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Infection Apr 2024More than half of the world's population are colonized with H. pylori; however, the prevalence varies geographically with the highest incidence in Africa. H. pylori is... (Review)
Review
More than half of the world's population are colonized with H. pylori; however, the prevalence varies geographically with the highest incidence in Africa. H. pylori is probably a commensal organism that has been associated with the development of gastritis, ulcers, and gastric cancer. H. pylori alone is most probably not enough for the development of gastric carcinoma, but evidence for its association with the disease is high and has, therefore, been classified by the International Agency for Research on Cancer as a Class 1 carcinogen. Bacteroidetes and Fusobacteria positively coexisted during H. pylori infection along the oral-gut axis. The eradication therapy required to treat H. pylori infection can also have detrimental consequences for the gut microbiota, leading to a decreased alpha diversity. Therefore, therapy regimens integrated with probiotics may abolish the negative effects of antibiotic therapy on the gut microbiota. These eradication therapies combined with probiotics have also higher rates of eradication, when compared to standard treatments, and are associated with reduced side effects, improving the patient's compliance. The eradication therapy not only affects gut microbiome but also affects the oral microbiome with robust predominance of harmful bacteria. However, there have been reports of a protective role of H. pylori in Barrett's esophagus, esophageal adenocarcinoma, eosinophilic esophagitis, IBD, asthma, and even multiple sclerosis. Therefore, eradication therapy should be carefully considered, and test to treat policy should be tailored to specific communities especially in highly endemic areas. Supplementation of probiotics, prebiotics, herbals, and microbial metabolites to reduce the negative effects of eradication therapy should be considered. After failure of many eradication attempts, the benefits of H. pylori eradication should be carefully balanced against the risk of adverse effects especially in the elderly, persons with frailty, and intolerance to antibiotics.
Topics: Humans; Aged; Gastrointestinal Microbiome; Helicobacter pylori; Helicobacter Infections; Anti-Bacterial Agents; Gastritis
PubMed: 37917397
DOI: 10.1007/s15010-023-02115-7 -
Journal of Neurogastroenterology and... Jul 2020Gastroesophageal reflux disease (GERD) is a complex disorder with heterogeneous symptoms and a multifaceted pathogenetic basis, which prevent a simple diagnostic... (Review)
Review
Gastroesophageal reflux disease (GERD) is a complex disorder with heterogeneous symptoms and a multifaceted pathogenetic basis, which prevent a simple diagnostic algorithm or any categorical classification. Clinical history, questionnaires and response to proton pump inhibitor (PPI) therapy are insufficient tools to make a conclusive diagnosis of GERD and further investigations are frequently required. The Lyon Consensus goes beyond the previous classifications and defines endoscopic and functional parameters able to establish the presence of GERD. Evidences for reflux include high-grade erosive esophagitis, Barrett's esophagus, and peptic strictures at endoscopy as well as esophageal acid exposure time > 6% on pH-metry or combined pH-impedance monitoring. Even if a normal endoscopy does not exclude GERD, its combination with distal acid exposure time < 4% on off-PPI pH-impedance monitoring provides sufficient evidence refuting this diagnosis. Reflux-symptom association on pH-monitoring provides supportive evidence for reflux-triggered symptoms and may predict a better treatment outcome, when present. Also recommendations to perform pH-impedance "on" or "off" PPI are well depicted. When endoscopy and pH-metry or combined pH-impedance monitoring are inconclusive, adjunctive evidence from biopsy findings (eg, microscopic esophagitis), high-resolution manometry (ie, ineffective esophagogastric barrier and esophageal body hypomotility), and novel impedance metrics, such as mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index, can contribute to better identify patients with GERD. Definition of individual patient phenotype, based on the level of refluxate exposure, mechanism of reflux, efficacy of clearance, underlying anatomy of the esophagogastric junction, and clinical presentation, will lead to manage GERD patients with a tailored approach chosen among different types of therapy.
PubMed: 32606254
DOI: 10.5056/jnm20046 -
Scientific Reports Aug 2023Gastro-esophageal reflux disease (GERD) can cause erosive esophagitis (EE) and compromise the quality of life (QoL). We examined differences in symptom severity and QoL...
Gastro-esophageal reflux disease (GERD) can cause erosive esophagitis (EE) and compromise the quality of life (QoL). We examined differences in symptom severity and QoL according to EE severity grade. A follow-up study was conducted among GERD patients at the Nazareth Hospital in Israel. Patients underwent a baseline gastroscopy in 2014-2020 during which the EE grade was determined using the Los Angeles classification. Follow-up telephone interviews were conducted during 2019-2020 with a mean time interval of 18.9 months (SD = 14.9) after the baseline gastroscopy to assess GERD symptoms using the Reflux disease questionnaire (RDQ) and QoL using the GERD QoL questionnaire. The patients were interviewed in their native language (Arabic or Hebrew). Overall, 149 (66.4% males) patients were included; 50 had EE grades C/D and 99 had grades A/B. The mean age at baseline and follow-up was 44.6 years (SD = 15.1) and 46.2 years (SD = 14.9), respectively. Cronbach's alpha was 0.928 and 0.855 for the RDQ and QoL questionnaires, respectively. Patients with EE C/D grades had more severe symptoms than patients with EE A/B grades (P = 0.05), especially in regurgitation scores (P = 0.03). Females had more severe symptoms (overall) than males (adjusted OR = 2.34; 95% CI 1.12-4.90). Patients with the more severe esophagitis EE C/D group (adjusted OR = 1.98; 95% CI 0.93-4.24) and those who used PPIs treatment (adjusted OR = 2.19; 95% CI 0.95-5.01) reported more severe GERD symptoms. The number of schooling years was significantly associated with better QoL score (beta coefficient 1.33, P = 0.005) but not EE grade or GERD symptoms. Follow-up endoscopy conducted among 22 patients with EE grades C/D showed that 13 (59.1%) of these patients had normal endoscopic findings, 6 patients (27.3%) had a grade A EE, 1 patient (4.5%) had grade B, and 2 (9.1%) remained with grade C EE. The Arabic and Hebrew versions of the RDQ and QoL questionnaires were highly reliable. GERD symptoms severity was more profound among patients with more severe esophagitis. No significant association between EE grade and QoL; this negative result might be due to the improvement in esophagitis endoscopic findings among patients with C/D grade.
Topics: Female; Male; Humans; Esophagitis, Peptic; Prospective Studies; Quality of Life; Follow-Up Studies; Peptic Ulcer; Gastroesophageal Reflux
PubMed: 37634042
DOI: 10.1038/s41598-023-41332-w -
Pharmacology & Therapeutics Dec 2016Acid-related diseases (ARDs), such as peptic ulcers and gastroesophageal reflux disease, represent a major health-care concern. Some major milestones in our... (Review)
Review
Acid-related diseases (ARDs), such as peptic ulcers and gastroesophageal reflux disease, represent a major health-care concern. Some major milestones in our understanding of gastric acid secretion and ARD treatment reached during the last 50years include 1) discovery of histamine H-receptors and development of H-receptor antagonists, 2) identification of H,K-ATPase as the parietal cell proton pump and development of proton pump inhibitors (PPIs), and 3) identification of Helicobacter pylori (H. pylori) as the major cause of peptic ulcers and development of effective eradication regimens. Although PPI treatments have been effective and successful, there are limitations to their efficacy and usage, i.e. short half-life, insufficient acid suppression, slow onset of action, and large variation in efficacy among patients due to CYP2C19 metabolism. Potassium-competitive acid blockers (P-CABs) inhibit H,K-ATPase in a reversible and K-competitive manner, and exhibit almost complete inhibition of gastric acid secretion from the first dose. Many pharmaceutical companies have tried to develop P-CABs, but most of their clinical development has been discontinued due to safety concerns or a similar efficacy to PPIs. Revaprazan was developed in Korea and was the first P-CAB approved for sale. Vonoprazan, approved in 2014 in Japan, has a completely different chemical structure and higher pKa value compared to other P-CABs, and exhibits rapid onset of action and prolonged control of intragastric acidity. Vonoprazan is an effective treatment for ARDs that is especially effective in healing reflux esophagitis and for H. pylori eradication. P-CABs, such as vonoprazan, promise to further improve the management of ARDs.
Topics: Animals; Drug Design; Gastric Acid; Gastroesophageal Reflux; Gastrointestinal Agents; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Peptic Ulcer; Potassium; Proton Pump Inhibitors
PubMed: 27514776
DOI: 10.1016/j.pharmthera.2016.08.001 -
Therapeutic Advances in Gastroenterology 2023Since the discovery of () as the causative organism for gastric and duodenal ulcers four decades ago and subsequent recognition as class 1 gastric carcinogen, countless... (Review)
Review
Since the discovery of () as the causative organism for gastric and duodenal ulcers four decades ago and subsequent recognition as class 1 gastric carcinogen, countless numbers of studies have been conducted and papers published, on the efficacy of various management strategies to eradicate the infection. In adults, a global consensus by the experts in the field concluded that gastritis is an infectious disease and requires treatment irrespective of the presence or absence of symptoms due to the potential for serious complication like peptic ulcer disease and gastric neoplasia. However, although more than half the world's population harbors , these serious complications occur only in a small minority of the infected population, even less so in childhood. More importantly, there is accumulating evidence for beneficial role of against many chronic health conditions, from several epidemiological and laboratory studies. No doubt, eradication therapy is indicated in children with related peptic ulcer disease. Even though the pediatric guidelines from various learned societies recommend against a "test and treat" strategy, this is not always adhered to. With the accumulating evidence of the possible beneficial role of , it is time to pause and think, are we causing more harm than good by eradicating in every child who has this bug?
PubMed: 37361453
DOI: 10.1177/17562848231177610 -
Journal of Gastroenterology Jul 2017Reflux esophagitis damages the squamous epithelium that normally lines the esophagus, and promotes replacement of the damaged squamous lining by the intestinal... (Review)
Review
Reflux esophagitis damages the squamous epithelium that normally lines the esophagus, and promotes replacement of the damaged squamous lining by the intestinal metaplasia of Barrett's esophagus, the precursor of esophageal adenocarcinoma. Therefore, to prevent the development of Barrett's metaplasia and esophageal adenocarcinoma, the pathogenesis of reflux esophagitis must be understood. We have reported that reflux esophagitis, both in a rat model and in humans, develops as a cytokine-mediated inflammatory injury (i.e., cytokine sizzle), not as a caustic chemical injury (i.e., acid burn), as traditionally has been assumed. Moreover, reflux induces activation of hypoxia inducible factor (HIF)-2α, which enhances the transcriptional activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) causing increases in pro-inflammatory cytokines and in migration of T lymphocytes, an underlying molecular mechanism for this cytokine-mediated injury. In some individuals, reflux esophagitis heals with Barrett's metaplasia. A number of possibilities exist for the origin of the progenitor cells that give rise to this intestinal metaplasia including those of the esophagus, the proximal stomach, or the bone marrow. However, intestinal cells are not normally found in the esophagus, the stomach, or the bone marrow. Thus, the development of Barrett's intestinal metaplasia must involve some molecular reprogramming of key developmental transcription factors within the progenitor cell, a process termed transcommitment, which may be initiated by the noxious components of the gastric refluxate. This review will highlight recent studies on the pathogenesis of reflux esophagitis and on reflux-related molecular reprogramming of esophageal squamous epithelial cells in the pathogenesis of Barrett's metaplasia.
Topics: Animals; Barrett Esophagus; Basic Helix-Loop-Helix Transcription Factors; CDX2 Transcription Factor; Cell Transdifferentiation; Cellular Reprogramming; Cytokines; Epithelial Cells; Esophagitis, Peptic; Hedgehog Proteins; Hepatocyte Nuclear Factor 3-beta; Humans; NF-kappa B; Proto-Oncogene Proteins c-akt; SOX9 Transcription Factor; SOXB1 Transcription Factors; Signal Transduction; Stem Cells; Transcription Factors
PubMed: 28451845
DOI: 10.1007/s00535-017-1342-1 -
Digestive Diseases (Basel, Switzerland) 2022Dyspepsia is a very frequent condition, affecting up to 50% of general population. Primary care is the logical setting for starting a management. In treating dyspeptic... (Review)
Review
BACKGROUND
Dyspepsia is a very frequent condition, affecting up to 50% of general population. Primary care is the logical setting for starting a management. In treating dyspeptic patients, it is a crucial point to distinguish between functional problems, common diseases such as reflux esophagitis or peptic ulcer, and life-threatening diseases such as upper gastrointestinal (GI) cancer. In Europe, there are different approaches to this problem. We describe the management of dyspepsia, with a particular focus on relationship between dyspepsia and gastric cancer.
SUMMARY
Initial treatment of dyspepsia includes empirical treatment, noninvasive testing for Helicobacter pylori, and upper GI tract endoscopy. Treatment choice is based on different variables, including alarm signs, patient preference, and possibility to perform a gastroscopy. General practitioners are not allowed in all European nations to order a gastroscopy. This may have some reflection on quality of cure.
KEY MESSAGE
In European countries, there are heterogeneities in terms of gastric cancer incidence, mortality, and quality of cure. Awareness of them is a first step in identifying possible solutions.
Topics: Dyspepsia; Endoscopy, Gastrointestinal; Helicobacter Infections; Helicobacter pylori; Humans; Primary Health Care; Prospective Studies; Stomach Neoplasms
PubMed: 33971660
DOI: 10.1159/000517112 -
BMC Gastroenterology May 2023VISION is a randomised, phase 4, open-label, parallel-group, multicentre study conducted in 33 centres in Japan. The aim of this study was to assess the long-term safety... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomised clinical trial: 3-year interim analysis results of the VISION trial to evaluate the long-term safety of vonoprazan as maintenance treatment in patients with erosive oesophagitis.
BACKGROUND
VISION is a randomised, phase 4, open-label, parallel-group, multicentre study conducted in 33 centres in Japan. The aim of this study was to assess the long-term safety of vonoprazan for maintenance treatment of healed erosive oesophagitis versus lansoprazole.
METHODS
Patients with endoscopically diagnosed erosive oesophagitis were randomised 2:1 to once-daily vonoprazan 20 mg or lansoprazole 30 mg, for a 4- to 8-week healing phase. Patients with endoscopically confirmed healing entered a 260-week maintenance phase with a once-daily starting dose of vonoprazan 10 mg or lansoprazole 15 mg. Primary endpoint was change in gastric mucosal histopathology.
RESULTS
Of 208 patients (vonoprazan, n = 139; lansoprazole, n = 69) entering the healing phase, 202 entered the maintenance phase (vonoprazan, n = 135; lansoprazole, n = 67). At 3 years, 109 vonoprazan-treated and 58 lansoprazole-treated patients remained on treatment. Histopathological evaluation of gastric mucosa showed that hyperplasia of parietal, foveolar and G cells was more common with vonoprazan than lansoprazole at week 156 of the maintenance phase. There was no marked increase in the occurrence of parietal, foveolar and G cell hyperplasia among patients in the vonoprazan group from week 48 to week 156. Histopathological evaluation of the gastric mucosa also showed no neoplastic changes in either group. No new safety issues were identified.
CONCLUSIONS
In this interim analysis of VISION, no new safety concerns were identified in Japanese patients with healed erosive oesophagitis receiving vonoprazan or lansoprazole as maintenance treatment for 3 years. (CT.gov identifier: NCT02679508; JapicCTI-163153; Japan Registry of Clinical Trials: jRCTs031180040).
Topics: Humans; Proton Pump Inhibitors; Hyperplasia; Esophagitis; Lansoprazole; Peptic Ulcer; Treatment Outcome; 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Double-Blind Method
PubMed: 37127558
DOI: 10.1186/s12876-023-02772-w -
World Journal of Gastroenterology Jul 2022Proton pump inhibitors (PPIs), the most commonly used antisecretory medi-cations in the management of reflux illness, virtually eliminate elective surgery for ulcer... (Review)
Review
Proton pump inhibitors (PPIs), the most commonly used antisecretory medi-cations in the management of reflux illness, virtually eliminate elective surgery for ulcer disease, and relegate anti-reflux surgery to patients with gastroesophageal reflux disease (GERD) who are inadequately managed by medical therapy. However, PPI medications still leave some therapeutic demands of GERD unmet. Furthermore, up to 40%-55% of daily PPI users have chronic symptoms, due to PPI refractoriness. Potassium-competitive acid blockers (P-CABs) transcend many of the problems and limits of PPIs, delivering quick, powerful, and extended acid suppression and allowing for treatment of numerous unmet needs. Recently, it has become clear that compromised mucosal integrity plays a role in the etiology of GERD. As a result, esophageal mucosal protection has emerged as a novel and potential treatment approach. An increasing body of research demonstrates that when P-CABs are used as primary drugs or add-on drugs (to regular treatment), they provide a considerable extra benefit, particularly in alleviating symptoms that do not respond to PPI therapy.
Topics: Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Potassium; Proton Pump Inhibitors
PubMed: 36161043
DOI: 10.3748/wjg.v28.i28.3608 -
Diseases of the Esophagus : Official... Sep 2023This study aimed to investigate the significance of Hill classification to predict esophagitis, Barrett's esophagus, gastroesophageal reflux disease (GERD)...
This study aimed to investigate the significance of Hill classification to predict esophagitis, Barrett's esophagus, gastroesophageal reflux disease (GERD) symptomatology, and future prescriptions of proton pump inhibitors in clinical practice. A total of 922 patients (546 women and 376 men; mean age 54.3 [SD 18.4] years) who underwent gastroscopy between 2012 and 2015 were analyzed. Patient questionnaire regarding symptoms were compared with endoscopy findings. A medical chart review was done that focused on the prescription of PPIs, additional gastroscopies, and GERD surgery in a 3-year period before the index gastroscopy and in a 6-year period afterward. In patients naïve to PPI prescriptions (n = 466), Hill grade III was significantly associated with esophagitis (AOR 2.20; 95% CI 1.00-4.84) and > 2 PPI prescriptions 6 year after the index gastroscopy (AOR 1.95; 95% CI 1.01-3.75), whereas Hill grade IV was significantly associated with esophagitis (AOR 4.41; 95% CI 1.92-10.1), with Barrett's esophagus (AOR 12.7; 95% CI 1.45-112), with reported heartburn (AOR 2.28; 95% CI 1.10-4.74), and with >2 PPI prescriptions (AOR 2.16; 95% CI 1.02-4.55). In patients 'non-naïve' to PPI prescription (n = 556), only Hill grade IV was significantly associated with esophagitis, reported heartburn, and with >2 PPI prescriptions. The gastroscopic classification in Hill grades III and IV is important in clinical practice because they are associated with esophagitis, Barrett's esophagus, symptoms of GERD, and prescriptions of PPIs, whereas a differentiation between Hill grades I and II is not.
Topics: Male; Humans; Female; Middle Aged; Barrett Esophagus; Esophagitis, Peptic; Heartburn; Gastroesophageal Reflux; Proton Pump Inhibitors
PubMed: 36744860
DOI: 10.1093/dote/doad004