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

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

COVID­19 and post-COVID syndrome in the focus of complications: recommendations for physicians

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Efficacy of fecal microbiota transplantation in patients with post-infection irritable bowel syndrome with diarrhea

Objective — to evaluate efficacy of potentiation of remission and safety of fecal microbiota transplantation (TFM) in patients with post‑infection irritable bowel syndrome with predominance of diarrhea (PI — IBS‑D), in whom standard therapy was ineffective.&#x0D; Materials and methods. The study involved 16 patients with patients with moderate to severe PI — IBS with diarrhea who did not respond to standard therapy and did not have any significant comorbidities. The diagnosis of IBS was made according to the Rome IV criteria. IBS severity was assessed with the use of Irritable bowel syndrome — Severity Scoring System, and the frequency of defecation and stool consistency according to the Bristol scale. Donor selection, preparation for TFM and the procedure itself were carried out in accordance with the recommendations of the European Consensus on TFM (2017). TFM was performed once with a colonoscope in the right part of the large intestine — 180 ml of a solution prepared from 50 g of donor feces. The total follow‑up period was 6 months after TFM. Efficacy was assessed by the level of score reduction of the IBS‑SSS questionnaire — a decrease of 50 points or more was considered a significant improvement. During the observation period, the patient did not take any additional drugs and procedures.&#x0D; Results. The obtained results showed a positive TFM effects on the clinical manifestations of post‑infection IBS, resistant to standard therapy. After 1 month post transplantation, the severity of symptoms decreased by more than 75 IBS‑SSS points in 75 % of patients and 3 of them had remission. The TFM procedure resulted in a significant decrease compared to baseline in the severity of abdominal pain (37 points) and its duration (31 points), bloating (41 points), dissatisfaction with defecation (40 points) against the background of almost twofold reduction in the frequency of defecation from 3.68 to 1.81 bowel movements/day) and improved stool consistency according to the Bristol scale (from 6.81 to 5.21 points). These rates remained unchanged until the end of the third month after TFM, they did not differ significantly compared to the end of the first month: 75 % of patients experienced adequate relief of abdominal pain, satisfaction with defecation, reduced bloating and reduced impact on quality of life. However, by the end of 6th month, the symptoms of PI — IBS began to increase: the average score of IBS‑SSS increased to 169 points, including indicators of the intensity of abdominal pain and its duration, severity of bloating, dissatisfaction with defecation and defecation frequency, thus PI — IBS increasingly affected the quality of life of patients. Despite the increased PI — IBS severity by the end of 6th month after TFM, its symptoms remained significantly lower than before treatment and still 62.5 % of patients reported adequate relief of abdominal pain and satisfaction with defecation, reduction of diarrhea and bloating. None of patients reported about serious adverse events. During the first hours after procedure, only 31.25 % trial participants noticed insignificant adverse events (abdominal discomfort, flatulence and stomach growling) that disappeared on their own during the day.&#x0D; Conclusions. Colonoscopy‑delivered fecal microbiota transplantation proved to be effective and safe procedure in patients with PI — IBS who have not responded to standard therapy.&#x0D;  </jats:p

If drugs with metabolic action affect the intestinal microbiota. Literature review

The article presents the results of studies on humans showing the association between the use of specific drugs and changes in the microbial composition of the intestinal microbiome and its functional profile. It was found that the intestinal microbe directly or indirectly affects metabolism and effectiveness of a large number of drugs, causing variability in their activation, inactivation and toxicity. On the other hand, more than 800 non‑antibiotic drugs have also been shown to have significant effects on dozens of major species of bacteria that colonize the gastrointestinal tract. It is also noted that regardless of the route of administration, some drugs will spend considerable time in the intestine and contact the microbiome (parenterally administered drugs and their metabolites may enter the intestine through bile secretion), so the intestine is an important participant in drug metabolism. Data on the main taxonomic changes of PPI users are presented and it is shown that their severity was associated with higher doses of PPIs and that such changes in the microbiome may potentiate the development of diseases, as they are similar to those that reduce colonization resistance and intestinal infections. Much attention is paid to the presence of the association of intestinal microbiome — sugar‑lowering drugs. The data on the role of the intestinal microbiome as the main target of metformin are presented. In addition, metformin has been shown to increase Akkermansia muciniphila, which is known to be correlated with obesity, type 2 diabetes mellitus, cardiovascular diseases, and inflammation, and to increase lactobacilli in the upper small intestine, which will undoubtedly contribute to its antidiabetic effect. Metformin has been shown to regulate numerous metabolic pathways by interacting with the intestinal microbiota and partially eliminate dysbacteriosis caused by type 2 diabetes, and changes in the population of microorganisms that multiply with metformin are closely related to its efficacy and tolerability. With regard to other antidiabetic drugs (glitazones, alpha‑glucosidase inhibitors, DPP‑4 inhibitors, glucagon‑like peptide‑1 receptor agonists), it has also been shown that one of their main effects is the elimination of dysbacteriosis by including bacterial nutrient changes. and the length of stay of carbohydrates in the intestine, which also emphasizes their relationship with the intestinal microbiome. It is also noted that lactobacilli have inhibitory activity against DPP‑4 inhibitors. In this aspect, measures aimed at modifying the microbiome and especially probiotics, prebiotics and antibiotics may be of particular interest, as their use can significantly change the pharmacokinetics of drugs. It is noteworthy that the pattern of intestinal microbiome observed during treatment with liraglutide is the complete opposite of what is characteristic of the metabolic syndrome. The article shows that statin intake is also associated with changes in the intestinal microbiome and hypothesizes that the response of low‑density lipoprotein cholesterol to statins may be due to the activity of bacteria containing bile hydrolases. It is also noted that the intestinal microbiota can have a significant effect on the metabolism of psychoactive drugs by modulating intestinal permeability with subsequent effects on their absorption, and on the other hand taking this group of drugs leads to significant changes in intestinal microbiome. As a result, it is concluded that today it is very important and promising to study the interaction of intestinal microbiome and the most widely used drugs for the application of methods of modulation of intestinal microbiome to optimize the effectiveness of treatment of many diseases.&#x0D;  </jats:p

Intestinal permeability and its role in the pathogenesis and progress of non-alcoholic fatty liver disease. Review

Non‑alcoholic fatty liver disease (NAFLD) is a topical problem for the medicine worldwide, and its association with an «unhealthy» lifestyle and metabolic disorders is well established. The important role of dysbiosis of the intestinal microbiota in the NAFLD pathogenesis and the functioning of the intestine‑liver axis is emphasized. Data on the structure and functioning of the intestinal barrier in physiological conditions are presented. It has been proven that the presence of dysbiotic changes in the microbiota plays an important role in the disruption of the barrier function of the gastrointestinal tract, which in turn increases the level of physiological translocation of both bacteria and their toxins and their life products. Part of these harmful products comes to the liver through the portal vein (endotoxinemia). The antigens’ overload contributes to the development and progression of NAFLD (up to liver cirrhosis). The intestinal barrier is emphasized to be dynamic and sensitive to changes occurring in the intestine. The increased intestinal permeability and bacterial overgrowth syndrome (which is a source of increased endotoxemia) is observed in patients with NAFLD more frequently than in healthy subjects. Number of studies have revealed that the degree of intestinal permeability in NAFLD patients correlated with the steatosis severity. The factors that most significantly affect intestinal permeability in patients with NAFLD include microbial environment, bile acids, levels of fecal short‑chain fatty acids (mainly butyrate), the metabolism of the essential aromatic amino acid tryptophan, as well as the nature of nutrition, alcohol intake, medicinal preparations, stress, and level of physical activity, which act either directly or through the induction of intestinal microbiota dysbacteriosis. The increased intestinal permeability and its consequence — bacterial translocation, are noticed to be involved in the development of such complications as spontaneous bacterial peritonitis, hepatorenal syndrome, portal vein thrombosis, hepatic encephalopathy, hepatocellular carcinoma.&#x0D;  </jats:p