Gastritis and duodenitis: clinical guidelines

List of Abbreviations

CI – confidence interval

PPI – proton pump inhibitors

H. pylori – Helicobacter pylori

NSAIDs – non-steroidal anti-inflammatory and antirheumatic drugs

RR – relative risk

OR – odds ratio

EGD – esophagogastroduodenoscopy

FD – functional dyspepsia

Terms and Definitions

Gastritis is an inflammatory disease of the gastric mucosa.

Chronic gastritis – a group of chronic disorders characterized by persistent inflammatory infiltration and impaired cell renewal, with the development of intestinal metaplasia and atrophy in the gastric mucosa.

Helicobacter pylori (H. pylori) is a spiral-shaped Gram-negative bacterium capable of colonizing the gastric mucosa and causing inflammation.

Eradication – treatment aimed at eliminating Helicobacter pylori (H. pylori) infection.

First-line eradication regimen – an H. pylori eradication regimen prescribed as the initial treatment.

Second-line eradication regimen – an eradication regimen prescribed when the first-line regimen fails.

Autoimmune gastritis – an organ-specific autoimmune disease characterized by the presence of antibodies against gastric parietal cells and/or intrinsic factor.

Chronic duodenitis – a group of chronic disorders characterized by inflammatory infiltration of the duodenal mucosa, gastric epithelial metaplasia, and histoarchitectural abnormalities such as villous shortening and crypt deepening.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Gastritis – an inflammatory disease of the gastric mucosa. Acute and chronic gastritis are distinguished. Chronic gastritis – a group of chronic disorders characterized by persistent inflammatory infiltration and impaired cell renewal, with the development of intestinal metaplasia and atrophy in the gastric mucosa.

Chronic duodenitis is characterized by inflammatory infiltration of the duodenal mucosa, gastric epithelial metaplasia, and histoarchitectural abnormalities such as villous shortening and crypt deepening.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Gastritic changes represent reactions of the gastric mucosa in response to various endogenous and exogenous pathogenic factors. The main changes that make up the morphological picture of chronic gastritis include inflammation, atrophy, impaired cell renewal (including metaplasia and dysplasia).

The bacterium Helicobacter pylori, which colonizes the gastric mucosa, serves as one of the leading etiological factors of gastritis. Establishing the etiological role of H.pylori has made chronic gastritis a clearly defined and clinically significant nosological entity—a disease with a known cause, stages of pathogenetic development, a defined prognosis, and, finally, has determined the possibilities of etiotropic treatment. B. J. Marshall and J. R. Warren, who first succeeded in isolating a culture of a previously unknown gram-negative microorganism from human gastric biopsies, already in the first publication that initiated large-scale study H.pylori, linked the presence of this bacterium with infiltration of the epithelium and lamina propria by polymorphonuclear leukocytes against the background of lymphoplasmacytic infiltration [1]. The ability of H.pylori to colonize the gastric mucosa and cause acute and subsequently chronic gastritis was confirmed in self-inoculation experiments independently conducted by B. Marshall (1985) and A. Morris (1987). Of great importance for studying the pathogenetic significance of H.pylori are animal experiments: models in which Helicobacter-induced gastritis and some other H.pylori-associated diseases can be reproduced include mice, Mongolian gerbils, guinea pigs, gnotobiotic piglets, and primates [2]. The Mongolian gerbil model reproduces the gastric carcinogenesis paradigm (Correa cascade): chronic inflammation caused byH. pylori, intestinal metaplasia, atrophy, dysplasia/intraepithelial neoplasia, and invasive adenocarcinoma. Various authors have succeeded in reproducing gastritis in humans after inoculating volunteers with a culture of H.pylori [2, 3].

A number of factors ensure mucosal colonization and survival of H. pylori in the unique gastric environment. Urease, an enzyme that hydrolyzes urea to produce ammonia and carbon dioxide, is important for neutralizing acid in the microorganism's microenvironment. Flagella allow the bacterium to "target" its movement within the mucus layer above the epithelium. Other bacterial enzymes can degrade mucin. About 10% of H. pylori are in direct contact with the epithelium. Adhesion of H. pylori to epithelial cells is a complex process involving a number of surface proteins. For example, BabA (blood group antigen binding adhesin) is an adhesin that binds to Le^b blood group antigens on epithelial cells; the gene allele for this adhesin – babA2 – is closely associated with the development of peptic ulcer disease and gastric cancer in certain populations [2, 4].

The bacterial genome contains the cag PAI pathogenicity island, marked by the cagA gene ("cytotoxin-associated gene A"). This gene is found in 50–70% of H. pylori strains. Some proteins encoded by cag PAI are used to build the bacterium's type IV secretion system, through which H. pylori, upon attaching to a gastric epithelial cell, injects CagA, peptidoglycan, and possibly other of its own molecules into the host cell. H. pylori proteins inside the epithelial cell "trigger" several signaling pathways, resulting in changes to the host cell cytoskeleton, disruption of intercellular junctions, altered proliferation and apoptosis, and a pro-inflammatory effect. Gastric epithelial cells respond to the presence of H. pylori by releasing IL-8 and RANTES (regulated upon activation, normal T cell expressed and secreted), leading to an active inflammatory response in the mucosa. About 50% of H. pylori strains secrete a highly immunogenic protein – vacuolating cytotoxin A (VacA), which causes cell vacuolization in vitro, while in vivo it is linked to inflammation and apoptosis [2, 4]. Thus, H. pylori colonization maintains the persistence of the inflammatory infiltrate in the gastric mucosa. H. pylori-induced inflammation leads to atrophy – the irreversible loss of gastric glands replaced by fibrous tissue or metaplastic epithelium. Atrophic gastritis, especially involving the gastric body and accompanied by hypochlorhydria, is a proven risk factor for gastric adenocarcinoma [2, 5, 6, 7, 8, 9].

Pathomorphological data, as well as studies using the sucrose permeability test, demonstrate that in gastritis and functional dyspepsia, there is an increased epithelial permeability syndrome, the severity of which correlates with the activity of the inflammatory process in the gastric mucosa. H. pylori contributes to the development of this syndrome by exerting a negative effect on the structural components of epithelial tight junctions [10]. Thus, increased epithelial permeability syndrome is involved in the pathogenesis of gastritis, and drug therapy with a cytoprotective effect is pathogenetically justified [10].

Autoimmune gastritis is based on autoimmune mechanisms, which is confirmed by the presence of antibodies against parietal cell antigens and/or intrinsic factor, as well as the combination of gastritis with other autoimmune diseases (autoimmune thyroiditis, type 1 diabetes mellitus, vitiligo, etc.) [11, 12, 13].

Other specific forms of gastritis are less common, characterized by specific etiological factors, or may accompany other diseases. Lymphocytic gastritis may be associated with celiac disease, eosinophilic gastritis occurs within the framework of eosinophilic gastroenteritis, and granulomatous gastritis is associated with Crohn's disease, sarcoidosis, and vasculitis [7].

1.3 Epidemiology of the Disease or Condition

According to the statistical materials "Morbidity of the adult population of Russia in 2019," more than 538,000 adults were registered with a newly diagnosed condition of "gastritis and duodenitis," and the adult incidence rate was 462.0 per 100,000. In total, based on adult healthcare utilization in 2019, more than 700,000 cases with a diagnosis of "gastritis and duodenitis" were registered. Thus, the diagnosis of "gastritis" is widely used in clinical practice. On the one hand, this fact reflects the high real frequency of the disease, but on the other hand, it demonstrates subjective and objective difficulties both in interpreting dyspepsia symptoms and in accessing necessary diagnostic methods—primarily high-definition video endoscopy with electronic/virtual chromoendoscopy and magnification, as well as pathomorphological examination of gastric mucosal biopsies.

The high prevalence of H. pylori in the population determines the high frequency of chronic gastritis. According to major epidemiological studies conducted between 2004 and 2012 in various regions of the Russian Federation, H. pylori infection was detected in 65–92% of adults [9]. Studies conducted in recent years in the Russian Federation have demonstrated a downward trend in the proportion of infected individuals in the population. The prevalence of H. pylori according to the ¹³C-urea breath test in individuals without prior eradication therapy (n=19,875) was 38.8% (41.8% in 2017, 36.4% in 2019, p < 0.0001) [14].

1.4 Features of Coding the Disease or Condition

Gastritis and duodenitis (K29)

K29.0 - Acute hemorrhagic gastritis

Acute (erosive) gastritis with hemorrhage

K29.1 - Other acute gastritis

K29.2 - Alcoholic gastritis

K29.3 - Chronic superficial gastritis

K29.4 - Chronic atrophic gastritis

Mucosal atrophy

K29.5 - Chronic gastritis, unspecified

Chronic gastritis:

· antral

· fundic

K29.6 - Other gastritis

Giant hypertrophic gastritis

Granulomatous gastritis

Menetrier's disease

K29.7 - Gastritis, unspecified

K29.8 - Duodenitis

K29.9 - Gastroduodenitis, unspecified

K31.8 - Other specified diseases of stomach and duodenum

1.5 Classification of the disease or condition

The Kyoto Consensus report proposed a classification for chronic gastritis based on an etiological principle [7]:

Autoimmune gastritis

Infectious gastritis

- Gastritis caused by Helicobacter pylori

- Bacterial gastritis (Helicobacter heilmannii, Enterococcus, Mycobacteria, secondary syphilitic gastritis)

- Gastric phlegmon

- Viral gastritis (enterovirus, cytomegalovirus, Epstein-Barr virus)

- Mycotic gastritis (mucormycosis, candidiasis, histoplasmosis)

- Parasitic gastritis (Cryptosporidium, Strongyloides stercoralis)

Gastritis caused by external agents

- Medication-induced gastritis

- Alcoholic gastritis

- Radiation-induced gastritis

- Chemical gastritis

- Biliary reflux-induced gastritis

- Gastritis caused by other specified external agents

Gastritis of specific types

- Lymphocytic gastritis

- Ménétrier's disease

- Allergic gastritis

- Eosinophilic gastritis

Gastritis associated with other classified diseases

- in sarcoidosis

- in vasculitis

- in Crohn's disease.

The Sydney system of chronic gastritis classification (1990), modified in Houston in 1994, takes into account the topography of the lesion (gastric body, antrum) and morphological changes in the gastric mucosa (degree of inflammation activity, severity of inflammation, severity of atrophy and metaplasia, presence and degree of H. pylori colonization). These characteristics are assessed using a visual analogue scale semiquantitatively according to the severity of the morphological feature: normal (feature absent), mild, moderate, severe. The use of the visual analogue scale has reduced subjectivity in describing the histological picture [15]. The topography and histological characteristics of gastritis are important because the gastritis phenotype determines the risk of developing conditions such as duodenal ulcer, gastric ulcer, and gastric cancer [2, 4, 6, 7, 9].

The stage and grade of atrophic gastritis and intestinal metaplasia (metaplastic atrophy) serve as indicators of the risk of gastric cancer development [16-18]. To facilitate and, where possible, standardize the prognosis of chronic gastritis—primarily the assessment of gastric cancer risk—several methods are used. The OLGA (Operative Link for Gastritis Assessment) prognostic system utilizes the visual analogue scale of the Sydney classification. To determine the stage of gastritis, the histological severity of atrophy is correlated with its topography: stage 0 indicates a minimal risk of carcinogenesis, whereas stage IV, respectively, indicates a maximum risk, which is 5–6 times higher than the population risk of gastric cancer [19, 20]. The Russian revision of the OLGA system significantly simplifies the assessment of gastric mucosal atrophy (metaplastic atrophy) through visualization using pictograms. The Russian revision of the OLGA system was approved by the III Congress of the Russian Society of Pathologists and approved by the Federal Service for Surveillance in Healthcare and Social Development (FS No. 2010/220 dated June 10, 2010) [21]. The OLGIM system, which is based on similar core principles, analyzes intestinal metaplasia instead of atrophy [22].

Endoscopic assessment of the extent of gastric mucosal atrophy according to Kimura-Takemoto [23, 24] or the modified EGA scale [25], as well as endoscopic assessment of the severity of intestinal metaplasia according to the EGGIM scale [26], is becoming increasingly widespread.

The presence of acute and/or chronic erosions of the stomach and duodenum should be indicated in the endoscopic report or clinical diagnosis as a separate item. The natural history and clinical significance of erosive gastritis or erosive duodenitis depend on the etiology. Frequent causes include nonsteroidal anti-inflammatory drugs (NSAIDs), stress, and alcohol consumption. Rarer causes include radiation injury, viral infection (e.g., cytomegalovirus), and direct trauma (e.g., nasogastric tube) [7, 27].

1.6 Clinical presentation of the disease or condition

Dyspepsia is defined as symptoms such as epigastric pain or burning, epigastric fullness, and early satiety. Chronic gastritis, which is characterized by specific morphological changes in the mucosa, is often not the cause of symptoms, including dyspeptic symptoms. However, in a subset of patients with dyspepsia, the presenting clinical symptoms may be caused by chronic H. pylori-associated gastritis, as evidenced by their sustained resolution following eradication of the infection. H. pylori- and chronic gastritis-associated dyspepsia was proposed by the Kyoto Consensus report to be considered as a separate clinical entity. Conversely, the persistence of dyspeptic symptoms despite successful H. pylori eradication is considered a manifestation of a functional disorder—functional dyspepsia [6, 7, 9].

Gastroduodenal erosions, including those caused by NSAID use, are frequently paucisymptomatic and may present with acute upper gastrointestinal bleeding [7, 29].

The clinical presentation of autoimmune gastritis is typically associated with manifestations of vitamin B12 deficiency (macrocytic anemia, neurological symptoms), iron deficiency anemia, and concomitant autoimmune diseases [11-13]. However, some studies suggest the presence of gastroenterological symptoms in patients with autoimmune gastritis. Gastroenterological symptoms were recorded in 60% of patients with autoimmune gastritis, presenting predominantly as dyspeptic symptoms, which were more frequently observed in patients younger than 55 years, non-smokers, and those without anemia [29]. In another study, epigastric pain was identified in 35% of autoimmune gastritis cases, nausea in 22%, early satiety in 10%, and postprandial fullness in 7.1%. Frequent symptoms included heartburn (24%) and regurgitation (12%) [30]. Using pH-impedance monitoring in autoimmune gastritis, it has been shown that non-acid refluxes can be associated with symptom presentation [31].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing the diagnosis of the disease/condition:

The diagnosis of gastritis is based on the histological detection of gastric mucosal inflammation (neutrophilic leukocytes in the lamina propria and intraepithelial, density of mononuclear inflammatory infiltrate), as well as atrophy and intestinal metaplasia.

Modern methods of endoscopic examination, in particular high-definition video endoscopy with multimodal imaging and magnification, provide additional highly informative capabilities for diagnosing gastritis, duodenitis, and precancerous changes of the gastric mucosa.

H. pylori infection is the most important etiological factor of gastritis, and positive H. pylori tests indicate the presence of chronic gastritis.

2.1 Complaints and Anamnesis

Potential symptoms in patients with gastritis and the interpretation of these symptoms are presented in subsection 1.6.

When taking the medical history, it should be clarified whether the patient has previously undergone EGD with biopsy; whether there were indications of precancerous conditions and changes in the gastric mucosa (atrophy, intestinal metaplasia, epithelial dysplasia). To assess the prognosis, it is important to clarify whether eradication therapy for H. pylori infection was previously performed, which treatment regimen was used, and whether the efficacy of anti-Helicobacter therapy was verified.

For autoimmune gastritis, a history of vitamin B12 deficiency and macrocytic anemia is important, as well as the presence of autoimmune diseases such as autoimmune thyroiditis, type 1 diabetes mellitus, vitiligo, etc., and gastric body mucosal atrophy with a relatively preserved antral mucosa revealed by prior endoscopic and pathomorphological examination.

2.2 Physical Examination

Physical examination generally reveals no findings specific to gastritis.

2.3 Laboratory Diagnostics

• All patients with gastritis are recommended to undergo a complete blood count with determination of hemoglobin levels, hematocrit, erythrocyte volume, and color index in order to rule out anemia resulting from bleeding due to erosive gastroduodenal mucosal lesions or autoimmune gastritis [30, 32-34].

LeRR CLoE 4Level of recommendation confidence C (level of evidence – 4)

Comments: The complete blood count in chronic gastritis most often remains unchanged, but anemia may be detected—either microcytic, indicating overt or occult bleeding or impaired iron absorption, or macrocytic due to vitamin B12 deficiency in autoimmune gastric involvement [30, 32-34].

• All patients with suspected autoimmune gastritis are recommended to undergo blood tests for antiparietal cell antibodies and anti-intrinsic factor antibodies [11-13, 34, 35, 36].

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

Comments: The target of anti-parietal cell antibodies is the H+/K+ ATPase (alpha and beta subunits of the proton pump). They are detected in 85-90% of patients with pernicious anemia. The sensitivity for the diagnosis of autoimmune gastritis is ~80%, with low specificity (they are found in individuals without autoimmune gastritis). Antibodies to intrinsic factor block the binding of cobalamin to intrinsic factor. The sensitivity for diagnosing autoimmune gastritis is ~50%, but specificity reaches 99% [11-13, 34, 35, 36].

• All patients with suspected precancerous gastric changes (atrophy, intestinal metaplasia) during gastritis, for the purpose of confirming the diagnosis, assessing the risk of gastric cancer development, and determining the schedule for endoscopic surveillance, are recommended to undergo a blood test for pepsinogen I, pepsinogen II, and gastrin-17 [37, 38, 7, 39-42].

GCR ALOE 2Grade of Recommendation A (Level of Evidence – 2)

Comments: The diagnosis of atrophic gastritis has become more accessible thanks to serum markers of corpus and antral gastric mucosal atrophy. A low level of serum pepsinogen I has high sensitivity and specificity (84% and 95%, respectively) in diagnosing severe atrophy of the gastric corpus mucosa. Atrophy of the antral mucosa is characterized by low levels of basal and postprandial gastrin-17 due to a decrease in the number of G-cells.

During long-term follow-up of individuals with normal serum pepsinogen levels, regardless of H. pylori status, the incidence of gastric cancer was negligible. In individuals with low pepsinogen levels, indicating atrophic gastritis of the gastric corpus, the incidence of gastric cancer was significantly higher (3.5–6 per 1,000 per year). In this group, the incidence of gastric cancer was higher when H. pylori antibodies were negative, which was associated with severe atrophy and metaplasia preventing further H. pylori colonization [39]. In a study conducted in the Russian Federation, gastric cancer was associated with a low pepsinogen I level (odds ratio (OR) 2.9; 95% confidence interval (CI) 1.3-6.4), a low pepsinogen I to pepsinogen II ratio (OR 3.3; 95% CI 1.5-7.3), and a low gastrin-17 level (OR 1.8; 95% CI 0.7-4.8) [40]. A meta-analysis of 20 studies involving 4,241 patients showed that for the diagnosis of atrophic gastritis, the combined assessment of serum pepsinogen, gastrin-17, and anti-H. pylori IgG antibodies demonstrated a sensitivity of 74.7% (95% CI 62.0-84.3) and a specificity of 95.6% (95% CI 92.6-97.4). The negative predictive value was 91% [38]. A meta-analysis of 31 studies involving 1,520 patients with gastric adenocarcinoma and 2,265 patients with atrophic gastritis demonstrated that serum pepsinogen serves as a reliable non-invasive screening marker for gastric cancer and its precancerous condition, atrophic gastritis [38].

2.4 Instrumental Diagnostics

• All patients, in order to confirm the diagnosis of gastritis and duodenitis, detect and grade precancerous conditions and gastric mucosal changes—primarily the extent and degree of atrophy, intestinal metaplasia, and the presence of dysplasia—in the absence of contraindications, are recommended to undergo esophagogastroduodenoscopy (EGD) [25, 26, 32, 33, 41, 42, 43, 44, 45, 190].

GCR ALOE 2Grade of Recommendation A (Level of Evidence – 2)

Comments: For the diagnosis of precancerous gastric changes using conventional white-light endoscopy, the correlation between endoscopic and histological data is unsatisfactory [41], whereas high-resolution endoscopy results are more reliable. In multicenter prospective studies, the specificity of high-resolution white-light endoscopy for diagnosing intestinal metaplasia was 98%, with a sensitivity of 53% and 59%; for diagnosing neoplasia, specificity was > 95%, and sensitivity was 74% and 29% [26, 44]. In a meta-analysis involving 10 studies and 699 patients, the sensitivity, specificity, and area under the curve (AUC) of dye chromoendoscopy for diagnosing precancerous changes and early gastric cancer were 0.90 (95% CI 0.87 - 0.92), 0.82 (95% CI 0.79–0.86), and 0.95, respectively, which surpasses the results of white-light endoscopy [43].

• All patients for the diagnosis of precancerous conditions and/or gastric mucosal changes are recommended to undergo high-resolution EGD with a multimodal imaging mode, with or without magnification, including targeted biopsies to assess the stage of atrophy and intestinal metaplasia and to detect neoplasia [26, 42, 44, 45, 29, 30, 38, 46].

Level of Evidence AGrade of Evidence 2Level of Recommendations A (Grade of Evidence – 2)

Comments: The multimodal examination mode involves the use of additional endoscopic techniques to improve visualization (chromoendoscopy with vital dyes, digital and optical contrast technologies—NBI, BLI, i-SCAN, FICE, and others). A systematic review showed that NBI endoscopy (in most studies with magnification) demonstrated a sensitivity and specificity of 86% and 77% for diagnosing intestinal metaplasia, and 90% and 83% for diagnosing dysplasia [44]. Based on reproducible NBI endoscopy features, a simplified classification of mucosal changes was proposed, with a diagnostic accuracy of 84% for intestinal metaplasia and 95% for dysplasia. It was noted that these results depend on professional training and are better among experienced endoscopists [45]. In a prospective multicenter study using this classification, the sensitivity and specificity for diagnosing intestinal metaplasia were 87% and 97%, and for diagnosing dysplasia, 92% and 99% [26].

• All patients undergoing diagnostic EGD for the first time, for adequate staging of precancerous gastric mucosal conditions in patients with suspected atrophic, metaplastic, and neoplastic changes, are recommended to undergo a biopsy (followed by pathological examination of the gastric biopsy material, including the use of histochemical and immunohistochemical methods) both for the diagnosis of H. pylori infection and for identifying the stages of atrophic gastritis [47-52, 53, 54].

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

• Performing a gastric biopsy followed by pathological examination of the gastric biopsy material is recommended from two regions (two biopsy specimens each from the corpus and the antrum along the lesser and greater curvatures). Biopsy specimens from the corpus and antrum must be clearly labeled and placed in separate containers. An additional biopsy should be taken from each visible pathological area of the gastric mucosa. If OLGA or OLGIM staging systems are planned to be used to assess the severity of atrophic gastritis, an additional biopsy from the incisura angularis may be taken [47-52].

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

Comments: The diagnosis of "gastritis" is traditionally viewed as a morphological diagnosis. According to the requirements of the Updated Sydney System, at least five biopsy specimens are required for the correct interpretation of the gastric mucosa. The designated sites for obtaining biopsy material are: 2 from the antrum at a distance of 3 cm from the pylorus along the greater and lesser curvatures, 2 from the gastric corpus midway along the greater curvature and 4 cm proximal to the incisura along the lesser curvature, and 1 from the incisura angularis [15]. Currently, chromoendoscopy provides precision biopsy sampling, which, combined with biopsies from fixed points, ensures better diagnosis of precancerous changes. Biopsy from the incisura angularis allows for a more accurate determination of precancerous changes, especially when chromoendoscopy and other advanced imaging endoscopy methods are unavailable. Biopsy from the incisura angularis allows for a more accurate staging according to OLGA and OLGIM, which correlate with the risk of gastric cancer [41, 50, 51, 52].

2.5 Other Procedures

2.5.1. Primary diagnosis of H. pylori infection

• All patients with suspected gastritis for the primary diagnosis of H. pylori are recommended to be prescribed reference diagnostic methods for H. pylori infection—the 13C-urea breath test (13C-urea breath test for Helicobacter pylori) and laboratory-based monoclonal stool H. pylori antigen testing [55, 56].

Level of Evidence 1Grade of Recommendation A (Level of Evidence — 1).

Comments: The most optimal tests for the primary diagnosis of H. pylori infection are non-invasive methods (not requiring esophagogastroduodenoscopy): the ¹³C-urea breath test and monoclonal H. pylori stool antigen testing. According to a Cochrane review and meta-analysis, the sensitivity of the ¹³C-breath test is 94% (95% CI: 0.89 - 0.97), and stool H. pylori antigen testing is 83% (95% CI: 0.73 - 0.90), with a specificity of 90% [55].

• For patients who have indications for esophagogastroduodenoscopy, a rapid urease test with biopsy of the gastric antrum and body [57-60] or determination of Helicobacter pylori DNA in gastric mucosal biopsies by PCR [61-63] may be recommended as primary diagnostic methods.

GUD 2Level of Recommendation B (Level of Evidence — 2).

Comments: A rapid urease test can be used as a primary diagnostic method for H. pylori during EGD. When using endoscopic diagnostic methods for H. pylori, at least 2 biopsy specimens from the gastric body and 1 biopsy specimen from the antrum should be taken [57-60]. The sensitivity of the RUT ranges from 85% to 95%, and specificity from 95% to 100% [61]. For H. pylori PCR diagnostics, a biopsy specimen previously placed in the rapid urease test medium can be used [62, 63].

Comments: It should be taken into account that treatment with proton pump inhibitors (PPIs) can lead to false-negative results in most diagnostic tests [6, 9, 64, 65]. It is recommended to discontinue PPIs at least 2 weeks before diagnostic procedures [6, 9]. Systemic antibacterial drugs and bismuth preparations should be discontinued at least 4 weeks before diagnostic tests [6].

• For some patients, including those with a reduced degree of bacterial colonization of the gastric mucosa (e.g., after recent intake of antisecretory or antibacterial drugs, in case of ulcer bleeding, or atrophic gastritis), serological testing for IgG antibodies to H. pylori (determination of antibodies to Helicobacter pylori in the blood) may be recommended as the primary diagnosis of the infection [55, 66].

GUD 3Level of Recommendation B (Level of Evidence — 3).

2.2. Diagnosis of H. pylori after eradication therapy

• All patients are recommended to undergo a 13C-urea breath test (13C-urea breath test for Helicobacter pylori) [55, 56] or laboratory-based stool H. pylori antigen testing [55, 67] no earlier than 4 weeks after the completion of anti-H. pylori therapy or after the end of treatment with antisecretory agents (PPIs) or bismuth tripotassium dicitrate** to assess the efficacy of eradication therapy [55, 56].

GUD 1Level of Recommendation A (Level of Evidence — 1).

• Serological methods for determining antibodies to H. pylori are not recommended for diagnosing the efficacy of performed eradication therapy, as they are not applicable in this situation [55, 6].

GUD 3Level of Recommendation B (Level of Evidence — 3).

• In the absence of reference diagnostic methods, it is advisable to combine available diagnostic tests or (in case of methods for direct detection of the bacterium in a gastric mucosal biopsy specimen – bacteriological, morphological, rapid urease test) examine at least two biopsy specimens from the gastric body and one biopsy specimen from the antrum [57-60, 9].

GUD 3Level of Recommendation B (Level of Evidence — 3).

Comments: To monitor eradication, which is performed at least 4 weeks after the completion of eradication therapy, it is best to use a ¹³C-urea breath test or H. pylori stool antigen test [55]. To avoid false-negative results, PPI intake must be stopped 2 weeks before the scheduled follow-up test, and the intake of any antibacterial drugs or bismuth tripotassium dicitrate** 4 weeks before the planned follow-up test [6].

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1 Medical treatment

3.1.1. Eradication therapy for H. pylori infection

• All patients with chronic gastritis who test positive for H. pylori infection are recommended to undergo eradication therapy as etiological treatment [3, 68-73, 7].

Level of Evidence BLevel of Confidence 2Level of recommendation B (level of evidence – 2).

• All patients with atrophic gastritis who test positive for H. pylori infection are recommended to undergo eradication therapy to prevent the progression of atrophy [74-76, 6, 7].

GoR ALoE 2Grade of Recommendation A (Level of Evidence – 2).

Comments: H. pylori serves as the etiological factor of chronic gastritis. Eradication therapy for the infection cures non-atrophic gastritis, which is accompanied by well-studied histological changes: infiltration of the epithelium and lamina propria by polymorphonuclear leukocytes disappears early; infiltration by lymphocytes and plasma cells decreases fairly early, but does not completely disappear for more than a year after eradication; lymphoid follicles also persist for more than a year after etiological treatment, although their number decreases [68-73]. According to several meta-analyses, H. pylori eradication results in regression or, at least, stabilization of mucosal atrophy in the gastric body and antrum, while only stabilization, but not reversal, of intestinal metaplasia can be achieved [74-76].

• All patients with gastritis who test positive for H. pylori infection and have indications for eradication therapy are recommended to be prescribed, as a first-line eradication therapy ensuring a high eradication rate, a choice of:

- standard triple therapy including a PPI (in a standard dose twice daily), clarithromycin** (500 mg twice daily), and #amoxicillin** (1000 mg twice daily orally), augmented with bismuth tripotassium dicitrate** (120 mg 4 times a day or 240 mg twice a day) for 14 days [77, 78]

GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).

or

- classic quadruple therapy with bismuth tripotassium dicitrate** (120 mg 4 times a day) combined with a PPI (in a standard dose twice daily), #tetracycline (500 mg 4 times a day orally), and metronidazole** (500 mg 3 times a day) for 14 days [79-81]

GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).

or

- bismuth-free quadruple therapy, which includes standard triple therapy (PPI in a standard dose twice daily), #amoxicillin** (at a dose of 1000 mg twice daily orally), clarithromycin** (500 mg twice daily), augmented with metronidazole** (500 mg 3 times a day) for 14 days [81, 191].

GCR ALoE 2Grade of Recommendation A (Level of Evidence – 2).

Comments: The empirical choice of a first-line eradication therapy regimen without determining the susceptibility of H. pylori to systemic antibacterial drugs is based on therapy with maximum proven efficacy. The addition of bismuth tripotassium dicitrate** to standard triple therapy reliably increases the cure rate of the infection above 90% according to the "European Registry on H. pylori Management" [78]. According to a meta-analysis by S.W. Ko et al., augmenting standard triple therapy with a bismuth preparation increases efficacy with an odds ratio of 2.81 (95% CI 2.03-3.89), including in cases of proven H. pylori resistance to clarithromycin** [77]. In the 2018 edition of the "Guidelines of the Russian Gastroenterological Association for the Diagnosis and Treatment of H. pylori Infection in Adults," the inclusion of bismuth tripotassium dicitrate** in the H. pylori eradication regimen is termed a measure that increases the efficacy of eradication therapy [82]. Standard triple therapy augmented with a bismuth preparation exceeds 90% efficacy in routine clinical practice according to Russian data [83-86]. The addition of a bismuth preparation to other eradication regimens, including those with levofloxacin**, has also demonstrated high efficacy [79-81]. Classic bismuth tripotassium dicitrate**-based quadruple therapy continues to demonstrate an eradication efficacy of over 90% according to both the European registry [78] and meta-analyses [80,81]. Bismuth-free quadruple therapy or concomitant therapy, including a PPI and a combination of amoxicillin**, clarithromycin**, and metronidazole**, is not inferior in efficacy to classic quadruple therapy according to meta-analysis [81]. In essence, concomitant therapy is a standard triple regimen augmented with metronidazole** [82].

• Patients with positive test results for H. pylori infection and indications for eradication therapy are recommended to receive standard triple therapy as first-line eradication therapy in regions where its efficacy is confirmed, for 14 days [87].

GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).

Comments: According to European registry data, standard triple therapy for 7 days leads to successful eradication in 82.7%; 10 days in 84.2%; 14 days in 86.2% [79]. A Cochrane meta-analysis of 45 randomized controlled trials in parallel groups shows an increase in the H. pylori eradication rate with triple therapy when the treatment duration is extended from 7 to 14 days (72.9% vs. 81.9%), while the relative risk (RR) of H. pylori persistence is 0.66 (95% CI 0.60 – 0.74), and the NNT is 11 (95% CI 9 – 14). A significant effect was observed with the combination of a PPI with clarithromycin** and amoxicillin** (34 studies, RR 0.65, 95% CI 0.57 – 0.75; NNT 12, 95% CI 9 – 16). A significant increase in H. pylori eradication success accompanies the extension of triple therapy from 7 to 10 days (24 studies, 75.7% vs. 79.9%; RR 0.80, 95% CI 0.72 – 0.89; NNT 21, 95% CI 15 – 38) and from 10 to 14 days (12 studies, 78.5% vs. 84.4%; RR 0.72, 95% CI 0.58 – 0.90; NNT 17, 95% CI 11 – 46); especially for the combination of a PPI with clarithromycin** and amoxicillin** when increasing the duration from 7 to 10 days (17 studies, RR 0.80, 95% CI 0.70 – 0.91) and from 10 to 14 days (10 studies, RR 0.69, 95% CI 0.52 – 0.91) [87]. In the 2018 edition of the Russian Gastroenterological Association Guidelines for the Diagnosis and Treatment of H. pylori Infection in Adults, increasing the duration of H. pylori eradication therapy to 14 days is cited as a measure that increases the efficacy of eradication therapy [82]. The Maastricht VI EHMSG Consensus establishes a treatment duration of 14 days for all eradication regimens [6].

• In patients with gastritis who test positive for H. pylori infection and have indications for eradication therapy, prescribing a double dose of a proton pump inhibitor may be used as a measure to increase the efficacy of anti-Helicobacter treatment [88].

GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).

Comments: A meta-analysis demonstrated an increase in the H. pylori eradication rate when administering a high dose of a PPI [88]. In the 2018 edition of the Russian Gastroenterological Association Guidelines for the Diagnosis and Treatment of H. pylori Infection in Adults, preference was given to newer PPIs: rabeprazole and esomeprazole** [82]. Rabeprazole has specific characteristics (an intrinsic anti-Helicobacter effect, stimulation of mucin secretion in the gastric mucosa) that may provide additional advantages in H. pylori eradication [82]. In the Maastricht IV Consensus, a preference for these PPIs is not emphasized [6]. For example, an attempt to demonstrate an increase in treatment efficacy depending on the dose of rabeprazole and esomeprazole** via meta-analysis was not confirmed (85.3% successful therapy with "high" doses and 84.2% with "standard" PPI doses, OR 1.09 (95% CI 0.86–1.37), P = 0.47) [89]. This result may be a consequence of including studies with a low daily dose of rabeprazole (10 mg twice daily) used in some Asian countries [89]. The high efficacy of rabeprazole and esomeprazole** for H. pylori eradication shows little dependence on phenotypically determined variants of hepatic metabolism. A meta-analysis of 16 randomized controlled trials (n=3680) demonstrated a decrease in the efficacy of standard-dose triple therapy with omeprazole** and lansoprazole in rapid PPI metabolizers, whereas the efficacy of standard-dose triple therapy with rabeprazole and esomeprazole** did not depend on CYP2C19 genetic polymorphism and did not decrease in rapid PPI metabolizers [90].

• In patients with gastritis who test positive for H. pylori infection and have indications for eradication therapy, prescribing a potassium-competitive acid blocker (vonoprazan) may be used as a measure to increase the efficacy of anti-Helicobacter treatment [91, 92].

Level of Evidence BLevel of Confidence 2Level of recommendation B (level of evidence – 2).

Comments: A meta-analysis by Y.S. Jung et al. demonstrated an increase in the H. pylori eradication rate when triple therapy with vonoprazan was prescribed compared to triple therapy with "classic" PPIs [91]. A meta-analysis by S. Shinozaki et al. also showed the superiority of vonoprazan-based eradication therapy when comparing the efficacy of various second-line eradication regimens [92].

• In patients with gastritis who test positive for H. pylori infection and have indications for eradication therapy, the addition of rebamipide to eradication regimens may be used as a measure to increase the efficacy and improve the tolerability of anti-Helicobacter treatment [93–95].

GCR ALEL 1Grade of Recommendation A (Level of Evidence – 1)

Comments: Three meta-analyses involving 6, 11, and 6 randomized controlled trials confirmed an increased eradication rate when rebamipide at a dose of 100 mg 3 times daily was included in the regimens, as well as improved tolerability of the administered treatment [93–95].

• In patients with gastritis who test positive for H. pylori infection and have indications for eradication therapy, it is recommended to ensure adherence to the prescribed treatment (compliance) upon its initiation [96, 97].

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

Comments: Compliance should be considered a key factor in the success of H. pylori eradication therapy. A controlled study showed that when taking more than 60% of the prescribed medications, infection eradication was 96%, while taking less than 60% (low compliance) resulted in 69% [96]. In a large-scale randomized controlled trial, the eradication rate decreased by 34% in patients with low compliance (taking less than 80% of the prescribed medications), with H. pylori persistence observed in 59% of non-compliant cases [97]. The World Gastroenterology Organisation global guidelines on H. pylori outline best practices for improving patient adherence to eradication therapy. Patients must be informed that successful eradication depends on adhering to the treatment regimen. Time should be taken to counsel the patient, explain how to take the complex drug therapy, and discuss potential side effects of antibiotic therapy. The necessity of completing the course of treatment and taking the prescribed total dose of medications should be specifically emphasized. It is highlighted that written or graphic information on how to take complex eradication therapy can promote compliance [https://www.worldgastroenterology.org/UserFiles/file/guidelines/helicobacter-pylori-russian-2021.pdf]. For the treatment of peptic ulcer disease, a combination drug is registered in the Russian Federation that contains a set of capsules and tablets for standard triple therapy: each blister strip containing 2 capsules of omeprazole 20 mg, 2 tablets of clarithromycin 500 mg, and 4 capsules of amoxicillin 500 mg is designed for 1 single day with clear instructions for morning and evening intake. A ready-to-use kit of medications for eradication therapy ensures correct dosing and consistent administration frequency, and improves patient compliance, which is the basis for the >90% infection eradication rate in peptic ulcer disease obtained in a domestic study [98].

• In patients with gastritis who test positive for H. pylori infection and have indications for eradication therapy, the prescription of strain-specific probiotics (ATC code A07F: Antidiarrheal microorganisms) that have proven efficacy may be used to reduce the incidence of adverse events, including antibiotic-associated diarrhea [99–110].

GCR ALEL 1Grade of Recommendations A (Level of Evidence – 1)

Comments: Certain single-strain and multi-strain probiotics have proven efficacy during H. pylori eradication therapy [99–106]. It is hypothesized that the administration of probiotics reduces the incidence of adverse events, leading to a potential increase in compliance and, consequently, an increase in eradication efficacy [6].

A meta-analysis of 42 RCTs showed that the risk of developing antibiotic-associated diarrhea in patients taking probiotics was significantly lower compared to patients who did not take them (RR = 0.35; 95% CI: 0.27–0.47, p < 0.00001) or who received a placebo during antibacterial treatment (RR = 0.69; 95% CI: 0.60–0.80, p < 0.00001) [107]. A meta-analysis of 7 RCTs focusing on the use of probiotics together with systemic antibacterial drugs exclusively during H. pylori eradication noted a significant 45% reduction in the risk of developing antibiotic-associated diarrhea (RR = 0.55; 95% CI: 0.41–0.73, p < 0.0001) [107].

According to a meta-analysis of 31 RCTs, the administration of probiotics during antibacterial therapy also reduces the risk of C. difficile-associated diarrhea by 60% (OR=0.40; 95% CI: 0.30-0.52) compared to placebo or no probiotic support [108].

A randomized study demonstrated that the inclusion of the probiotic Saccharomyces boulardii (S. boulardii) CNCM I-745 at a dose of 750 mg per day for the entire treatment period in a triple eradication regimen significantly reduced the number of adverse effects during therapy compared to the control group (5.3±3.0 vs. 9.0±3.1, P = 0.028) [109]. The H. pylori eradication rate in patients taking S. boulardii CNCM I-745 at a dose of 500 mg daily was significantly higher than that in the control group (86.0% and 74.7%, respectively; p = 0.02). Compared with the control group, patients in the experimental group experienced significantly fewer adverse effects of eradication (17.0% vs. 55.7%; p < 0.001), including the development of antibiotic-associated diarrhea (2.0% vs. 46.4%; P = 0.02), and also showed higher treatment adherence (95.0% of participants in the experimental group completed the full course of therapy compared to 91.2% in the control group, p < 0.001) [110]. A meta-analysis of 18 studies (n=3592) showed that adding S. boulardii to eradication therapy reduced the risk of overall adverse events (dyspepsia, stool abnormalities) by 53% compared to regimens without S. boulardii (OR= 0.47, 95% CI: 0.36-0.61), the incidence of diarrhea by 67% (OR= 0.37, 95% CI: 0.23-0.57), and increased successful eradication rates (OR= 1.09, 95% CI: 1.05-1.13) [100].

Based on a meta-analysis, probiotics containing Lactobacillus acidophilus LA-5 and Bifidobacterium animalis subsp. lactis BB-12 (predominantly as functional food products) are effective in reducing the total number of adverse events (OR 0.31, 95% CI 0.20-0.47), preventing antibiotic-associated diarrhea (OR 0.38, 95% CI 0.20-0.72), and improving H. pylori eradication outcomes (OR 1.16, 95% CI 1.05-1.28) [101].

• Patients with gastritis who test positive for H. pylori infection and have indications for eradication therapy may be prescribed metabiotics (as part of a dietary supplement) to increase its efficacy and reduce the incidence of adverse events [111].

GPP BLOE 3Grade of Recommendation B (Level of Evidence – 3).

Comments: Metabiotics (postbiotics) include non-viable bacteria or their components, as well as microbial metabolic products that exhibit biological activity in the human body [112, 113]. The efficacy of metabiotics in H. pylori eradication was demonstrated in a multicenter randomized clinical trial involving 90 adult patients with gastritis and/or peptic ulcer disease. A significant improvement in standard triple eradication therapy outcomes was shown when incorporating a metabiotic containing inactivated Lactobacillus reuteri DSM 17648 at a dose of 1×10¹⁰ CFU twice daily (p=0.024). According to 13C-urea breath test results, successful eradication was achieved in 86.7% of patients receiving the metabiotic and 66.67% of patients in the control group treated with the triple therapy components alone. Patients receiving the metabiotic experienced treatment-related side effects such as nausea (60% vs. 86.67%, p=0.033), diarrhea (36.6% vs. 50%, p=0.035), constipation (20% vs. 33.3%, p=0.026), and dysgeusia (43.3% vs. 60%, p=0.047) less frequently, although bloating was observed more often (40% vs. 13.3%, p < 0.001) [111].

• For patients with positive H. pylori test results after failure of standard triple therapy, standard triple therapy, potentiated with bismuth tripotassium dicitrate**, or concomitant therapy, it is recommended as second-line therapy classical quadruple therapy with bismuth tripotassium dicitrate**—bismuth tripotassium dicitrate** (120 mg 4 times daily) combined with a PPI (at a standard dose twice daily), #tetracycline (500 mg 4 times daily orally), and #metronidazole** (500 mg 3 times daily) for 14 days [114, 115, 192].

LoR CGoE 1Level of Recommendation C (Level of Evidence – 1)

Comments: A systematic review with a network meta-analysis demonstrated high efficacy of bismuth-containing quadruple therapy as second-line therapy [114]. According to a meta-analysis by Z. Han et al., bismuth-containing regimens increase the eradication rate in clarithromycin** resistance by 40%, in metronidazole** resistance by 26%, and in dual resistance by 59%, making them a justified choice as second-line therapy [115].

• For patients with positive H. pylori test results after failure of classical quadruple therapy with bismuth tripotassium dicitrate**, a triple treatment regimen with #levofloxacin** (PPI at a standard dose twice daily, #levofloxacin** 500 mg twice daily orally, and #amoxicillin** 1000 mg twice daily orally) or a quadruple regimen with #levofloxacin** (PPI at a standard dose twice daily, #levofloxacin** 500 mg twice daily orally, #amoxicillin** 1000 mg twice daily orally, and bismuth tripotassium dicitrate** 120 mg 4 times daily) for 14 days is recommended as second-line therapy [114, 116-118].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: Triple therapy with #levofloxacin (PPI, #levofloxacin**, and #amoxicillin**) or quadruple therapy with #levofloxacin** (PPI, #levofloxacin**, #amoxicillin**, bismuth preparation) following the failure of previous eradication therapy courses has been evaluated in controlled studies and systematic reviews [114, 116-118].

The algorithm for the diagnosis and treatment of H. pylori infection is presented in Figure 1 (Appendix B).

3.1.2. Medical therapy for erosive gastritis and duodenitis

• For patients with erosive gastritis and duodenitis, including those associated with the use of nonsteroidal anti-inflammatory and antirheumatic drugs, antisecretory therapy with proton pump inhibitors for 4-6 weeks [119-123] and/or rebamipide for 4-8 weeks [124, 125] is recommended to achieve erosion healing.

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

Comments: Basic antisecretory therapy using PPIs (prescribing #omeprazole** orally at a daily dose of 20 mg [122], #lansoprazole orally 30 mg, #pantoprazole orally 40 mg, #rabeprazole orally 20 mg, #esomeprazole** orally 20 mg for 2-4 weeks, or longer if necessary) serves as the primary treatment method for gastroduodenal erosions, including those induced by nonsteroidal anti-inflammatory and antirheumatic drugs [119-123, 193, 194]. The efficacy of rebamipide in healing erosive gastritis has been proven in clinical studies, including randomized trials [124, 125].

3.1.3. Cytoprotective medical therapy

• For patients with chronic gastritis, including atrophic gastritis, therapy with bismuth tripotassium dicitrate** [126, 127, 82] or rebamipide for 4-8 weeks [128-132, 82, 133, 134] may be recommended to potentiate the protective properties of the mucous membrane.

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

Comments: The cytoprotective effect of bismuth tripotassium dicitrate** is due to the binding of free radicals by bismuth ions and the enhancement of endogenous prostaglandin synthesis [126]. A cohort study demonstrated a reduction in DNA damage in the generative zone of the gastric mucosa in patients after successful H. pylori eradication during a 4-week course of therapy with bismuth tripotassium dicitrate** [127]. Rebamipide exerts a protective effect on the gastrointestinal mucosa by regulating prostaglandin levels, restoring physiological mucus production and tight junctions, and inhibiting oxidative stress products, proinflammatory cytokines, and chemokines, which collectively lead to the resolution of mucosal increased permeability syndrome [10, 133, 134]. In randomized controlled trials, rebamipide reduced inflammation and, in one study, even decreased intestinal metaplasia and low-grade dysplasia, contributing to the prevention of gastric cancer in high-risk patients [128-132].

3.1.4. Medical therapy for dyspepsia symptoms

• For all patients presenting to a physician for the first time with complaints of pain and burning in the epigastric region, feeling of epigastric fullness, early satiety—that is, patients with uninvestigated dyspepsia who test positive for H. pylori infection—H. pylori eradication therapy is recommended to relieve dyspeptic symptoms and establish a diagnosis of functional dyspepsia [135].

GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).

Comments: According to a systematic review evaluating the efficacy of H. pylori eradication therapy in the treatment of functional dyspepsia, an analysis of 29 clinical trials involving 6,781 patients demonstrated that eradication therapy is significantly more effective for resolving (number needed to treat (NNT) 14 [95% CI 11–21]) or reducing (NNT 9 [95% CI 7–17]) dyspeptic symptoms. Thus, it was shown that the positive effect of anti-Helicobacter therapy in patients with functional dyspepsia is statistically significant, albeit modest [135]. The Kyoto Consensus report on Helicobacter gastritis legitimized the term "H. pylori-associated dyspepsia", viewing this variant of dyspepsia as a separate entity ("distinct entity") [7]. In H. pylori-infected patients with dyspepsia, symptoms may be caused by Helicobacter gastritis if successful eradication is followed by sustained remission. If dyspepsia persists after the etiological treatment of bacterial gastritis, a diagnosis of functional dyspepsia should be established [7].

• In patients with chronic gastritis and dyspeptic symptoms (especially such as epigastric pain and burning), including those combined with functional dyspepsia, proton pump inhibitor therapy is recommended as symptomatic treatment [136, 137, 138, 139, 140].

GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).

Comments: Acid hypersensitivity, decreased duodenal clearance, and altered gastric motility induced by acidic duodenal reflux provide the rationale for prescribing acid-suppressive therapy in functional dyspepsia, particularly in epigastric pain syndrome [139, 140]. A meta-analysis of 8 RCTs involving 2,216 patients with FD showed that PPIs were more effective than placebo in improving symptoms, with symptom improvement observed in 36.0% of the PPI group and 30.0% of the placebo group (relative risk (RR) 1.41; 95% CI 1.07–1.87). The number needed to treat (NNT) was 9 (95% CI, 6–24). PPIs proved effective in terms of symptom relief (RR 1.44; 95% CI 1.03–2.01) and complete symptom resolution (RR 1.26; 95% CI 1.07–1.49) [139].

• In patients with chronic gastritis and dyspeptic symptoms (especially such as postprandial fullness and early satiety), including those combined with functional dyspepsia, therapy with prokinetic agents is recommended as symptomatic treatment [138, 141-145].

GGR BLOC 1Grade of Recommendation B (Level of Evidence – 1).

Comments: Acotiamide is a reversible acetylcholinesterase inhibitor and presynaptic muscarinic receptor antagonist. Its prokinetic effect is achieved by enhancing acetylcholine release from presynaptic terminals and reducing its degradation by acetylcholinesterase [146]. The efficacy of acotiamide compared to placebo in reducing dyspeptic symptoms has been demonstrated in clinical trials [146, 147] and meta-analyses [141, 142], including a dedicated meta-analysis comparing acotiamide and placebo (6 RCTs involving 2,429 patients with FD) [142]. The drug does not cause QT interval prolongation or extrapyramidal disorders, and its safety profile is comparable to placebo, as confirmed by a study involving acotiamide intake for more than 50 weeks [146] and meta-analyses [141, 142]. Acotiamide does not affect the results of the 13C-urea breath test in H. pylori-positive patients with functional dyspepsia [148].

Itopride, by its mechanism of action, is both a dopamine receptor antagonist and an acetylcholinesterase blocker. The drug activates acetylcholine release and prevents its degradation [149]. The results of a large RCT indicated that after 8 weeks of treatment, clinical symptoms of dyspepsia completely disappeared or significantly decreased in severity in 57%, 59%, and 64% of patients receiving itopride (at doses of 50, 100, and 200 mg 3 times daily, respectively), which significantly exceeded the placebo effect (41%) [149]. The efficacy of itopride has been confirmed in other studies, including those conducted in Russia [150, 151]. A meta-analysis of 9 RCTs involving 2,620 patients with FD demonstrated a significantly higher efficacy of itopride in improving general well-being, reducing postprandial epigastric heaviness, and alleviating early satiety. The incidence of adverse effects was identical in the itopride and placebo groups [144].

Trimebutine, an agent acting on the enkephalinergic system of the gastrointestinal tract and thus normalizing its motility, has demonstrated high efficacy in RCTs for relieving dyspeptic symptoms such as postprandial fullness, early satiety, and abdominal pain in patients with FD, as well as in patients with FD combined with irritable bowel syndrome [152, 153]. The ability of trimebutine to relieve dyspeptic symptoms has been confirmed in large-scale prospective non-interventional studies conducted in the Russian Federation, with a total of 4,533 participants [154, 155]. According to a network meta-analysis evaluating prokinetic agents in functional dyspepsia, trimebutine demonstrated efficacy comparable to metoclopramide** and domperidone in terms of the surface under the cumulative ranking curve (SUCRA) [143]. Furthermore, the safety profile of trimebutine, according to meta-analyses, did not differ from placebo [143, 156].

Domperidone, which is a dopamine receptor antagonist by mechanism of action, demonstrated efficacy in reducing dyspeptic symptoms in a meta-analysis (RR 7.0 [95% CI 3.6–16]) [145]. However, adverse events such as QTc interval prolongation and the associated risk of cardiac arrhythmias (especially when co-administered with drugs metabolized by the CYP3A4 system, like domperidone) have led to restricted indications for domperidone in dyspepsia and limited treatment duration [157, 158]. In this regard, the combination drug Domperidone+Omeprazole (a fixed combination of 20 mg omeprazole and 30 mg modified-release domperidone) is of interest. Clinical efficacy is ensured by the potentiation of actions from different pharmacological groups and high compliance (once-daily administration) [159]. Modified-release domperidone as part of the Domperidone+Omeprazole combination allows the drug to be taken once daily instead of three times daily. At the same time, there are no peak plasma concentrations of domperidone that may occur with conventional dosage forms, thereby reducing the likelihood of dose-dependent adverse reactions. The plasma concentration of domperidone during the use of the fixed combination of 20 mg omeprazole and 30 mg modified-release domperidone does not exceed the limits of a single 10 mg dose, allowing the drug to be prescribed for course treatment of dyspeptic symptoms [157–159].

• In patients with chronic gastritis and dyspeptic symptoms, treatment with #rebamipide (100 mg 3 times daily for 2–4 weeks, if necessary up to 8 weeks) either as monotherapy or as part of combination therapy is recommended to relieve these symptoms [160].

GOM ALOE 1Grade of Recommendation A (Level of Evidence – 1).

Comments: According to a meta-analysis of 17 RCTs, rebamipide significantly reduces dyspeptic symptoms not only in functional dyspepsia but also in NSAID-induced gastritis [160].

3.2. Endoscopic treatment

• In patients with chronic gastritis upon the detection of endoscopically visible neoplasms with low-grade or high-grade dysplasia, as well as cancerous lesions, staging of the process and appropriate treatment are indicated, including endoscopic en bloc resection of the neoplasm [161, 162, 46, 42].

Level of Evidence AGrade of Evidence 2Level of Recommendations A (Grade of Evidence – 2)

Comments: Epithelial dysplasia represents histologically unequivocal neoplastic epithelium (cellular atypia, disturbed histoarchitecture) without reliable signs of invasion and serves as the penultimate stage of gastric carcinogenesis [163, 164]. In patients with high-grade dysplasia followed for 4–48 months, the proportion of patients developing cancer or metachronous cancer ranged from 60–85%; in patients with low-grade dysplasia followed for 10–48 months, cancer development was observed in 0–23% of cases [162]. A meta-analysis shows that when biopsies are performed for low-grade dysplasia, subsequent pathological examination establishes a diagnosis of high-grade dysplasia in 25% of cases and cancer in 7% [161]. Thus, when a pathological area of epithelial dysplasia is detected, biopsy sampling has low efficacy for an accurate diagnosis, and endoscopic treatment serves as the management of choice.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

• In patients with chronic gastritis in remission, sanatorium-and-spa treatment is recommended [165].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: Sanatorium-resort treatment is not prescribed for patients with contraindications to resort treatment or any balneological procedures (for example, patients with Ménétrière's disease, gastric polyposis, and gastric neoplasms). It is essential to consider the patient's age and concomitant diseases, which determine the choice of the climatic region. The leading non-pharmacological methods of sanatorium-resort rehabilitation include natural environmental factors (climate, mineral water, therapeutic mud), artificially modeled natural factors, kinesiotherapy (various forms and means of medical gymnastics, medical massage), psychotherapy, diet therapy, phytotherapy, and others. Rehabilitation of patients at the sanatorium stage is carried out in accordance with specific regimens—gentle, tonic, and training—which are chosen depending on the length of stay in the sanatorium, the nature of the disease, and the body's adaptive capabilities. Patients with chronic gastritis and reduced gastric secretory function are prescribed drinking medium- and high-mineralized sodium chloride and sodium bicarbonate waters (resorts of Bobruisk, Goryachy Klyuch, Yessentuki, Nalchik, Staraya Russa, Ust-Kachka, etc.). To stimulate the secretion of gastric juice and hydrochloric acid, mineral water is prescribed 15–20 minutes before meals, 3 times a day. Patients with chronic gastritis and increased gastric secretory function are prescribed drinking low- and medium-mineralized carbonated sodium bicarbonate, sodium-calcium, and calcium-magnesium-sodium sulfate waters (Borjomi, Berezovsky mineral waters, Darasun, Zheleznovodsk, Izhevsk mineral waters, etc.). Mineral water is prescribed 1–1.5 hours before meals, 3 times a day [165].

5. Prevention and Dispensary Observation

• All individuals with H. pylori infection in the absence of contraindications are recommended to undergo eradication therapy for the prevention of gastric cancer [166, 167, 168, 169, 170, 6, 7, 8, 46, 42, 82].

GCR BLoE 1Grade of Recommendation B (Level of Evidence – 1)

Comments: H. pylori eradication is recognized as the main method for preventing gastric cancer, the efficacy of which has been proven in a number of population-based studies and meta-analyses [166–170]. In a meta-analysis of 7 RCTs involving 8,323 individuals, H. pylori eradication reduced the incidence of gastric cancer compared to individuals who did not receive eradication therapy, with a relative risk of 0.54 (95% CI 0.40–0.72; NNT = 72), as well as gastric cancer mortality with a relative risk of 0.61 (95% CI 0.40–0.92; NNT = 135) [167].

• All patients who have undergone endoscopic resection of an adenoma/early gastric cancer are recommended to receive H. pylori eradication therapy for the prevention of metachronous gastric cancer [167, 171–173, 6, 7, 8, 46, 42, 82, 174].

GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)

Comments: A reduction in the frequency of metachronous gastric cancer in patients after H. pylori eradication compared to the persistent infection group has been proven in RCTs and meta-analyses [167, 171–173]. Thus, in a meta-analysis of 3 studies involving 1,841 patients who underwent endoscopic resection of epithelial dysplasia/neoplasia, eradication therapy reduced the incidence of gastric cancer with a relative risk of 0.49 (95% CI 0.34–0.70, NNT = 21) [167].

• Patients with detected gastric mucosal dysplasia in the absence of a distinct neoplasm visible during standard white-light endoscopy are recommended to immediately undergo repeat high-resolution esophagogastroduodenoscopy with chromoendoscopy (virtual or dye-based) and magnification. If a distinct neoplasm is again not detected during the repeated examination, it is recommended to perform a gastric biopsy to determine the stage of gastritis (if not done previously) and a follow-up esophagogastroduodenoscopy no later than 6 months (for high-grade dysplasia) and no later than 12 months (for low-grade dysplasia) [175–182, 46, 42].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• For patients with mild to moderate mucosal atrophy limited solely to the antrum, endoscopic surveillance after successful H. pylori eradication therapy is not recommended [175–182, 46, 42].

GCR BLoE 3Level of Evidence B (Level of Confidence of Evidence – 3)

• For patients with intestinal metaplasia limited to a single anatomical region, surveillance is in most cases not recommended, especially if high-quality endoscopy with biopsy has ruled out advanced stages of atrophic gastritis. However, if such patients have a family history burdened by gastric cancer, incomplete intestinal metaplasia, or persistent H. pylori infection, they are recommended to undergo endoscopic surveillance with chromoendoscopy and targeted biopsy once every 3 years [175–184, 46, 42].

GCR BLoE 3Level of Evidence B (Level of Confidence of Evidence – 3)

• Patients with severe atrophic gastritis (severe atrophy and/or intestinal metaplasia in both the body and the antrum — OLGA/OLGIM III/IV) are recommended to undergo high-quality endoscopic surveillance — esophagogastroduodenoscopy every 3 years. Patients with severe atrophic gastritis and a family history burdened by gastric cancer are recommended to undergo esophagogastroduodenoscopy once every 1–2 years [175–184, 46, 42]. In accordance with Order No. 173n of the Ministry of Health of the Russian Federation dated March 29, 2019, "On Approval of the Procedure for Dispensary Observation of Adults," dispensary observation for chronic atrophic fundal and multifocal gastritis includes an appointment (examination, consultation) with a gastroenterologist once a year, and an appointment (examination, consultation) with an oncologist based on medical indications, with monitored stabilization of morphological changes according to EGD with biopsy data.

GCR BLoE 3Level of Evidence B (Level of Confidence of Evidence – 3)

Comments: To determine the intervals for endoscopic surveillance, patient stratification based on the severity of precancerous gastric lesions and additional risk factors for gastric cancer has been proposed. Obviously, individuals with severe atrophy and intestinal metaplasia of the gastric mucosa continue to require endoscopic surveillance even despite the elimination of H. pylori infection as a result of its successful treatment [6, 7, 8, 46, 42, 174]. A population-based study (405,172 individuals, 1979–2011) showed that in individuals who underwent endoscopy with biopsy for non-oncological indications, gastric cancer developed over 20 years in 1 out of 256 individuals with a normal gastric mucosa, 1 out of 85 with gastritis, 1 out of 50 with atrophic gastritis, 1 out of 39 with intestinal metaplasia, and 1 out of 19 with dysplasia [175]. In a cohort study monitoring 1,755 patients with dyspepsia for a mean of 55 months, neoplasia was detected exclusively in individuals with baseline OLGA stages III–IV. The risk of neoplasia was absent in patients with OLGA stages 0, I, and II (95% CI 0–0.4), was 36.5 per 1,000 person-years at stage III (95% CI 13.7–97.4), and 63.1 per 1,000 person-years at stage IV (95% CI 20.3–195.6) [176]. OLGA stages III/IV and OLGIM stages I–IV proved to be independent risk factors for gastric cancer, and even mildly expressed intestinal metaplasia significantly increased the risk of gastric cancer [177, 178]. These studies show that the presence of intestinal metaplasia (as a marker of severe gastritis) may be even more important than the degree of atrophy without intestinal metaplasia, since the risk of gastric cancer was higher with OLGIM I/II than with OLGA III/IV. Incomplete intestinal metaplasia is a prognostically unfavorable factor for the development of gastric cancer compared to complete intestinal metaplasia, and it should be considered as an additional condition for determining the surveillance schedule for patients with gastritis [180–182]. An additional risk factor for gastric cancer is the presence of close relatives suffering from gastric cancer [183, 184].

• Patients with autoimmune gastritis are recommended to undergo endoscopic surveillance once every 1–2 years [46, 42].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: Autoimmune gastritis is a precancerous condition, which justifies endoscopic surveillance. Thus, the relative risk of gastric cancer in pernicious anemia was 6.8 (95% CI 2.6–18.1). A limitation of this meta-analysis is the inclusion of any patients with low vitamin B12 levels, the cause of which is not limited to autoimmune gastritis [185]. Three years after the initial screening examination, 56 patients underwent follow-up EGDs, during which 2 patients with gastric adenocarcinoma, no patients with high-grade dysplasia, and 49 patients with intestinal metaplasia were detected [186]. In another study, no cases of gastric cancer were detected over 6–7 years [187]. The recommended surveillance interval has not been established in randomized controlled trials. Considering the risk of gastric neuroendocrine tumors in addition to the risk of gastric adenocarcinoma, and the combination with other diseases associated with an increased risk of gastrointestinal neoplasms, we recommend endoscopic follow-up once every 3 years.

The algorithm for managing patients with chronic gastritis, along with the follow-up schedule, is shown in Figure 2 (Appendix B).

6. Organization of Medical Care

Most patients with gastritis are eligible for outpatient monitoring and treatment.

Indications for elective hospitalization in patients with gastritis and duodenitis include the need for differential diagnosis of rare forms of gastritis (eosinophilic, granulomatous, etc.), severe anemia in autoimmune gastritis, prominent clinical manifestations in erosive gastritis, the need for H. pylori eradication therapy under direct medical supervision, and the need for endoscopic resection of adenomas and early gastric cancer.

The duration of inpatient treatment for patients with an exacerbation of gastritis should be 16 days.

An indication for emergency hospitalization is the presence of signs of acute gastrointestinal bleeding in a patient with suspected erosive gastritis and/or duodenitis.

Establishment of the clinical diagnosis and patient prognosis, improvement of the clinical presentation, completion of the H. pylori eradication course, performance of endoscopic resection of an adenoma and early gastric cancer, cessation of gastrointestinal bleeding, and improvement of complete blood count parameters serve as the basis for discharge from the hospital.

7. Additional Information

No.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

Rustam A. Abdulkhakov – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Saiyar R. Abdulkhakov – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Olga P. Alekseeva – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Sergey A. Alekseenko – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Dmitry N. Andreev – MD, PhD, Associate Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Andrey Yu. Baranovsky – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Dmitry S. Bordin – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Natalya N. Dekhnich – MD, PhD, Member of the Interregional Association of Clinical Microbiology and Antimicrobial Chemotherapy. No conflict of interest.

Oksana Yu. Zolnikova – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Vladimir T. Ivashkin – MD, PhD, Professor, Academician of the Russian Academy of Sciences, two-time recipient of the Russian Federation Government Prize in Science and Technology (2007) and Education (2013), Honored Doctor of the Russian Federation, Honored Scientist of the Russian Federation, President of the Russian Gastroenterological Association. No conflict of interest.

Irina L. Klyaritskaya – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Roman S. Kozlov – MD, PhD, Professor, Corresponding Member of the Russian Academy of Sciences, President of the Interregional Association of Clinical Microbiology and Antimicrobial Chemotherapy. No conflict of interest.

Evgenia A. Kogan – MD, PhD, Professor, recipient of the Russian Federation Government Prize in Science and Technology (2007), Member of the Russian Society of Pathologists. No conflict of interest.

Aleksey V. Kononov – MD, PhD, Professor, Member of the Russian Society of Pathologists. No conflict of interest.

Mikhail P. Korolev – MD, PhD, Professor, Chairman of the Russian Endoscopic Society, Member of the Russian Society of Surgeons. No conflict of interest

Natalya V. Korochanskaya – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Roman O. Kuvaev – MD, PhD, Member of the Russian Endoscopic Society. No conflict of interest

Tatyana L. Lapina – MD, PhD, Associate Professor, recipient of the Russian Federation Government Prize in Science and Technology (2007), Member of the Russian Gastroenterological Association. No conflict of interest.

Maria A. Livzan – MD, PhD, Professor, Corresponding Member of the Russian Academy of Sciences, Member of the Russian Gastroenterological Association. No conflict of interest.

Maev Igor Veniaminovich, Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Sciences, laureate of the Russian Government Prize in Science and Technology (2006), Honored Doctor of the Russian Federation, Honored Scientist of the Russian Federation, Member of the Russian Gastroenterological Association. No conflict of interest.

Suleyman N. Mammaev – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Marina F. Osipenko – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Pavel V. Pavlov – MD, PhD, Member of the Russian Endoscopic Society. No conflict of interest.

Sergey S. Pirogov – MD, PhD, Member of the Russian Endoscopic Society. No conflict of interest.

Elena A. Poluektova – MD, PhD, Member of the Scientific Community for the Promotion of Clinical Study of the Human Microbiome, Member of the Russian Gastroenterological Association. No conflict of interest.

Aiman S. Sarsenbayeva – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Vladimir I. Simanenkov – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Alexander S. Tertychny – MD, PhD, Professor, Member of the Russian Society of Pathologists. No conflict of interest.

Alexander V. Tkachev – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Alexander S. Trukhmanov – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Anatoly I. Ulyanin – Member of the Scientific Community for the Promotion of Clinical Study of the Human Microbiome, Member of the Russian Gastroenterological Association. No conflict of interest.

Yury P. Uspensky – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Evgeny D. Fedorov – MD, PhD, Professor, Deputy Chairman of the Russian Endoscopic Society. No conflict of interest.

Igor B. Khlynov – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Vladislav V. Tsukanov – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Arkady A. Sheptulin – MD, PhD, Professor, Member of the Russian Gastroenterological Association. No conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

These guidelines aim to provide practitioners with contemporary concepts of the etiology and pathogenesis of gastritis and duodenitis, and to introduce current diagnostic and treatment algorithms.

Target audience for these clinical guidelines:

1. Gastroenterologists

2. General practitioners (family physicians)

3. General practitioners

4. Endoscopists

5. Oncologists

Table 1.Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions)

Table 2. Levels of evidence trustworthiness with the indication of the applied classification of levels of evidence trustworthiness (LET)

Table 3. Levels of recommendation evidence (LRE) indicating the classification system used

Procedure for updating clinical guidelines

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

These clinical guidelines have been developed taking into account the following regulatory and legal documents:

1. Order of the Ministry of Health and Social Development of the Russian Federation dated June 2, 2010 No. 415n "On approval of the Procedure for providing medical care to the population for gastroenterological diseases"

2. Order of the Ministry of Health of the Russian Federation dated May 10, 2017 No. 203n "On approval of criteria for assessing the quality of medical care."

3. Order of the Ministry of Health of the Russian Federation No. 49n dated February 14, 2023, "On Approval of the Standard of Medical Care for Adults with Gastritis and Duodenitis (Diagnosis and Treatment)"

4. Order of the Ministry of Health of the Russian Federation No. 168n dated March 15, 2022, "On Approval of the Procedure for Dispensary Observation of Adults"

Kimura-Takemoto classification of atrophic gastritis [23, 24]. Figure reproduced from [188] in accordance with the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0).

Closed-type gastritis (C-1, C-2, C-3): the boundary of atrophy extends along the lesser curvature of the gastric body without reaching the cardia.

Open-type gastritis (O-1, O-2, O-3, Op): the boundary of atrophy reaches the cardia and extends along the anterior and posterior walls of the gastric body.

C-1 – atrophy is restricted to the antrum

C-2 – atrophy extends above the angular notch but is limited to a small area of the lesser curvature of the gastric body

C-3 – atrophy involves most of the lesser curvature of the gastric body, without reaching the cardia

O-1 – atrophy extends to the gastric body, reaching the cardia; the atrophy border lies between the lesser curvature and the anterior wall

O-2 – the atrophy border runs along the anterior wall of the gastric body

O-3 – atrophy involves almost the entire stomach; the border runs between the anterior wall and the greater curvature

Op – atrophic pangastritis

Endoscopic view corresponding to the Kimura-Takemoto classification of atrophic gastritis [23, 24]. The mucosal atrophy border (F-line) is indicated by the dashed line. A: C1; B: C2; C: C3; D: O1; E: O2; F: O3. Figure reproduced from [189] in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license.

Kyoto classification of gastritis [189]

Appendix B. Physician Action Algorithms

Figure 1.

Algorithm for the diagnosis and management of H. pylori infection in adults

Figure 2.

Management algorithm for patients with chronic gastritis with follow-up monitoring schedule

Appendix C. Patient Information

Currently, a microorganism known as Helicobacter pylori is recognized as the primary causative factor of gastritis. Therefore, every patient diagnosed with gastritis must be tested for this infection. If confirmed, treatment aimed at eliminating these bacteria (eradication) is required, followed by a follow-up test after 4-6 weeks. If the treatment fails, a repeat course of therapy with a different drug regimen should be prescribed. It is important to adhere to the treatment and strictly monitor medication intake. Eradication therapy leading to the elimination of Helicobacter pylori is now considered the primary measure aimed at healing the gastric mucosa and preventing gastric cancer. A family history of gastric cancer in close relatives (parents, grandparents) serves as an additional indication for anti-Helicobacter pylori treatment.