Helicobacter pylori Diagnostic Tests Used in Europe: Results of over 34,000 Patients from the European Registry on Helicobacter pylori Management

Background and aims: Several methods are available to diagnose Helicobacter pylori infection. Our objective was to evaluate the tests used for both the initial diagnosis and the confirmation of eradication after treatment in Europe. Methods: The European Registry on the management of Helicobacter pylori infection is an international, multicentre, prospective, non-interventional registry aiming to evaluate the management of Helicobacter pylori-infected patients in Europe. Countries with at least 100 cases registered from June 2013 to April 2021, and with a validated diagnostic method were analysed. Data were quality reviewed. Results: A total of 34,920 adult patients from 20 countries were included (mean age 51 years; 61% women). To establish the initial diagnosis, invasive tests were performed in 19,801 (71%) patients, non-invasive in 11,369 (41%), and both in 3437 (12%). The most frequent were histology (n = 11,885; 43%), a rapid urease test (n = 10,636; 38%) and an urea breath test (n = 7577; 27%). According to the age, invasive tests were indicated in 11,179 (77%) ≥50 years, and in 8603 (65%) <50 years. Depending on the country, the use of invasive tests ranged from 29–99% in <50 years to 60–99% in ≥50. Most of the tests used to confirm eradication were non-invasive (n = 32,540; 93%), with the urea breath test being the most frequent (n = 32,540; 78%). In 2983 (9%) post-treatment tests, histology (n = 1887; 5%) or a rapid urease test (n = 1223; 4%) were performed. Conclusion: A great heterogeneity was observed for the initial diagnosis and confirmation of the eradication. The reasons for the apparent lack of adherence to the clinical guidelines should be further explored

Analysis of Clinical Phenotypes through Machine Learning of First-Line H. pylori Treatment in Europe during the Period 2013–2022: Data from the European Registry on H. pylori Management (Hp-EuReg)

The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection: All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the “most important” variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013–2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin–clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth–quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin–amoxicillin–metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year

Comparison of the management of Helicobacter pylori infection between the older and younger European populations

The prevalence of Helicobacter pylori remains high in the older population. Specific age-related peculiarities may impact the outcomes of H. pylori treatment. The aim of the study was to evaluate the diagnostics and effectiveness of H. pylori eradication between the younger and older European populations. “European Registry on H. pylori Management (Hp-EuReg)” data from 2013 to 2022 were analyzed. Patients were divided into older (≥ 60 years) and younger (18–59 years) groups. Modified intention-to-treat (mITT) and per-protocol (PP) analysis was performed. 49,461 patients included of which 14,467 (29%) were older-aged. Concomitant medications and penicillin allergy were more frequent among the older patients. Differences between younger and older populations were observed in treatment duration in first-line treatment and in proton pump inhibitors (PPIs) doses in second-line treatment. The overall incidence of adverse events was lower in the older adults group. The overall first-line treatment mITT effectiveness was 88% in younger and 90% in the older patients (p < 0.05). The overall second-line mITT treatment effectiveness was 84% in both groups. The effectiveness of the most frequent first- and second-line triple therapies was suboptimal (< 90%) in both groups. Optimal efficacy (≥ 90%) was achieved by using bismuth and non-bismuth-based quadruple therapies. In conclusion, the approach to the diagnostics and treatment of H. pylori infection did not generally differ between younger and older patients. Main differences were reported in the concurrent medications, allergy to penicillin and adverse events both in first- and second-line treatment. Optimal effectiveness rates were mostly achieved by using bismuth and non-bismuth-based quadruple therapies. No clinically relevant differences in the effectiveness between the age groups were observed

Role of compliance in Helicobacter pylori eradication treatment: Results of the European Registry on H. pylori management

Background: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy. Objective: To determine which factors influence compliance with treatment. Methods: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance. Results: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2–7.7]; p < 0.001). Conclusions: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication

Evolution of the use, effectiveness and safety of bismuth-containing quadruple therapy for Helicobacter pylori infection between 2013 and 2021: results from the European registry on H. pylori management (Hp-EuReg)

background Bismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of high bacterial antibiotic resistance. Objective To describe the time trends of use, effectiveness and safety of BQT in Europe using the European Registry on Helicobacter pylori Management (Hp-EuReg). Design Patients registered in the Hp-EuReg from 2013 to 2021 who had received BQT were included. The regimens prescribed, the number of eradication attempts, effectiveness, adherence and safety were analysed. The effectiveness was assessed by modified intention to treat (mITT). Time-trend and multivariate analyses were performed to determine variables that predicted treatment success. results Of the 49 690 patients included in the Hp-EuReg, 15 582 (31%) had received BQT. BQT use increased from 8.6% of all treatments in 2013 to 39% in 2021. Single-capsule BQT—containing bismuth, metronidazole and tetracycline—plus a PPI (single-capsule BQT, ScBQT) was the most frequent treatment mode (43%). Schemes that obtained an effectiveness above 90% were the 10-day ScBQT and 14-day BQT using tetracycline plus metronidazole, or amoxicillin plus either clarithromycin or metronidazole. Only ScBQT achieved above 90% cure rates in all the geographical areas studied. Using the ScBQT scheme, adherence, the use of standard or high-dose PPIs, 14-day prescriptions and the use of BQT as first-line treatment were significantly associated with higher mITT effectiveness. Conclusion The use of BQT increased notably in Europe over the study period. A 10-day ScBQT was the scheme that most consistently achieved optimal effectiveness

A standardised model for stool banking for faecal microbiota transplantation: a consensus report from a multidisciplinary UEG working group

Background Faecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of faeces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council.Objective Several European and international consensus statements concerning faecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document.Methods Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about faecal microbiota transplantation.Results A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening.Conclusion The implementation of faecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor faeces preparations for patients.Molecular basis of bacterial pathogenesis, virulence factors and antibiotic resistanc

Синдром обструктивного апное/гіпопное сну та неалкогольна жирова хвороба печінки: роль гіпоксії

Sleep disorders is one of the topical issues of our times, affecting about half of the adult population. It has been determined that the most common sleep problems are obstructive sleep apnea/hypopnea syndrome — according to the WHO, its prevalence is comparable to the prevalence of diabetes. The data on the prevalence of obstructive sleep apnea/hypopnea syndrome in patients with metabolic syndrome are presented. Attention is drawn to the importance of overweight and obesity in the occurrence of obstructive sleep apnea/hypopnea syndrome and their relationship with the severity of the latter. The main mechanisms of obstructive sleep apnea/hypopnea sleep syndrome in obesity and the main links in the pathogenesis of progression of non-alcoholic fatty liver disease are described. The role of oxidative stress in the occurrence of inflammation and liver fibrosis is emphasized. The role of hypoxia in the pathogenesis of progression of nonalcoholic fatty liver disease in its combination with obstructive sleep apnea/hypopnea syndrome and its correlation with inflammatory and fibrosing processes has been shown. The unique place of a liver in a homeostasis of oxygen in an organism is noted. The history of the discovery and distribution of the family of hypoxia-induced factors is described. It is emphasized that all alpha subunits of the GIF complex act simultaneously, affecting both common and different molecular targets, which causes their special biological effects. The role of hypoxia-induced factors in the regulation of various processes in the body is shown. The advantage of studying hypoxia-induced factor-2a in the combined course of obstructive sleep apnea/hypopnea syndrome and non-alcoholic fatty liver disease is substantiated. The role of hypoxia-induced factor-2 alpha in the development and progression of nonalcoholic fatty liver disease has been shown.Нарушения сна являются актуальной проблемой современности, поскольку касаются около половины взрослого населения. Установлено, что одной из наиболее распространенных проблем сна является синдром обструктивного апноэ/гипопноэ сна. По данным ВОЗ, его распространенность сопоставима с таковой сахарного диабета. Приведены данные о распространенности синдрома обструктивного апноэ/гипопноэ сна у пациентов с метаболическим синдромом. Обращено внимание на значимость избыточной массы тела и ожирения в возникновении синдрома обструктивного апноэ/гипопноэ сна и их связь с тяжестью течения последнего. Описаны механизмы возникновения синдрома обструктивного апноэ/гипопноэ сна при ожирении и основные звенья патогенеза прогрессирования неалкогольной жировой болезни печени. Подчеркнуто значение оксидантного стресса в возникновении воспаления и фиброза печени. Показана роль гипоксии в патогенезе прогрессирования неалкогольной жировой болезни печени при ее сочетании с синдромом обструктивного апноэ/гипопноэ сна и его связь с воспалительными и фиброзирующими процессами. Печень имеет важное значение в гомеостазе кислорода в организме. Описана история открытия семейства индуцированных гипоксией факторов. Подчеркнуто, что все α-субъединицы комплекса индуцированных гипоксией факторов действуют одновременно, поражая как общие, так и разные молекулярные цели, что обуславливает их особые биологические эффекты. Показана роль индуцированных гипоксией факторов в регулировании разных процессов в организме. Обосновано преимущество изучения индуцированного гипоксией фактора-2α при совместном течении синдрома обструктивного апноэ/гипопноэ сна и неалкогольной жировой болезни печени. Показана роль индуцированного гипоксией фактора-2α в развитии и прогрессировании неалкогольной жировой болезни печени.Порушення сну є актуальною проблемою сьогодення, оскільки стосуються близько половини дорослого населення. Встановлено, що однією з найпоширеніших проблем сну є синдром обструктивного апное/гіпопное сну. За даними ВООЗ, його поширеність порівнянна з такою цукрового діабету. Наведено дані про поширеність синдрому обструктивного апное/гіпопное сну у пацієнтів з метаболічним синдромом. Звернуто увагу на значущість надлишкової маси тіла та ожиріння у виникненні синдрому обструктивного апное/гіпопное сну та їх зв’язок з тяжкістю перебігу останнього. Описано механізми виникнення синдрому обструктивного апное/гіпопное сну при ожирінні та основні ланки патогенезу прогресування неалкогольної жирової хвороби печінки. Наголошено на значенні оксидантного стресу у виникненні запалення і фіброзу печінки. Показано роль гіпоксії в патогенезі прогресування неалкогольної жирової хвороби печінки при її поєднанні із синдромом обструктивного апное/гіпопное сну і його зв’язок із запальними та фіброзними процесами. Печінка має важливе значення в гомеостазі кисню в організмі. Описано історію відкриття сімейства індукованих гіпоксією факторів. Наголошено, що всі α-субодиниці комплексу індукованих гіпоксією факторів діють одночасно, вражаючи як загальні, так і різні молекулярні цілі, що зумовлює їх особливі біологічні ефекти. Показано роль індукованих гіпоксією факторів у регулюванні різних процесів в організмі. Обґрунтовано перевагу вивчення індукованого гіпоксією фактора-2α при спільному перебігу синдрому обструктивного апное/гіпопное сну і неалкогольної жирової хвороби печінки. Показано роль індукованого гіпоксією фактора-2α в розвитку і прогресуванні неалкогольної жирової хвороби печінки

Main phylotypes of gut microbiota and their connection with the degree of obesity and the stage of liver fibrosis in patients with non-alcoholic fatty liver disease

Objective — to analyse the state of the relative composition of gut microbiota (GM) at the level of the main phylotypes in patients with non‑alcoholic fatty liver disease (NAFLD) with different body mass index and degree of liver fibrosis.&#x0D; Materials and methods. The study involved 105 people. The main group consisted of 85 patients with NAFLD with obesity of 36.50 [32.00; 40.60] kg/m2, who were divided into three subgroups depending on the degree of obesity. Subgroup I included 38 patients who were diagnosed with the first degree of obesity. Subgroup II included 23 patients diagnosed with the second degree. Subgroup III consisted of 24 patients with the third degree of obesity. The control group consisted of 20 practically healthy individuals 23.50 [21.35; 25.78] kg/m2. Determination of the degree of fibrosis according to METAVIR scale by measuring the average stiffness of the liver parenchyma in the mode of shear wave elastography. The composition of GM at the level of the main phylotypes was studied by identifying total bacterial DNA and DNA of Bacteroidetes, Firmicutes, as well as Firmicutes/Bacteroidetes ratio by quantitative real‑time polymerase chain reaction using universal primers for the 16S rRNA gene and taxon‑specific primers. Statistical processing was performed using Statistica 13.1.&#x0D; Results. In the comorbid course of NAFLD and the first degree of obesity, 47.37 % of patients had no signs of fibrosis and the same number were diagnosed with F1 fibrosis, two patients (5.26 %) had F2 fibrosis, and F3 fibrosis was not diagnosed in any patient. In subgroup II, two‑thirds actually had liver fibrosis, but F3 fibrosis was not detected in any patient. In patients of subgroup III, only 20.83 % of patients had no signs of liver fibrosis, while 37.50 % were diagnosed with F1 fibrosis, 33.33 % with F2 fibrosis, and 8.33 % with F3 fibrosis. In other words, the most severe F3 fibrosis was observed in patients with the third degree of obesity. In patients of the subgroup I, the statistically significant increase in the relative ratio of Firmicutes/Bacteroidetes was found compared to the control group: 3.07 times (p &lt; 0.01) in the absence of fibrosis and already in the presence of the 1st stage of fibrosis this indicator increased to 3.21 (p &lt; 0.01), while in the 2nd stage it increased almost 4 times (p &lt; 0.01). However, when comparing this indicator in the first subgroup between the stages of fibrosis, no statistically significant deviations were found (p &gt; 0.05), i.e., the changes were only tendency‑like. In patients of the subgroup II, the statistically significant increase in the relative ratio of Firmicutes/Bacteroidetes was also found compared to the control group: 3.25 times (p &lt; 0.01) in the absence of fibrosis, 3.81 times (p &lt; 0.01) in the 1st stage of fibrosis, 5.08 times (p &lt; 0.01) in the 2nd stage of fibrosis, which was the maximum value. Also, the statistically significant increase in the relative ratio of Firmicutes/Bacteroidetes by 1.57 times (p &lt; 0.01) was found at F2 compared to F0, while between other stages of fibrosis, the changes were trending and had no statistically significant differences. In patients of subgroup III in the absence of fibrosis, the relative ratio of Firmicutes/Bacteroidetes also exceeded that of the control group and progressively increased with increasing fibrosis. It should be noted that the statistically significant increase in the relative ratio of Firmicutes/Bacteroidetes between F2 and F0 by 1.28 times (p &lt; 0.01) and between F3 and F0 by 1.35 times (p &lt; 0.01) was found.&#x0D; Conclusions. When analysing the relative composition of GM in the studied subgroups depending on the stage of fibrosis, it was found that the increase in the stage of liver fibrosis is associated with certain disorders of Firmicutes/Bacteroidetes ratio, the relative content of Firmicutes and Bacteroidetes. Thus, in the subgroup I, the relative composition of GM significantly differed only from the control group, while in patients of the subgroup II with F2 fibrosis there was the statistically significant increase in the relative ratio of Firmicutes/Bacteroidetes by more than one and a half times compared to patients without signs of fibrosis. At the same time, in patients of the subgroup III with fibrosis, not only F2, but also F3, the statistically significant increase in the relative ratio of Firmicutes/Bacteroidetes was found.&#x0D;  </jats:p