.

Terapevticheskii arkhiv. 2020;92(2):55-60
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Chronic pancreatitis with IBS-like syndrome: approach to therapy
Kozlova I.V., Bykova A.P., Osadchuk M.A.
Abstract

Aim. To determine approaches of the exacerbation’s treatment of chronic pancreatitis (CP) with IBS (irritable bowel syndrome)-like syndrome.

Materials and methods. 312 patients with exacerbation of CP were observed and received standard therapy: antispasmodics, enzymes, proton pump inhibitors. 85 (27.2%) patients had no response to treatment. After excluding obstructive CP, celiac disease, decompensation of diabetes (DD), ischemic and microscopic colitis, small intestinal bacterial overgrowth (SIBO) as a cause of abdominal pain and intestinal dysfunction, a group of 54 patients with exacerbation of CP and IBS-like syndrome was isolated. They were divided into 2 groups: group 1 – persons receiving with standard treatment of CP ciprofloxacin in a dose of 500 mg 2 times a day for 10 days (26 patients), group 2 – rifaximin 400 mg 3 times a day for 10 days (28 patients). The dynamics of clinical picture, biocenosis indices, endoscopic, morphological features of the colon, interleukin-2 (IL-2), IL-6, IL-8 concentration in the colon mucosa (CA) were evaluated.

Results. IBS-like syndrome was determined in 54 (63.5%) patients with prolonged (more than 4 weeks) exacerbation of CP. A modification of therapy is proposed with the results of clinical and instrumental, laboratory, bacteriological studies. 68% of patients with exacerbation of CP, receiving in addition to the standard regimen rifaximin, achieved clinical improvement, normalization of intestinal biocenosis, reduced concentrations of cytokines in tissues, reducing signs of chronic inflammation in the colon mucosa with reducing concentrations of IL-2, IL-6, IL-8 in colon mucosa (p<0.05).

Conclusion. Exacerbation of CP, resistant to standard therapy, may be associated with the formation of IBS-like syndrome. The inclusion of rifaximin in the complex therapy of prolonged exacerbation of CP contributes to the relief of intestinal dysfunction, abdominal pain of intestine, improves biocenosis, reduces inflammatory modifications, and reduces the concentration of cytokines in the colon mucosa.

Terapevticheskii arkhiv. 2020;92(2):61-66
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Vedolizumab in patients with inflammatory bowel diseases of in real clinical practice
Shapina M.V., Nanaeva B.A.
Abstract

Vedolizumab is currently the only selective biological drug for the treatment of inflammatory bowel diseases (IBD). Its effectiveness and safety has been shown in clinical trials. This article presents the experience of using vedolizumab in real clinical practice in patients with various forms of ulcerative colitis (UC) and Crohn’s disease (CD).

Materials and methods. 96 patients with IBD (62 with CD and 34 with UC) were prescribed therapy with vedolizumab at a dose of 300 mg intravenously at 0, 2, and 6 weeks, and further maintenance therapy was continued every 8 weeks. Most patients had prolonged inflammation (27 (79.4%) with total UC, 35 patients with CD (56.5%) had ileocolitis), resistance to therapy, including biological drugs (19 (55.9%) in patients with UC and 49 (79.0%) in patients with CD). The effectiveness of therapy was evaluated after 3 months (based on clinical response and clinical remission), 6 and 12 months (endoscopic response and endoscopic remission were additionally evaluated).

Results. After 3 months, clinical remission was observed in 62.5% and 36.6%, respectively. After 6 months, these indicators were 66.7% and 61.0%, and after 12 months, 70.8% and 61.0%, respectively. After 6 months, endoscopic remission was observed in 50.0% of UC patients and 26.8% of CD patients. After 12 months, it reached 58.3% and 31.7%, respectively. The analysis showed greater efficacy in bio-naive patients with CD (steroid-free remission after 12 months – 62.5%, endoscopic remission – 37.5%), as well as patients with non-stricturizing non-penetrating CD (58%). In patients with UC, vedolizumab showed the same effectiveness both in bio-naive patients (70.0%) and as a second-line therapy (71.2%). It turned out to be more effective in patients with moderate UC (76.2%) and steroid-dependent UC (77.8%).

Conclusions. Vedolizumab is effective in achieving clinical response and clinical remission, as well as endoscopic response and endoscopic remission in patients with UC and CD. Given the selective mechanism of action of the drug, it can be recommended as a first-line therapy.

Terapevticheskii arkhiv. 2020;92(2):67-73
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Clinical implications of chronic mesenteric ischemia in elderly and senile patients
Dolgushina A.I., Kuznecova A.S., Seljanina A.A., Genkel V.V., Vasilenko A.G.
Abstract

Aim. To evaluate the sensitivity and specificity of the clinical criteria for the diagnosis of chronic mesenteric ischemia in elderly and senile patients with mesenteric atherosclerosis.

Materials and methods. The study included 142 patients (82 men and 60 women). The median age of patients is 66.0 [62.0; 72.0] years.

Results. According to MDCT atherosclerotic lesions of the abdominal aorta and its unpaired visceral branches were diagnosed in 105 (73.9%) patients. A combination of atherosclerosis of the celiac trunk and the superior mesenteric artery with the presence of hemodynamically insignificant stenosis was revealed. Hemodynamically significant atherosclerotic narrowing of at least one mesenteric artery was present in 15% of cases. Among them, a single vascular lesion was found in 6 patients (4.2%), a combination of hemodynamically significant lesions of two arteries – in 15 (11%) patients. Depending on the clinical manifestations, all patients are divided into two groups: the first group – 30 (21.1%) patients with the presence of symptoms characteristic of chronic mesenteric ischemia (CMI). The second group consisted of 112 (78.8%) patients without a characteristic triad of symptoms. The clinical symptom complex of СMI, including postprandial abdominal pain, intestinal dysfunction and progressive weight loss, as a diagnostic criterion showed low sensitivity – 13.3% and specificity – 77.9%. At the same time, the sensitivity of such a clinical combination as a combination of atherosclerosis of the arteries of the lower extremities, weight loss and abdominal pain syndrome with a severity of more than 5.5 points, with respect to the detection of hemodynamically significant stenoses of two or more mesenteric arteries was sensitivity 86.7%, specificity 74.0%.

Terapevticheskii arkhiv. 2020;92(2):74-80
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Consensuns
Multidisciplinary treatment of the patient with a severe irritable bowel syndrome
Ruchkina I.N., Vyaznikova A.A., Indeykina L.K., Degterev D.A., Parfenov A.I.
Abstract

The patient E., aged 39, was described with a severe form of the irritable bowel syndrome that developed after the stress. In addition to the clinical manifestations of IBS, the patient got the somatoform disorders, which manifested itself with a large number of extraintestinal symptoms and led to a disability. According to the recommendations of the Rome Criteria IV 2016, the main medicines for the treatment of biopsychosocial model of IBS are antidepressants. The remission of the disease with a complete recovery of the patient’s disability was achieved by duloxetine, an antidepressant from the group of serotonin and noradrenaline reuptake inhibitors.

Terapevticheskii arkhiv. 2020;92(2):81-84
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Original articles
NSAID enteropathy
Kareva E.N.
Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used drugs in the world, and their side effects are very high. First of all, these are NSAID gastropathy, but in the long term, 50–70% of NSAIDs cause damage to the small intestine (NSAID enteropathy), sometimes with serious consequences. To date, no drugs have been proposed with proven effectiveness to prevent this side effect. Apparently, this is not due to the fully clarified mechanism of pathogenesis. The most promising is the hypothesis of the participation of individual representatives of microflora in the development of enteropathy. Therefore, modulating the intestinal flora with the help of probiotics can be the basic therapeutic strategy for the prevention and treatment of such damage.

Terapevticheskii arkhiv. 2020;92(2):85-92
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Bile acids are a risk factor for colorectal cancer
Krumz L.M., Gudkova R.B., Indejkina L.K., Sabelnikova E.A., Parfenov A.I.
Abstract

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.

Terapevticheskii arkhiv. 2020;92(2):93-96
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General and particular issues of etiopathogenesis of peptic ulcer and gastric cancer: current status of the problem
Osadchuk A.M., Davydkin I.L., Gricenko T.A., Osadchuk M.A.
Abstract

The development of peptic ulcer (PU) and gastric cancer (GC) is the result of the interaction of various internal and external factors. Moreover, if the role of Helicobacter pylori (H. pylori) in the development of diseases of the stomach is fully established, the significance of many other factors continues to be discussed. Serious controversy is caused by the participation of various strains of H. pylori in the development of PU and GC. First of all, these are Vac- and Cag-positive strains of H. pylori. The role of genetic human polymorphism in the development of this pathology is debatable. Especially the interleukin genes and necrotizing tumor factor alpha. The role of environmental factors in the formation of PU and GC is not fully understood. So, the role of alcohol, occupational hazards and drugs in the development of these diseases continues to be discussed. Further study of risk factors for various diseases of the stomach will optimize their prevention and treatment. The review presents a modern view of individual issues in the pathogenesis of PU and GC.

Terapevticheskii arkhiv. 2020;92(2):97-103
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Pharmacological and clinical feature of rebamipide: new therapeutic targets
Zvyaglova M.Y., Knyazev O.V., Parfenov A.I.
Abstract

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.

Terapevticheskii arkhiv. 2020;92(2):104-111
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Functional diseases of the gastrointestinal tract in the context with overlapping functional disorders: current status of the problem
Osadchuk M.A., Svistunov A.A., Kireeva N.V., Osadchuk M.M.
Abstract

Functional diseases of the gastrointestinal tract cause significant damage to the health care system. Their frequent combination in the same patient with the migration of clinical symptoms throughout the digestive tube is accompanied by continuous exacerbations, refractory to the therapy and severe psychosocial disorders. This review provides data on the main etiopathogenetic factors, clinical manifestations, course features and management tactics for patients with overlapping for the most common functional diseases of the gastrointestinal tract.

Terapevticheskii arkhiv. 2020;92(2):111-118
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Severe bronchial asthma patient care organization in various regions of the Russian Federation. From endotypes and phenotypes of bronchial asthma to personalized choice of therapy
Avdeev S.N., Volkova O.A., Demko I.V., Ignatova G.L., Leshchenko I.V., Kanukova N.A., Kudelya L.M., Nevzorova V.A., Nedashkovskaya N.G., Ukhanova O.P., Shulzhenko L.V., Fassakhov R.S.
Abstract

The meeting of the Expert board was held in Moscow on June 24, 2019, at which the following issues were considered: the applicability of a new terminology characterizing asthma endotypes and phenotypes in real clinical practice, the effect of phenotypes and biomarkers in patients with bronchial asthma on the choice of biological drug, as well as the optimal clinical profiles of patients for whom dupilumab is most effective, taking into account the data of the III phase clinical trials, regional features of medical care and changes in updated international clinical guidelines for the diagnosis and treatment of asthma. The Expert board included members of leading Russian scientific and educational medical institutions: S.N. Avdeev, corresponding member of the Russian Academy of Sciences, prof., MD; O.A. Volkova, Ph.D.; I.V. Demko, prof., MD; G.L. Ignatova, prof., MD; I.V. Leshchenko, prof., MD; Kanukova N.A.; Kudelya L.M., prof., MD; V.A. Nevzorova, prof., MD; N.G. Nedashkovskaya; O.P. Ukhanova, prof., MD; L.V. Shulzhenko, prof., MD; R.S. Fassakhov, prof., MD.

Terapevticheskii arkhiv. 2020;92(2):119-123
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