Vol 95, No 2 (2023)

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Full Issue


Abdominal pain

Parfenov A.I.


Abdominal pain is a symptom that determines the accuracy and timeliness of diagnosis, treatment, and prognosis. The article describes the causes of acute and chronic abdominal pain, particularly the pain in the abdominal wall, and the challenges in recognizing them. The pathogenetic features of visceral, parietal, referred, and psychogenic pain and the principles of symptomatic therapy are addressed. It is emphasized that complex invasive examinations of the abdominal organs are especially relevant for elderly patients who often have conditions that require computed tomography, including contrast-enhanced scans. Without losing the importance of modern examination methods used in clinical practice, the author states that a detailed medical history and a thorough physical examination can significantly narrow the work-up. Endoscopic and other instrumental invasive examinations should be strictly justified and applied with a cost-effective rational approach.

Terapevticheskii arkhiv. 2023;95(2):113-119
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Original articles

Effectiveness of empirical Helicobacter pylori eradication therapy with furazolidone in Russia: results from the European Registry on Helicobacter pylori Management (Hp-EuReg)

Bordin D.S., Voynovan I.N., Sarsenbaeva A.S., Zaytsev O.V., Abdulkhakov R.A., Bakulina N.V., Bakulin I.G., Osipenko M.F., Livzan M.A., Alekseenko S.A., Tarasova L.V., Tarasova G.N., Bogomolov P.O., Maev I.V., Andreev D.N., Abdulkhakov S.R., Starostin B.D., Bakanova N.V., Kononova A.G., Kolbasnikov S.V., Bueverova E.L., Moreira L., Megraud F., O'Morain C., Perez Nyssen O., Gisbert J.


Background. First-line therapy does not always provide a high level of Helicobacter pylori eradication due to the increase of H. pylori resistance to antibiotics; therefore, it remains necessary to identify the most effective rescue treatments. The purpose of this study was to evaluate the efficacy and safety of empirical H. pylori furazolidone-containing regimens.

Materials and methods. Adult H. pylori infected patients empirically treated with furazolidone-containing eradication regimens were registered in an international, prospective, multicenter non-intervention European registry on H. pylori management (Hp-EuReg). Data were collected at AEG-REDCap e-CRF from 2013 to 2021 and the quality was reviewed. Modified intention-to-treat (mITT) effectiveness analyses were performed.

Results. Overall 106 patients received empirical furazolidone-containing therapy in Russia. Furazolidone was prescribed in a sequential scheme along with amoxicillin, clarithromycin and a proton pump inhibitor in 68 (64%) cases, triple regimens were prescribed in 28 (26%) patients and quadruple regimens in 10 (9.4%). Treatment duration of 7 days was assigned to 2 (1.9%) patients, 10-day eradication therapy in case of 80 (75%) and 14 days – in 24 (23%) patients. Furazolidone was mainly used in first- (79%) and second-line (21%) regimens. The methods used to diagnose H. pylori infection were: histology (81%), stool antigen test (64%), 13C-urea breath test (6.6%), and rapid urease test (1.9%). The mITT effectiveness of sequential therapy was 100%; 93% with the triple therapy and 75.5% with quadruple therapy. Compliance was reported in 98% of cases. Adverse events were revealed in 5.7% of patients, mostly nausea (3.8%). No serious adverse events were reported.

Conclusion. Furazolidone containing eradication regimens appear to be an effective and safe empirical therapy in Russia.

Terapevticheskii arkhiv. 2023;95(2):120-129
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Comparative analysis of the intestinal microbiota in patients with exocrine pancreatic insufficiency of various severity

Maev I.V., Levchenko A.I., Galeeva J.S., Andreev D.N., Osipenko J.V., Bordin D.S., Ilyina E.N.


Background. Exocrine pancreatic insufficiency (EPI) is a critical host factor in determining the composition of the gut microbiota. Diseases that cause exocrine insufficiency can affect the gut microbiome, which can potentiate disease progression and complications. To date, the relationship of exocrine insufficiency in various pancreatic (PA) pathologies, in chronic pancreatitis (CP), with dysbiotic changes in the intestinal microbiota (IM) has not been reliably studied. The available data are heterogeneous and contradictory, which determines the need for further research.

Aim. To conduct a comparative analysis of the taxonomic composition of the intestinal microbiota in patients with CP of various etiologies, without or with the presence of EPI of varying severity, as well as patients with severe EPI with a history of surgical intervention (SI) on the pancreas.

Materials and methods. A total of 85 patients were included in the study. Patients were divided into groups according to the severity of EPI: Group 1 (n=16) – patients with CP without EPI; Group 2 (n=11) – patients with CP and mild EPI; Group 3 (n=17) – patients with severe CP and EPI; Group 4 (n=41) – severe EPI in persons with a history of SI on the pancreas. Verification of CP was carried out according to clinical, anamnestic and instrumental data. The degree of EPI was determined by the level of pancreatic elastase-1 (PE-1) feces. Informed consent for the study was obtained for each patient, an anamnesis was collected, physical and laboratory examinations were performed, and a stool sample was obtained. DNA was extracted from each stool sample, the taxonomic composition of BM was determined by sequencing the bacterial 16S rRNA genes, followed by bioinformatic analysis.

Results. We followed the changes in the gut microbiota from a group of patients with CP without EPI to a group with severe EPI, in those who underwent SI. At the level of the phylum, the IM of all groups showed the dominance of Firmicutes, with the lowest representation in the severe EPI group, both with SI and CP, and the growth of the Actinobacteria, Verrucomicrobiota and Fusobacteria types. The differential representation of childbirth varied: in patients with severe EPI and CP, compared with mild, statistically significant genera – Akkermansia, Ruminococcus gauvreauii group and Holdemanella; compared with CP without exocrine insufficiency, Prevotella, Ruminococcus gauvreauii group, Peptostreptococcus and Blautia dominated. The CP group with mild EPI was dominated by the following genera: Lachnospiraceae_ND 2004 group, Faecalitalea, Fusobacterium, Catenibacterium, Roseburia, Atopobium, Cloacibacillus, Clostridium innococum group, Ruminococcus torques group. All groups showed a low diversity of taxa with a predominance of opportunistic flora, including participants in oncogenesis.

Conclusion. The results of the study show that patients with CP of various etiologies and patients with severe EPI who underwent specific intervention on the pancreas have intestinal microbiota dysbiosis, the severity of which is significantly influenced by the degree of EPI.

Terapevticheskii arkhiv. 2023;95(2):130-139
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The effect of the FODMAP and rebamipid diet on the activity of disaccharidases in patients with enteropathy with impaired membrane digestion

Baulo E.V., Belostotsky N.I., Akhmadullina O.V., Dbar S.R., Bykova S.V., Parfenov A.I.


Aim. To compare the effect of a diet low in fermentable oligo-, di-, monosaccharides and polyols (fermentable oligosaccharides, disaccharides, monosaccharides and polyols – FODMAP) and rebamipide on carbohydrate tolerance and disaccharidases activity in patients with maldigestive enteropathy (ENMP).

Materials and methods. The study included 61 patients with ENMP with reduced small intestine carbohydrases. Their glucoamylase activity was 100 ng glucose/mg tissue × min (quartile 53, 72), maltase – 504 (quartile 258, 708), sucrase – 43 (quartile 25, 58), lactase – 8 (quartile 4, 20). Group 1 included 19 people on a low FODMAP diet. The 2nd group included 42 patients who were on a normal diet and received rebamipide 300 mg/day. Patients were monitored weekly for 8 weeks.

Results. In 16 patients of the 1st group, abdominal pain and stool disorders decreased, in 15 patients, swelling and rumbling in the abdomen stopped. Glucoamylase activity increased to 196 (quartile 133, 446, р<0.024) ng glucose/mg tissue × min, maltase activity increased to 889 (quartile 554, 1555, p<0.145), sucrase activity increased to 67 (quartile 43, 175, p<0.039), lactase activity increased to 13 (quartile 9, 21, p<0.02). After the diet was discontinued, intestinal symptoms in patients of group 1 resumed. In 27 patients of the 2nd group after 4 weeks dyspeptic manifestations decreased, in 34 patients the tolerability of products containing FODMAP improved. Continuation of treatment up to 8 weeks contributed to a further improvement in well-being. Glucoamylase activity increased after 4 and 8 weeks to 189 (quartile 107, 357, p<0.013) and 203 (quartile 160, 536, p<0.005), respectively; maltase – up to 812 (quartile 487, 915, p<0.005) and 966 (quartile 621, 2195, р<0.0012); sucrases – up to 60 (quartile 34, 105, p<0.013) and 75 (quartile 52, 245, р=0.003); lactase – up to 12 (quartile 8, 12, p<0.132) and 15 ng glucose/mg tissue × min (quartile 10, 20, р<0.092).

Conclusion. The clinical symptoms of fermentable carbohydrate intolerance and increased membrane enzyme activity are reduced by a low FODMAP diet in patients with ENMT, but clinical symptoms of food intolerance reappear when switching to a normal diet. Treatment with rebamipide improves food tolerance and consistently increases the activity of TSOTS enzymes after 4 and 8 weeks.

Terapevticheskii arkhiv. 2023;95(2):140-144
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The course and clinical manifestations of Peutz–Jeghers syndrome in the Russian population

Savelyeva Т.A., Ponomarenko А.A., Shelygin Y.A., Kuzminov А.M., Vyshegorodtsev D.V., Loginova А.N., Pikunov D.Y., Goncharova Е.P., Likutov А.A., Mainovskaya О.A., Tsukanov А.S.


Background. Peutz–Jeghers syndrome (PJS) is a rare hereditary syndrome characterized by the growth of hamartomatous polyps in the gastrointestinal tract, perioral pigmentation and an increased risk of malignant neoplasms. The syndrome is caused by a pathogenic variant in the STK11 gene.

Aim. To assess the clinical picture and treatment of Russian patients with PJS.

Materials and methods. A retrospective analysis of 30 patients from 25 families with an established diagnosis of PJS who were in the Ryzikh State Scientific Center for Coloproctology from 2011 to 2021 was carried out. All patients underwent instrumental examination, including esophagogastroduodenoscopy, colonoscopy, X-ray examination of the small intestine/CT-enterography, in the absence of invaginates – video capsule endoscopy, as well as molecular genetic examination for the presence of pathogenic variants in the STK11 gene. All removed polyps were subjected to the histological examination.

Results. The analysis of the clinical picture allowed us to establish the following data: the first complaints in patients were noted in childhood and adolescence, while the median age was 11 [7; 19] (0.5–24) years; pathogenic variants in the STK11 gene were identified in 26 (87%) cases, among which 10 were described for the first time; during the initial examination, polyps in the small intestine were detected in all 30 (100%) patients, in the stomach – in 23/30 (77%) patients, and in the colon – in 21/30 (70%); with an age, an increase in the number of polyps in all parts of the gastrointestinal tract was noted; before the diagnosis operations were performed urgently for intestinal obstruction; after the diagnosis of PJS, when polyps were detected in the gastrointestinal tract, endoscopic polypectomies were performed; if endoscopic removal of hamartomatous polyps was impossible, patients were operated as planned; malignant diseases of the predominantly reproductive system were detected in 8/30 (27%) patients. The median age of cancer detection was 52 [31; 52] (17–59) years.

Conclusion. Russian patients with PJS have population-specific features in the clinical picture of the course of the disease, which dictates the need to develop their own recommendations for monitoring and treatment of such patients.

Terapevticheskii arkhiv. 2023;95(2):145-151
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Features of the upper gastrointestinal tract mucous membrane state in patients with atherosclerosis of the mesenteric arteries

Selyanina A.A., Dolgushina A.I., Kusnezowa A.S., Genkel V.V., Olevskaya E.R., Nikushkina K.V., Khikhlova A.O.


Aim. To evaluate the clinical and endoscopic features of diseases of the upper gastrointestinal tract (GIT) in patients with atherosclerosis of the mesenteric arteries (MA).

Materials and methods. The study included 48 patients with atherosclerosis of MA and 43 patients without atherosclerosis of MA, who were hospitalized in the department of vascular surgery of the Chelyabinsk Regional Clinical Hospital in the period from 2019 to 2021. All patients underwent multispiral computed tomoangiography of the visceral and lower limb arteries, esophagogastroduodenoscopy.

Results. Assessment of lesions of the upper gastrointestinal tract revealed a higher incidence of erosive and ulcerative gastroduodenopathies among patients with atherosclerosis of MA (60.4%), compared with patients without atherosclerosis MA (39.5%); p=0.047. Signs of severe atrophy according to the data of histological examination were statistically significantly more frequent among patients with atherosclerosis of MA (29.2 and 11.6%; p=0.031). According to the results of logistic regression, the following predictors of erosions and ulcers of the upper gastrointestinal tract were revealed: the severity of stenosis of the superior mesenteric artery (SMA) is more than 35%, the body mass index (BMI) is less than 25.9 and the total score on the HADS scale is more than 6.5 points for depression (p=0.008).

Conclusion. Erosive-ulcerative gastroduodenopathies and atrophy of the gastric mucosa are significantly more common in the group of patients with MA atherosclerosis. The main risk factors for erosions and ulcers of the upper gastrointestinal tract in patients with MA atherosclerosis are: the severity of SMA stenosis is more than 35%, a decrease in BMI is less than 25.9 and an increase in the HADS score is more than 6.5 points.

Terapevticheskii arkhiv. 2023;95(2):152-157
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Liver damage in children and adolescents with newly diagnosed celiac disease: clinical and anamnestic, serological and morphological patterns

Cherkasova E.A., Klimov L.Y., Kuryaninova V.A., Yagupova A.V., Ivenskaya T.A., Gliva A.V.


Hypertransaminasemia is a common extra-intestinal manifestation of celiac disease.

Aim. To analyze the frequency of hypertransaminasemia, clinical and anamnestic, serological and morphological picture in children in the active period of celiac disease.

Materials and methods. The study included 272 children with celiac disease aged from 8 months to 17 years. The patients were divided into two groups: the first – children with hypertransaminasemia, the second – without hypertransaminasemia.

Results. Hypertransaminasemia was detected in 55.9% of children with celiac disease. The age of manifestation of the disease in the first group was 1.0 [0.5; 2.0] years, in the second group – 1.9 [0.5; 4.0] years (p=0.0004). Children of the first group were diagnosed at 2.5 [1.7; 4.9] years, the second group – at 4.9 [3.0; 10.8] years (p<0.001). The duration of the latency period in children of the first and second groups was 1.4 [0.6; 3.1] years and 2.4 [0.9; 4.3] years, respectively (p=0.002). The average values of IgA anti-tTG antibodies in children of the analyzed groups did not differ, and the indicators of IgG anti-tTG antibodies in the first group were 1.6 (p=0.04) times higher. The level of EMA in children with hypertransaminasemia was 2 times higher than in children without hypertransaminasemia.

Conclusion. Hypertransaminasemia is more often detected in young children with early manifestation of the disease, increases with the deepening of atrophy in the mucous membrane of the small intestine. Higher titers of celiac-specific antibodies were detected in children with hypertransaminasemia.

Terapevticheskii arkhiv. 2023;95(2):158-163
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Irritable bowel syndrome phenotypes: leading factors of genetics and epigenetics, mechanisms of formation

Gaus O.V., Livzan M.A.


Aim. To develop individualized approaches to the treatment of irritable bowel syndrome (IBS) based on the interaction of genetic and epigenetic factors, to characterize the phenotypes of the disease.

Materials and methods. According to the formulated concept of the authors, from the cohort of patients with IBS, subgroups were distinguished – “post-infectious IBS” (n=45), “IBS in overweight and obese people” (n=49), “comorbid IBS” (n=75) and “essential IBS” (n=51). In each subgroup the prevalence of candidate gene polymorphisms associated with IBS (COMT, SLC6A4, FTO), nutritional habits, levels of anxiety and depression, secretion of cortisol, serotonin, dopamine and zonulin levels in feces were studied.

Results. Patients with “post-infectious IBS” are characterized by the carriage of the S allele of the SLC6A4 gene, the val/val genotype of the COMT gene, the prevalence of diarrhea, a high level of anxiety and frequent refusal of milk and dairy products. The phenotype “IBS in overweight and obese individuals” is characterized by L/L genotypes of the SLC6A4 gene, met/met of the COMT gene and A/A of the FTO gene, constipation, low plasma dopamine levels, signs of depression, frequent episodes of overeating, addiction to fatty and sweet foods, excessive consumption of sugar, lack of vegetables in the diet. The “comorbid IBS phenotype” is characterized by more frequent detection of the val/val genotype of the COMT gene and the carriage of the S allele of the SLC6A4 gene, clinically pronounced anxiety and depression, early onset of the disease, severe course, significant food restrictions and significant increase in epithelial permeability. With the “essential phenotype”, there are no bright stigmas of the disease; it is not possible to identify distinctive genetic and epigenetic factors, as well as the leading pathogenetic mechanism.

Conclusion. The analysis of genetic and epigenetic factors, the leading mechanisms of the formation and course of IBS allows us to identify additional (except for “postinfectious”) phenotypes of the disease: “IBS in overweight and obese people”, “comorbid” and “essential”.

Terapevticheskii arkhiv. 2023;95(2):164-172
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Assessment of the possible impact of hepatitis viruses on the development and course of autoimmune liver diseases

Sbikina E.S., Vinnitskaya E.V., Batskikh S.N., Sandler Y.G., Saliev K.G., Khaimenova T.Y., Bordin D.S.


Background. Despite the well-studied pathogenesis, the etiology of autoimmune liver disease (AILD) remains unknown.

Aim. To determine the significance of hepatitis A, B, C and E viruses in the development and progression of AILD.

Materials and methods. A single-center case-control study included 139 patients with AILD: autoimmune hepatitis – AIH (n=46), primary biliary cholangitis – PBS (n=74), primary sclerosing cholangitis – PSC (n=19). Median age 56 years, IQR 48–65 years. 125 patients – without liver disease – control group (median age 55 years, IQR 46–65 years). Testing of blood serum samples for anti-HAV IgG, anti-HEV IgG, HBsAg, anti-HBc IgG, anti-HCV was carried out by solid-phase ELISA. All patients underwent fibroelastography. Needle liver biopsy – 70 patients: AIH (n=37), PBC (n=28) and PSC (n=5).

Results. Ab(IgG) to HAV and HBV were detected in patients with AILD significantly more often than in the control group (74.8% vs 54.4%; p<0.001). An increased risk of developing AILD was established in patients with the presence of antibodies to HAV, HBV and HEV (OR 2.491, CI 95% [1.481–4.190]). The highest risk of developing PBC was found in patients with antibodies to HAV and HBV (OR 3.008, 95% CI [1.633–5.542] and OR 2.515, 95% CI [1.242–5.093]). In patients with severe liver fibrosis (F3–F4 according to METAVIR), antibodies to HAV and HBV were detected significantly more often than in patients with F0–F2 [85% vs 65%; p=0.008].

Conclusion. In our work, we have demonstrated the relationship of past hepatitis A, B, E and AILD, as well as the high risk of developing severe fibrosis in patients with AILD and markers of hepatitis A and B viruses indicates the possible involvement of these viruses in the pathogenesis of AILD.

Terapevticheskii arkhiv. 2023;95(2):173-178
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Clinical notes

Difficulties in diagnosing intestinal T-cell lymphoma. Case report

Gadaev I.Y., Ershov V.I., Kovrigina A.M., Sokolova I.Y., Tashyan O.V., Mingalimov M.A., Antyufeeva O.N., Budanova D.A., Mnatsakanyan M.G., Bochkarnikova O.V., Nagornaia D.S.


The article describes a rare diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), due to its veiled by a number of so-called “masks” of enteropathies. A detailed analysis of all clinical, morphological and immunohistochemical data made it possible to establish the correct diagnosis. The revealed pathology is extremely rare in practice, even among specialists in hematology. The article demonstrates the main stages of both a complex diagnosis and an attempt at therapy for this aggressive form of intestinal lymphoma.

Terapevticheskii arkhiv. 2023;95(2):180-186
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Principles of treatment of different forms of alcoholic liver disease: A review

Raikhelson K.L., Kondrashina E.A., Pazenko E.V.


The review considers the principles of treatment of various forms of alcoholic liver disease from the point of view of the evidence base and clinical recommendations. The main therapy for severe alcoholic hepatitis is systemic glucocorticosteroids, their effect on survival is increased by the addition of antioxidants (N-acetylcysteine, ademethionine). The effect of ademetionine on the life expectancy of patients with alcoholic cirrhosis of Child–Pugh class A and B has been proven. The treatment of patients with mild forms of alcoholic liver disease is not well developed, and the evidence base for most of the drugs used is modest.

Terapevticheskii arkhiv. 2023;95(2):187-192
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History of medicine

Crohn disease: before and after 1932 year

Kagramanova A.V., Knyazev O.V., Parfenov A.I.


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.

Terapevticheskii arkhiv. 2023;95(2):193-197
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