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Issue. Articles

¹4(90) // 2016

 

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1. Original researches

 


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The effects of body weight and concomitant pathology of the biliary tract on the onset and progression of lipid abnormalities in patients with nonalcoholic fatty liver disease in combination with obesity

Yu. M. Stepanov1, A. Yu. Filippova2

1 SI «Institute of Gastroenterology of NAMS of Ukraine», Dnipro
2 SE «Dnipropetrovsk medical academy of Health Ministry of Ukraine», Dnipro

Objective — to study the characteristics of blood lipid spectrum and the main phenotypes of dyslipidemia (DL), depending on the body weight and concomitant diseases of the biliary tract (BT) in patients with non-alcoholic steatohepatitis (NASH) in conjunction with obesity.
Materials and methods. The study involved 100 patients (19 men and 81 women) with NASH in combination with obesity and BT pathology, who at the time of sonographic and morphological study of liver biopsy revealed signs of hepatic steatosis. Themean age of patients was 53.82 ± 1.12 years. The control group consisted of 20 healthy persons. Depending on the degree of increase in body mass index (BMI), all patients with NASH were divided into three groups: group 1 included subjects with BMI of 25 — 29.9 kg/m2 (overweight); group 2 consisted of patients with a BMI 30 — 34.9 kg/m2 (obesity I degree); group 3 with a BMI 35- 39.9 kg/m2 (obesity II degree). Depending on the BT pathology, the patients were divided into 3 groups: NASH with chronic non-calculous cholecystitis; NASH with chronic calculous cholecystitis; NASH in patients after laparoscopic cholecystectomy (LCE) with concomitant post-cholecystectomic syndrome (PHES). The determine the lipid exchange characteristics, total cholesterol (TCHOL), total lipids (TL), triglycerides (TG), low density lipoproteins ­(LDL-CHOL), high density lipoproteins (HDL-CHOL) were measured. The DL phenotype was determined by the classification D. S. Fredrickson with recent addenda.
Results. For all NASH patients, the lipid exchange disorder were typical in comparison with the healthy controls: as regards the levels TCHOL, TG, TL, LDL-CHOL) (p < 0.05; p < 0.001). The highest indices of TCHOL, TG, TL, ­LDL-CHOL were revealed in NASH patients combined with obesity I degree (p < 0.001) and obesity II degree (p < 0.001), and the lowest indices of lipid profile were revealed at th overweight (p < 0.05; p < 0.001). The BT comorbidities partially affected the lipid profile indicators. Thus, with NASH HDL-CHOL in patients with concomitant PHES was at normal values, as compared with a low level of HDL-CHOL in patients with chronic non-calculous and calculous cholecystitis, which may indicate a lesser severity of inflammation in the BT after LCE and further can reduce atherogenic LDL-CHOL fractions.
Conclusions. The progression of intensity of the lipid imbalance in NASH patients in combination with obesity and biliary tract pathology significantly depends on the BMI parameters and partially (as relates to some lipid spectrum indices) depends on the presence of concomitant biliary tract pathology. Two main phenotypes DL IIa and IIb have been determined, and their comparison with the nosology and disease stage made it possible to consider them as the main phenotypes, specific for the investigated comorbidity.

Keywords: non-alcoholic steatohepatitis, obesity, biliary tract, lipid metabolism, body mass index.

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Original language: Ukrainian

2. Original researches

 


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Pathomorphological changes of esophageal mucosa in patients with combination of gastroesophageal reflux disease and arterial hypertension

O. Ye. Gridnyev

SI «L. T. Mala National Therapy Institute of NAMS of Ukraine», Kharkiv

Objective — to evaluate histological lesions of the esophageal mucosa in patients with gastroesophageal reflux disease in combination with arterial hypertension.
Materials and methods. The study included 89 patients with gastroesophageal reflux disease and 126 patients with GERD in combination with arterial hypertension, mean age was (41.99 ± 1.57) and (55.92 ± 0.91) years, respectively. The histological investigations were performed on the biopsies, obtained at the video-endoscopy of the distal esophageal mucosa. The specimens were stained with hematoxylin and eosin. The investigations were performed on the mucosa specimens from the esophagus with esophagitis signs and compared them with the intact esophageal mucosa. The normal esophageal epithelium (control group) was defined as the absence of visible erosions at endoscopy and no basal cell hyperplasia, elongated papillae or cellular infiltrates on histological examination.
Results. The frequency of erosive reflux esophagitis in patients with comorbidity is higher than in patients with isolated gastroesophageal reflux disease (p < 0.05). Both groups were characterized by basal cell hyperplasia, elongation of the lamina propria papillae with vascular congestion, dilated intercellular spaces, focal or diffuse infiltration of the epithelium by polymorphonuclear leucocytes, and manifested hyperkeratosis, proliferation of basal cells and acanthosis. This change could represent a mucosal reaction towards recovery of the epithelial barrier. Morphometric study revealed a significant increase in the thickness of the basal layer of the epithelium and the papillae height both at isolated GERD, and at comorbidity compared to control (p < 0.05). Increasing in the basal layer of the esophageal mucosa epithelium thickness is less pronounced in comorbid patients compared with isolated pathology. Hyperplasia of the basal layer of the epithelium, the elongation of papillae, parakeratosis, acanthosis and neutrophilic infiltration found in both groups, with almost the same frequency. Vascular lesions (irregular hypertrophy of the muscular layer, focal sclerosis, hyalinosis and narrowing of the arteries), ectasia of venules, formation of perivascular hemorrhage; swelling and degeneration of the epithelium are more prevalent in the mucosa of comorbid patients compared to isolated gastroesophageal reflux disease (p < 0.05).
Conclusions. Combination of GERD and arterial hypertension resulted in the morphological and histological disorders in the esophageal mucosa, that may be associated with the pathogenetical causes of arterial hypertension, hypoxia and endothelial dysfunction.

Keywords: gastroesophageal reflux disease, arterial hypertension, esophageal mucosa, histological and morphometric analysis.

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Original language: Russian

3. Original researches

 


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Indexes of lipid metabolism in patients with acute edematous pancreatitis depending on the genes IL-4 (C-590T), TNF-α (G-308A), PRSS1 (R122H), SPINK1 (N34S) and CFTR (delF508C) polymorphism

S. I. Ivashchuk, L. P. Sydorchuk

Bukovinian State Medical University, Chernivtsi

Objective — to study some indexes of the lipid metabolism in patients with acute edematous pancreatitis depending on the genes IL-4 (C-590T), TNF-α (G-308A), PRSS1 (R122H), SPINK1 (N34S) and CFTR (delF508C) polymorphisms.
Materials and methods. Genetic studies have been performed for 123 patients with edematous pancreatitis, among whom were 23 (18.7 %) women and 100 (81.3 %) men. The control group consisted of 40 healthy age- and gender-matched subjects. Gene PRSS1 (R122H) was investigated in 123 patients, CFTR (delF508) and IL-4 (C-590T) — in 101, SPINK1 (N34S) — in 63, TNF-α (G-308A) — in 11. Genes polymorphism was studied with the method of PCR using oligonucleotide primers company Metabion (Germany). The research of the lipids included the determination of the levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and Apolipoprotein (Apo) B using the reagents of the firm «Thermo Fisher Scientific» (Finland), and calculation atherogenic index (AI).
Results. À pronounced dyslipidemia was revealed in the most part of patients. In NN genotype carriers of the gene CFTR (delF508) higher levels of TC, HDL-C and LDL-C were determined, while NM genotype carriers had the highest levels of TG, Apo B and AI. In the GG genotype carriers of the gene PRSS1 (R122H) significantly increased indexes of the TC, HDL-C, LDL-C and uncertain — TG, Apo B and AI. In the TT-genotype carriers of the gene IL-4 (C-590T) were observed higher levels of TC, HDL-C and LDL-C, while in the owners of the C-allele — higher content of TG, Apo B and AI. By GG genotype of the gene TNF-α (G-308A) were higher levels of TC, HDL-C and LDL-C compared with GA-genotype carriers in which have been higher TG, Apo B and AI.
Conclusions. The course of edematous pancreatitis was accompanied by significant dyslipidemic changes that had no clear correlation with the polymorphic variants of the gene CFTR (delF508) (hypercholesterolemia in the NN-genotype owners, hypertriglyceridemia — in NM carriers) gene PRSS1 (R122H) (more significant hypercholesterolemia in patients with GG-genotype, p < 0.01), IL-4 gene (C-590T) (increase of the TC by LDL-C in the TT-genotype owners) and TNF-α (G-308A) (hypercholesterolemia in GG- carriers hypertriglyceridemia — in persons with GA-variant).

Keywords: pancreatitis, polymorphism, lipids, gene, CFTR (delF508), PRSS1 (R122H), IL-4 (C-590T), TNF-α (G-308A).

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Original language: Ukrainian

4. MEDICINES

 


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Dysbiosis and bacterial overgrowth syndrome at the irritable bowel syndrome: correction with the use of Saccharomyces boulardii CNCM I -745

S. M. Tkach1, À. Å. Dorofeev2, Ì. Ì. Rudenko2

1 Ukrainian Research and Practical Centre of Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of the Ministry of Health of Ukrainå, Kyiv
2 O. O. Bogomolets National Medical University, Kyiv

The article presents data on the intestinal microbiota in the norm and at the irritable bowel syndrome (IBS). Modern approaches have been considered to the investigation of the role of intestinal microbiota at IBS, and clinical recommendation given for the module correction of intestinal microbiota at IBS, in particular with the use of antibiotics, probiotics and prebiotics. The results of own investigation have been presented, that showed the high clinical and microbiological efficacy of the probiotic, containing Saccharomyces boulardii CNCM I-745, in the IBS treatment.

Keywords: irritable bowel syndrome, intestinal dysbiosis, bacterial overgrowth syndrome, probiotics, Saccharomyces boulardii CNCM I-745.

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Original language: Russian

5. MEDICINES

 


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The choice of the treatment strategy of patients risk of the upper gastrointestinal bleedings

G. D. Fadieienko, T. A. Solomentseva

SI «L. T. Mala National Therapy Institute of NAMS of Ukraine», Kharkiv

Acute gastrointestinal bleeding (ÀGIB) is a dangerous complication of the peptic ulcer disease and non steroidal anti-inflammatory drug-associated gastro pathology. The clinical picture depends on the intensity of bleeding and accompanying pathology. The main ÀGIB reasons are peptic ulcers, Mallory-Weiss lesions, erosive gastritis, reflux esophagitis. The diagnosis and optimal treatment requires the risk stratification. Endoscopy gives the possibility of not only reveal the localization of the bleeding site, but also to use a variety of therapeutic measures, such as injection therapy and thermoscoagulation. Therapy with proton pump inhibitors contributes to the acid suppression, being highly effective at ÀGIB. The patients with peptic ulcer and chronic gastritis should undergo H. pylori tests, and in case of the infection exposure, should be administered. Patients under ÀGIB risk have to discontinue NSAID therapy whenever possible. If not, then cyclooxygenase-2 inhibitors in combination of PPIs must be the therapy of choice. Such a technique is aasociated with the lowest bleeding risk, however the incidence of the cardiovascular events can be increased, this the choice of therapy must be performed on the individual basis.

Keywords: ulcers, gastrointestinal bleeding, Helicobacter pylori, NSAID-associated gastropathy, proton pump inhibitors, omeprazole, Îmez.

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Original language: Russian

6. MEDICINES

 


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Rabeprazole: the news about the famous

N. V. Bezd³tko

National University of Pharmacy, Kharkiv

Proton pump inhibitors are the drugs of choice for the treatment of acid-related diseases. Rabeprazole is a drug with strong evidence-based effectiveness and safety, but its therapeutic potential is not adequately appreciated by the Ukrainian clinicians. The paper presents a review of the literature, including a detailed description of the peculiarities of rabeprazole pharmacological properties, its clinical efficacy and safety in comparison with other proton pump inhibitors. Special attention is paid to the differences of mainly non-enzymatic metabolism of rabeprazole, and hence it’s low potential for the inter-medication interactions. The information has been presented as regards its gastroprotective properties and other pleiotropic effects on the upper gastrointestinal motility, the direct anti-helicobacter effect. The detailed characteristics have been given for the rabeprazole preparation Rabimak (MacLeods Pharmaceuticals), which meets the modern requirements to the generic drugs.

Keywords: acid-dependent diseases, treatment, proton pump inhibitor, rabeprazole.

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Original language: Russian

7. MEDICINES

 


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Pantoprazole: peculiarities of pharmacokinetics, acid-inhibiting actions, clinical efficacy and safety

V. Ì. Chernobrovyy, O. Î. Ksenchón

National Pirogov Memorial Medical University, Vinnytsya

The article present literature review and results of own investigations (50 patients with acid-related peptic esophago-gastroduodenal diseases) with the use of gastric ðÍ-monitoring to assess acid-inhibiting actions of pantoprazole (Zolopent), pharmacokinetics, clinical efficacy and safety of its use in comparison with omeprazole, lansoprazole and omeprazole. Based on own data, the acid-inhibiting pantoprazole action exceeds that of omeprazole, lansoprazole and esomeprazole. acid-inhibiting ðantoprazole action depends not only on the peculiarities of its acting substance, but from other factors (bio availability, clinical group of the investigated subjects: healthy volunteers, patients with gastroesophageal disease, H. pylori infection, pharmacokinetics of the enzymes of cytochrome Ð450 system with presence of the ethnic-dependent metabolism type from rapid to slow etc.). The clinical efficacy and safety profile of pantoprazole meets the modern standards of treatment of acid-related peptic esophago-gastroduodenal diseases, including disorders associated with H. pylori eradication. The considerable ðantoprazole advantage over other PPIs lays in the possibility of its use in the complex therapy, for example in geriatric cardiology. Pantoprazole in combination with clopidogrel, in contrast to îmeprazole, doesn’t threaten drugs interactions with slowdown of anti-aggregate action of clopidogrel resulting from the low Pantoprazole affinity to the enzymes of cytochrome Ð450 system.

Keywords: pantoprazole, pharmacokinetics, acid-inhibiting action, êëèíè÷åñêàÿ clinical efficacy, safety profile.

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Original language: Ukrainian

8. MEDICINES

 


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Influence of L-arginine and betaine on structural and functional state of erythrocytes, lipids and homocysteine blood levels in patients with nonalcoholic steatohepatitis

V. V. Kharchenko

P. L. Shupyk National Medical Academy îf Postgraduate Education, Kyiv

Objective — to study Betargin effects on the structural and functional state of erythrocytes, lipids and homocysteine  blood levels in patients with nonalcoholic steatohepatitis (NASH).
Materials and methods. Investigation involved 50 patients with NASH against the background of abdominal syndrome, from them 29 (58 %) women, and 21 (42 %) men with the mean age 38 to 60 years. Anthropometric, clinical laboratory, biochemical studies, ultrasound of the abdominal cavity have been conducted.
Results. The following changes of structural and functional state of erythrocytes were revealed before the treatment in patients with NASH: reduction of the deformation index, aggregation index, relative contact hemolysis, intensity of red blood cells and glucose utilization, the decrease of the in erythrocyte ATP levels and erythrocytes resistance to the peroxidation, and increase of the relative viscosity of erythrocyte suspension (p < 0.001), indicating the microcirculatory disorders. After the treatment, patients of the main group demonstrated considerable improvement of the structural and functional erythrocytes’ status. Thus, one of the most important indicators deformation index, characterizing the ability of erythrocytes to change their form with the purpose of oxygen transport to the terminal parts of the microvasculature, increased in 1.7 times in patients of the main group after 4 months of treatment (p < 0.001). Treatment with the Betargin contributed to the improvement of structural and functional indicators of erythrocytes. The relative viscosity of erythrocyte suspension reduced in 2.1 times, aggregation index increased in 1.9 times, the relative contact hemolysis increased in 1.6 times, ATP in 1.9 times. Moreover, the intensity of glucose metabolism in erythrocytes and resistance to the peroxidation increased (ð < 0.001), and positive dynamics of the blood lipid spectrum enhanced (ð < 0.001).
Conclusions. The study revealed positive effects of Betargin on the lipid metabolism, homocysteine  blood levels, as well as on the structural-functional state of erythrocytes.

Keywords: Betargin, L-arginine, betaine, nonalcoholic steatohepatitis, erythrocyte, lipids, homocysteine.

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Original language: Ukrainian

9. MEDICINES

 


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The use of L-glutathione for the pathogenetic protection of stomach and liver in patients with type 2 diabetes mellitus

M. B. Shcherbinina1, N. M. Palibroda2, M. V. Patratii2,
A. V. Zakrevska3, G. S. Korolenko4

1 Oles Íonchar Dnipropetrovsk National University, Dniprî
2 Bukovinian State Medical University, Chernivtsi
3 Dniprî Municipal Polyclinics ¹ 4
4 Dnipropetrovsk Medical Academy, Dniprî

Objective — to evaluate effects of Hepaval (L-glutathione) on the state of gastric mucosa and course of non-alcoholic steatohepatitis (NASH) after Helicobacter pylori eradication in patients with type 2diabetes mellitus (DM 2).
Materials and methods. This open comparative study included 84 patients with DM 2 (39 men and 45 women) with a mean age of 53.8 ± 7.6 years. Rapid urease test and a stool antigen test were used to determine H. pylori infection in each patient. Quadruple therapy was administered for 14 days. After eradication therapy, patients were randomized into two groups, each of42 patients: subjects from the main group received Hepaval 2 caps. twice a day in addition to basic therapy (basic group 1) for six weeks, while 42 patients received only basic therapy (comparative group 2).
The upper endoscopy, morphological study of gastric biopsy specimens (semiquantitative evaluation of composition and degree of infiltration of gastric mucosa, the total volume density of the microvasculature); liver sonographic parameters (size, degree of steatosis) and the degree of liver fibrosis, according to RTE-elastography; liver enzymes were evaluated before and after the treatment period.
Results. In both groups, the successful eradication of H. pylori resulted in the reduction of inflammation endoscopic signs, the healing stomach and duodenal ulcers, the epithelialization of gastroduodenal erosions, accompanied with improved histology of gastric mucosa, reduction of gastritis activity degree. With this, patients of the maingroup 1, administered Hepaval, demonstratedmore significant improvement, while dysmotility of upper gastrointestinal tract and gastroduodenal mucosal defects were revealed in patients from comparison group. In both groups, significant (p < 0.001) reduction in inflammatory cell infiltration was found. However, these indices were significantly better (p < 0.05) in the main group, while in comparison group 2 more significant inflammatory infiltration of gastric mucosa, degenerative and necrotic changes in epithelial cells with the presence of multiple cases of gastroduodenal erosions were still present after the bacteria elimination. The manifestations of atrophic changes of the stomach mucosa, intestinal metaplasia, microvasculature condition, hepatomegaly, steatosis (1 — 2 degree), fibrosis (F0-F2) were not statistically different before and after treatment. At the same time, the normalization of transaminases was indicated in the main group 1 after 6 week treatment with Hepaval. In the comparison group 2, serum aminotransferase levels were not statistically different at the end of treatment period and significantly (p < 0.05) differed from group 1 patients.
Conclusions. Based on the data of endoscopy and morphological studies, Hepaval (L-glutathione) contributed to more rapid recovery of the natural state of gastroduodenal mucosa during regression of Helicobacter pylori-induced gastritis. The inclusion of Hepaval in the basic therapy resulted in the fast normalization of liver enzymes at NASH. Hepaval did not cause seriousside effects, requiring drug discontinuation, and was well tolerated. The additional Hepaval (L-glutathione) inclusionin the complex therapy of patients with type 2 DM is pathogeneticallyjustifiedby its effects in eliminating metabolic disorders in gastroduodenal mucosa and liver.

Keywords: diabetes mellitus type 2, non-alcoholic fatty liver disease, steatohepatitis, Hepaval, L-glutathione, gastroduodenal mucosa.

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Original language: Ukrainian

10. MEDICINES

 


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Sofosbuvir in the treatment of chronic viral hepatitis C: facts and expectations

O. V. Kolesnikova

SI «L.T. Mala National Therapy Institute of NAMS of Ukraine», Kharkiv

The modern schemes without oral interferon provide the achievement of sustained virological response (SVR) in 90 % of cases, and can reduce the duration of treatment to 12 weeks for the majority of patients with chronic hepatitis C, for both non-treated and treated patients. A plenty of combinations of antiviral drugs with the direct action exist, that can help achieving the optimal balance of the therapeutic efficacy and safety. Each of these schemes can be modified according to different parameters. The application of combinations based on sofosbuvir is advisable for patients, infected with hepatitis C virus (HCV) of 1 — 6 genotypes. Its efficacy, confirmed in the clinical trials, was combined with the high safety profile, it resulted in the shortening of treatment duration and achieving of patients’ recovery.

Keywords: chronic viral hepatitis C, sustained virological response, sofosbuvir, efficiency, safety.

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Original language: Russian

11. Reviews

 


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Therapeutic treatment strategies of ulcerative colitis: realities and future

I. E. Kushnir

SI «L.T. Mala National Therapy Institute of NAMS of Ukraine», Kharkiv

Ulcerative colitis (UC) represents a widespread disease. The article deals with the modern methods of UC treatment with the use of aminosalicylates, corticosteroids, immunosuppressive drugs and biological therapy, but most of the standard therapeutic approaches to the treatment of patients with UC are ineffective. The author present data from controlled trials of safety and efficacy of new bioactive molecules (adhesion molecules inhibitors,anti-cytokines, immunosuppressive agents) in the treatment of refractory forms of disease.

Keywords: ulcerative colitis, treatment, aminosalicylates, corticosteroids, immunosuppressive, tumour necrosis factor alpha monoclonal antibody, adhesion molecules inhibitors.

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Original language: Russian

12. CLINICAL CASE

 


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Clinical application of the proton pump inhibitors in the treatment of gastroesophageal reflux disease (cases from clinical practice)

O. O. Bondarenko1, Î. Ì. Agibalov2

1 Danylo Halytskiy Lviv National Medical University
2 Multispecialty Hospital Vitacenter, Zaporizhzhya

The article presents consideration of the peculiarities of the atypical forms of GERD course. For the primary differential diagnosis patients with bronchopulmonary symptoms, the use of two-week test with proton pump inhibitors (nolpaza 40mg) is recommended. In the case of chest pain, further patient’s examination is advisable to exclude the coronary disease. For the patients with refractory GERD, triple the dose of PPIs is proposed together with replacement of the former drug by another one with a different type of metabolism. Theseclinical examples allow us to recommend an individualized approach to the treatment of the atypical and refractory forms of GERD.

Keywords: atypical and refractory forms of the gastroesophageal reflux disease, clinics, diagnosis, treatment, proton pump inhibitors.

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Original language: Russian

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