Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022.

BACKGROUND & AIMS: We aimed to assess the secular trend of the global prevalence of Helicobacter pylori (H pylori) infection in adults and children/adolescents and to show its relation to that of gastric cancer incidence. METHODS: We performed a systematic review and meta-analysis to calculate overall prevalence, adjusted by multivariate meta-regression analysis. The incidence rates of gastric cancer were derived from the Global Burden of Disease Study and Cancer Incidence in Five Continents. RESULTS: Of the 16,976 articles screened, 1748 articles from 111 countries were eligible for analysis. The crude global prevalence of H pylori has reduced from 52.6% (95% confidence interval [CI], 49.6%-55.6%) before 1990 to 43.9% (95% CI, 42.3%-45.5%) in adults during 2015 through 2022, but was as still as high as 35.1% (95% CI, 30.5%-40.1%) in children and adolescents during 2015 through 2022. Secular trend and multivariate regression analyses showed that the global prevalence of H pylori has declined by 15.9% (95% CI, -20.5% to -11.3%) over the last 3 decades in adults, but not in children and adolescents. Significant reduction of H pylori prevalence was observed in adults in the Western Pacific, Southeast Asian, and African regions. However, H pylori prevalence was not significantly reduced in children and adolescents in any World Health Organization regions. The incidence of gastric cancer has decreased globally and in various countries where the prevalence of H pylori infection has declined. CONCLUSIONS: The global prevalence of H pylori infection has declined during the last 3 decades in adults, but not in children and adolescents. The results raised the hypothesis that the public health drive to reduce the prevalence of H pylori as a strategy to reduce the incidence of gastric cancer in the population should be confirmed in large-scale clinical trials.

What defines a healthy gut microbiome?

The understanding that changes in microbiome composition can influence chronic human diseases and the efficiency of therapies has driven efforts to develop microbiota-centred therapies such as first and next generation probiotics, prebiotics and postbiotics, microbiota editing and faecal microbiota transplantation. Central to microbiome research is understanding how disease impacts microbiome composition and vice versa, yet there is a problematic issue with the term 'dysbiosis', which broadly links microbial imbalances to various chronic illnesses without precision or definition. Another significant issue in microbiome discussions is defining 'healthy individuals' to ascertain what characterises a healthy microbiome. This involves questioning who represents the healthiest segment of our population-whether it is those free from illnesses, athletes at peak performance, individuals living healthily through regular exercise and good nutrition or even elderly adults or centenarians who have been tested by time and achieved remarkable healthy longevity.This review advocates for delineating 'what defines a healthy microbiome?' by considering a broader range of factors related to human health and environmental influences on the microbiota. A healthy microbiome is undoubtedly linked to gut health. Nevertheless, it is very difficult to pinpoint a universally accepted definition of 'gut health' due to the complexities of measuring gut functionality besides the microbiota composition. We must take into account individual variabilities, the influence of diet, lifestyle, host and environmental factors. Moreover, the challenge in distinguishing causation from correlation between gut microbiome and overall health is presented.The review also highlights the resource-heavy nature of comprehensive gut health assessments, which hinders their practicality and broad application. Finally, we call for continued research and a nuanced approach to better understand the intricate and evolving concept of gut health, emphasising the need for more precise and inclusive definitions and methodologies in studying the microbiome.

RE.GA.IN.: the Real-world Gastritis Initiative-updating the updates.

At the end of the last century, a far-sighted 'working party' held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle.The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis.

The road to a world-unified approach to the management of patients with gastric intestinal metaplasia: a review of current guidelines.

OBJECTIVE: During the last decade, the management of gastric intestinal metaplasia (GIM) has been addressed by several distinct international evidence-based guidelines. In this review, we aimed to synthesise these guidelines and provide clinicians with a global perspective of the current recommendations for managing patients with GIM, as well as highlight evidence gaps that need to be addressed with future research. DESIGN: We conducted a systematic review of the literature for guidelines and consensus statements published between January 2010 and February 2023 that address the diagnosis and management of GIM. RESULTS: From 426 manuscripts identified, 16 guidelines were assessed. There was consistency across guidelines regarding the purpose of endoscopic surveillance of GIM, which is to identify prevalent neoplastic lesions and stage gastric preneoplastic conditions. The guidelines also agreed that only patients with high-risk GIM phenotypes (eg, corpus-extended GIM, OLGIM stages III/IV, incomplete GIM subtype), persistent refractory Helicobacter pylori infection or first-degree family history of gastric cancer should undergo regular-interval endoscopic surveillance. In contrast, low-risk phenotypes, which comprise most patients with GIM, do not require surveillance. Not all guidelines are aligned on histological staging systems. If surveillance is indicated, most guidelines recommend a 3-year interval, but there is some variability. All guidelines recommend H. pylori eradication as the only non-endoscopic intervention for gastric cancer prevention, while some offer additional recommendations regarding lifestyle modifications. While most guidelines allude to the importance of high-quality endoscopy for endoscopic surveillance, few detail important metrics apart from stating that a systematic gastric biopsy protocol should be followed. Notably, most guidelines comment on the role of endoscopy for gastric cancer screening and detection of gastric precancerous conditions, but with high heterogeneity, limited guidance regarding implementation, and lack of robust evidence. CONCLUSION: Despite heterogeneous populations and practices, international guidelines are generally aligned on the importance of GIM as a precancerous condition and the need for a risk-stratified approach to endoscopic surveillance, as well as H. pylori eradication when present. There is room for harmonisation of guidelines regarding (1) which populations merit index endoscopic screening for gastric cancer and GIM detection/staging; (2) objective metrics for high-quality endoscopy; (3) consensus on the need for histological staging and (4) non-endoscopic interventions for gastric cancer prevention apart from H. pylori eradication alone. Robust studies, ideally in the form of randomised trials, are needed to bridge the ample evidence gaps that exist.

Role of the Gut Microbiome in Metabolic dysfunction-Associated Steatotic Liver Disease.

The prevalence of Metabolic dysfunction-associated steatotic liver disease (MASLD) - previously described as non-alcoholic fatty liver disease (NAFLD) - continues to rise globally. Despite this, therapeutic measures for MASLD remain limited. Recently, there has been a growing interest in the gut microbiome's role in the pathogenesis of MASLD. Understanding this relationship may allow for the administration of therapeutics that target the gut microbiome and/or its metabolic function to alleviate MASLD development or progression. This review will discuss the interplay between the gut microbiome's structure and function in relation to the development of MASLD, assess the diagnostic yield of gut microbiome-based signatures as a non-invasive tool to identify MASLD severity, and examine current and emerging therapies targeting the gut microbiome-liver axis.

Oral, Vaginal, and Stool Microbial Signatures in Patients With Endometriosis as Potential Diagnostic Non-Invasive Biomarkers: A Prospective Cohort Study.

OBJECTIVE: To identify a microbial signature for endometriosis for use as a diagnostic non-invasive biomarker. DESIGN: Prospective cohort pilot study. SETTING: Nepean Hospital and UNSW Microbiome Research Centre, Australia. POPULATION: Sixty-four age- and sex-matched subjects (n = 19 healthy control (HC); n = 24 non-endometriosis (N-ENDO) and n = 21 confirmed endometriosis (ENDO)). All study participants, besides healthy controls, underwent laparoscopic surgical assessment for endometriosis, and histology was performed on excised lesions. METHODS: Oral, stool and, vaginal samples were self-collected at a single time point for healthy controls, and preoperatively for patients undergoing laparoscopy. Samples underwent 16S rRNA amplicon sequencing, followed by bioinformatics analysis. MAIN OUTCOME MEASURES: Compositional differences between cohorts as identified by diversity analyses, and differentially abundant microbial taxa, as identified by LEfSE analysis. RESULTS: The composition of the oral (adjusted p = 0.003), and stool (adjusted p = 0.042) microbiota is different between the three cohorts. Differentially abundant taxa are present within each cohort as identified by LEfSE analysis. Particularly, Fusobacterium was enriched in the oral samples of patients with moderate/severe endometriosis. CONCLUSIONS: Taxonomic and compositional differences were found between the microbiota in the mouth, gut and, vagina of patients with and without endometriosis and healthy controls. Fusobacterium was enriched in patients with moderate/severe endometriosis. Fusobacterium is noted as a key pathogen in periodontal disease, a common comorbidity in endometriosis. These findings suggest a role for the oral, stool and, vaginal microbiome in endometriosis, and present potential for microbial-based treatments and the design of a diagnostic swab.

Perturbations in gut microbiota composition in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: The results of human observational studies on the correlation between gut microbiota perturbations and polycystic ovary syndrome (PCOS) have been contradictory. This study aimed to perform the first systematic review and meta-analysis to evaluate the specificity of the gut microbiota in PCOS patients compared to healthy women. METHODS: Literature through May 22, 2023, was searched on PubMed, Web of Science, Medline, Embase, Cochrane Library, and Wiley Online Library databases. Unreported data in diversity indices were filled by downloading and processing raw sequencing data. Systematic review inclusion: original studies were eligible if they applied an observational case-control design, performed gut microbiota analysis and reported diversity or abundance measures, sampled general pre-menopausal women with PCOS, and are longitudinal studies with baseline comparison between PCOS patients and healthy females. Systematic review exclusion: studies that conducted interventional or longitudinal comparisons in the absence of a control group. Two researchers made abstract, full-text, and data extraction decisions, independently. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodologic quality. Hedge's g standardized mean difference (SMD), confidence intervals (CIs), and heterogeneity (I2) for alpha diversity were calculated. Qualitative syntheses of beta-diversity and microbe alterations were performed. RESULTS: Twenty-eight studies (n = 1022 patients, n = 928 control) that investigated gut microbiota by collecting stool samples were included, with 26 and 27 studies having provided alpha-diversity and beta-diversity results respectively. A significant decrease in microbial evenness and phylogenetic diversity was observed in PCOS patients when compared with control participants (Shannon index: SMD = - 0.27; 95% CI, - 0.37 to - 0.16; phylogenetic diversity: SMD = - 0.39; 95% CI, -- 0.74 to - 0.03). We also found that reported beta-diversity was inconsistent between studies. Despite heterogeneity in bacterial relative abundance, we observed depletion of Lachnospira and Prevotella and enrichment of Bacteroides, Parabacteroides, Lactobacillus, Fusobacterium, and Escherichia/Shigella in PCOS. Gut dysbiosis in PCOS, which might be characterized by the reduction of short-chain fatty acid (SCFA)-producing and bile-acid-metabolizing bacteria, suggests a shift in balance to favor pro-inflammatory rather than anti-inflammatory bacteria. CONCLUSIONS: Gut dysbiosis in PCOS is associated with decreased diversity and alterations in bacteria involved in microbiota-host crosstalk. TRIAL REGISTRATION: PROSPERO registration: CRD42021285206, May 22, 2023.

A Novel Bifidobacterium/Klebsiella Ratio in Characterization Analysis of the Gut and Bile Microbiota of CCA Patients.

Cholangiocarcinoma (CCA) is a serious health problem worldwide. The gut and bile microbiota have not been clearly characterized in patients with CCA, and better noninvasive diagnostic approaches for CCA need to be established. The aim of this study was to investigate the characteristics of the gut and bile microbiota in CCA patients. Forty-two CCA patients and 16 healthy normal controls (HNCs) were enrolled. DNA was extracted from fecal and bile samples and subjected to 16S rRNA gene analysis. We found that there were significant differences in the species diversity, structure, and composition of the microbial communities between the CCA group and the HNC grouAt the phylum level, compared with that in the HNC group, the relative abundance of Firmicutes and Actinobacteriota was significantly decreased in the CCA group, whereas Proteobacteria and Bacteroidota were significantly enriched. The Firmicutes/Bacteroidota (F/B) ratio significantly decreased in the CCA group compared to the HNC grouThe relative abundance of Klebsiella in the CCA group was significantly higher than that in the HNC group, while the relative abundance of Bifidobacterium was significantly decreased. The Bifidobacterium/Klebsiella (B/K) ratio was established as a novel biomarker and was found to be significantly decreased in the CCA group compared with the HNC grouOur findings provide evidence supporting the use of Klebsiella and Bifidobacterium as noninvasive intestinal microbiomarkers for improving the diagnosis of CCA.

Liver-specific deletion of miR-181ab1 reduces liver tumour progression via upregulation of CBX7.

MiR-181 expression levels increased in hepatocellular carcinoma (HCC) compared to non-cancerous tissues. MiR-181 has been widely reported as a possible driver of tumourigenesis but also acts as a tumour suppressor. In addition, the miR-181 family regulates the development and function of immune and vascular cells, which play vital roles in the progression of tumours. More complicatedly, many genes have been identified as miR-181 targets to mediate the effects of miR-181. However, the role of miR-181 in the development of primary tumours remains largely unexplored. We aimed to examine the function of miR-181 and its vital mediators in the progression of diethylnitrosamine-induced primary liver cancers in mice. The size of liver tumours was significantly reduced by 90% in global (GKO) or liver-specific (LKO) 181ab1 knockout mice but not in hematopoietic and endothelial lineage-specific knockout mice, compared to WT mice. In addition, the number of tumours was significantly reduced by 50% in GKO mice. Whole-genome RNA-seq analysis and immunohistochemistry showed that epithelial-mesenchymal transition was partially reversed in GKO tumours compared to WT tumours. The expression of CBX7, a confirmed miR-181 target, was up-regulated in GKO compared to WT tumours. Stable CBX7 expression was achieved with an AAV/Transposase Hybrid-Vector System and up-regulated CBX7 expression inhibited liver tumour progression in WT mice. Hepatic CBX7 deletion restored the progression of LKO liver tumours. MiR-181a expression was the lowest and CBX7 expression the highest in iClust2 and 3 subclasses of human HCC compared to iClust1. Gene expression profiles of GKO tumours overlapped with low-proliferative peri-portal-type HCCs. Liver-specific loss of miR-181ab1 inhibited primary liver tumour progression via up-regulating CBX7 expression, but tumour induction requires both hepatic and non-hepatic miR-181. Also, miR-181ab1-deficient liver tumours may resemble low-proliferative periportal-type human HCC. miR-181 was increased with liver tumour growth. More miR-181, darker colour and higher shape. CBX7 was very low in pericentral hepatocytes, increased in early liver tumours, but reduced in advanced liver tumours. Its levels were maintained in miR-181 KO liver tumours. In tumours (T), brown (darker is more) represents miR-181, the blue circle (thicker is more) represents CBX7.

Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report.

Helicobacter pyloriInfection is formally recognised as an infectious disease, an entity that is now included in the International Classification of Diseases 11th Revision. This in principle leads to the recommendation that all infected patients should receive treatment. In the context of the wide clinical spectrum associated with Helicobacter pylori gastritis, specific issues persist and require regular updates for optimised management.The identification of distinct clinical scenarios, proper testing and adoption of effective strategies for prevention of gastric cancer and other complications are addressed. H. pylori treatment is challenged by the continuously rising antibiotic resistance and demands for susceptibility testing with consideration of novel molecular technologies and careful selection of first line and rescue therapies. The role of H. pylori and antibiotic therapies and their impact on the gut microbiota are also considered.Progress made in the management of H. pylori infection is covered in the present sixth edition of the Maastricht/Florence 2021 Consensus Report, key aspects related to the clinical role of H. pylori infection were re-evaluated and updated. Forty-one experts from 29 countries representing a global community, examined the new data related to H. pylori infection in five working groups: (1) indications/associations, (2) diagnosis, (3) treatment, (4) prevention/gastric cancer and (5) H. pylori and the gut microbiota. The results of the individual working groups were presented for a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in various clinical fields.

Kyoto international consensus report on anatomy, pathophysiology and clinical significance of the gastro-oesophageal junction.

OBJECTIVE: An international meeting was organised to develop consensus on (1) the landmarks to define the gastro-oesophageal junction (GOJ), (2) the occurrence and pathophysiological significance of the cardiac gland, (3) the definition of the gastro-oesophageal junctional zone (GOJZ) and (4) the causes of inflammation, metaplasia and neoplasia occurring in the GOJZ. DESIGN: Clinical questions relevant to the afore-mentioned major issues were drafted for which expert panels formulated relevant statements and textural explanations.A Delphi method using an anonymous system was employed to develop the consensus, the level of which was predefined as ≥80% of agreement. Two rounds of voting and amendments were completed before the meeting at which clinical questions and consensus were finalised. RESULTS: Twenty eight clinical questions and statements were finalised after extensive amendments. Critical consensus was achieved: (1) definition for the GOJ, (2) definition of the GOJZ spanning 1 cm proximal and distal to the GOJ as defined by the end of palisade vessels was accepted based on the anatomical distribution of cardiac type gland, (3) chemical and bacterial (Helicobacter pylori) factors as the primary causes of inflammation, metaplasia and neoplasia occurring in the GOJZ, (4) a new definition of Barrett's oesophagus (BO). CONCLUSIONS: This international consensus on the new definitions of BO, GOJ and the GOJZ will be instrumental in future studies aiming to resolve many issues on this important anatomic area and hopefully will lead to better classification and management of the diseases surrounding the GOJ.

J-Edited DIffusional Proton Nuclear Magnetic Resonance Spectroscopic Measurement of Glycoprotein and Supramolecular Phospholipid Biomarkers of Inflammation in Human Serum.

Proton nuclear magnetic resonance (NMR) N-acetyl signals (Glyc) from glycoproteins and supramolecular phospholipids composite peak (SPC) from phospholipid quaternary nitrogen methyls in subcompartments of lipoprotein particles) can give important systemic metabolic information, but their absolute quantification is compromised by overlap with interfering resonances from lipoprotein lipids themselves. We present a J-Edited DIffusional (JEDI) proton NMR spectroscopic approach to selectively augment signals from the inflammatory marker peaks Glyc and SPCs in blood serum NMR spectra, which enables direct integration of peaks associated with molecules found in specific compartments. We explore a range of pulse sequences that allow editing based on peak J-modulation, translational diffusion, and T2 relaxation time and validate them for untreated blood serum samples from SARS-CoV-2 infected patients (n = 116) as well as samples from healthy controls and pregnant women with physiological inflammation and hyperlipidemia (n = 631). The data show that JEDI is an improved approach to selectively investigate inflammatory signals in serum and may have widespread diagnostic applicability to disease states associated with systemic inflammation.

Aspirin Reduces Colorectal Tumor Development in Mice and Gut Microbes Reduce its Bioavailability and Chemopreventive Effects.

BACKGROUND & AIMS: Alterations in the intestinal microbiota affect development of colorectal cancer and drug metabolism. We studied whether the intestinal microbiota affect the ability of aspirin to reduce colon tumor development in mice. METHODS: We performed studies with APCmin/+ mice and mice given azoxymethane and dextran sulfate sodium to induce colorectal carcinogenesis. Some mice were given antibiotics to deplete intestinal microbes, with or without aspirin, throughout the entire experiment. Germ-free mice were studied in validation experiments. Colon tissues were collected and analyzed by histopathology, quantitative reverse-transcription polymerase chain reaction, and immunoblots. Blood samples and gut luminal contents were analyzed by liquid chromatography/mass spectrometry and an arylesterase activity assay. Fecal samples were analyzed by 16S ribosomal RNA gene and shotgun metagenome sequencing. RESULTS: Administration of aspirin to mice reduced colorectal tumor number and load in APCmin/+ mice and mice given azoxymethane and dextran sulfate sodium that had been given antibiotics (depleted gut microbiota), but not in mice with intact microbiota. Germ-free mice given aspirin developed fewer colorectal tumors than conventionalized germ-free mice given aspirin. Plasma levels of aspirin were higher in mice given antibiotics than in mice with intact gut microbiota. Analyses of luminal contents revealed that aerobic gut microbes, including Lysinibacillus sphaericus, degrade aspirin. Germ-free mice fed L sphaericus had lower plasma levels of aspirin than germ-free mice that were not fed this bacterium. There was an inverse correlation between aspirin dose and colorectal tumor development in conventional mice, but this correlation was lost with increased abundance of L sphaericus. Fecal samples from mice fed aspirin were enriched in Bifidobacterium and Lactobacillus genera, which are considered beneficial, and had reductions in Alistipes finegoldii and Bacteroides fragili, which are considered pathogenic. CONCLUSIONS: Aspirin reduces development of colorectal tumors in APCmin/+ mice and mice given azoxymethane and dextran sulfate sodium, depending on the presence of intestinal microbes. L sphaericus in the gut degrades aspirin and reduced its chemopreventive effects in mice. Fecal samples from mice fed aspirin were enriched in beneficial bacteria, with reductions in pathogenic bacteria.

Impact of diet and the bacterial microbiome on the mucous barrier and immune disorders.

The prevalence of chronic immune and metabolic disorders is increasing rapidly. In particular, inflammatory bowel diseases, obesity, diabetes, asthma and chronic obstructive pulmonary disease have become major healthcare and economic burdens worldwide. Recent advances in microbiome research have led to significant discoveries of associative links between alterations in the microbiome and health, as well as these chronic supposedly noncommunicable, immune/metabolic disorders. Importantly, the interplay between diet, microbiome and the mucous barrier in these diseases has gained significant attention. Diet modulates the mucous barrier via alterations in gut microbiota, resulting in either disease onset/exacerbation due to a "poor" diet or protection against disease with a "healthy" diet. In addition, many mucosa-associated disorders possess a specific gut microbiome fingerprint associated with the composition of the mucous barrier, which is further influenced by host-microbiome and inter-microbial interactions, dietary choices, microbe immigration and antimicrobials. Our review focuses on the interactions of diet (macronutrients and micronutrients), gut microbiota and mucous barriers (gastrointestinal and respiratory tract) and their importance in the onset and/or progression of major immune/metabolic disorders. We also highlight the key mechanisms that could be targeted therapeutically to prevent and/or treat these disorders.

Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus.

OBJECTIVE: A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC). METHODS: 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed. RESULTS: Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of 'the point of no return'. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori. CONCLUSION: Evidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori. Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.

Efficacies of Genotypic Resistance-Guided vs Empirical Therapy for Refractory Helicobacter pylori Infection.

BACKGROUND & AIMS: We aimed to compare the efficacy of genotypic resistance-guided therapy vs empirical therapy for eradication of refractory Helicobacter pylori infection in randomized controlled trials. METHODS: We performed 2 multicenter, open-label trials of patients with H pylori infection (20 years or older) failed by 2 or more previous treatment regimens, from October 2012 through September 2017 in Taiwan. The patients were randomly assigned to groups given genotypic resistance-guided therapy for 14 days (n = 21 in trial 1, n = 205 in trial 2) or empirical therapy according to medication history for 14 days (n = 20 in trial 1, n = 205 in trial 2). Patients received sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole, with levofloxacin, clarithromycin, or tetracycline (doxycycline in trial 1, tetracycline in trial 2) for another 7 days (all given twice daily) based on genotype markers of resistance determined from gastric biopsy specimens (group A) or empirical therapy according to medication history. Resistance-associated mutations in 23S ribosomal RNA or gyrase A were identified by polymerase chain reaction with direct sequencing. Eradication status was determined by 13C-urea breath test. The primary outcome was eradication rate. RESULTS: H pylori infection was eradicated in 17 of 21 (81%) patients receiving genotype resistance-guided therapy and 12 of 20 (60%) patients receiving empirical therapy (P = .181) in trial 1. This trial was terminated ahead of schedule due to the low rate of eradication in patients given doxycycline sequential therapy (15 of 26 [57.7%]). In trial 2, H pylori infection was eradicated in 160 of 205 (78%) patients receiving genotype resistance-guided therapy and 148 of 205 (72.2%) patients receiving empirical therapy (P = .170), according to intent to treat analysis. The frequencies of adverse effects and compliance did not differ significantly between groups. CONCLUSIONS: Properly designed empirical therapy, based on medication history, is an acceptable alternative to genotypic resistance-guided therapy for eradication of refractory H pylori infection after consideration of accessibility, cost, and patient preference. ClinicalTrials.gov ID: NCT01725906.