Helicobacter pylori in peptic ulcer disease: pathogenesis, gastric microbiome, and innovative therapies

The frequency of Helicobacter pylori (HP) infection in 208 patients with upper gastrointestinal tract symptoms from the Southern Province of Saudi Arabia was studied prospectively. The occurrence of HP was documented histologically and using a rapid urease test in antral endoscopic biopsies. Our results showed that 82.2% of the 208 patients included were positive for HP with a male:female ratio of approximately 1:1 (88:83). The age range was 14 to 80 years and the median age was 38.2 years. The frequencies of HP infection among Saudi and non-Saudi patients were 86% and 71%, respectively. Frequencies of HP infection were 88%, 77.5%, and 93% during the second, third, and fourth decades of life. Among the 140 patients with histologically proven antral gastritis, 128 cases (91%) were positive for HP whereas 29 cases (17%) of the 171 patients positive for HP did not show histologic evidence of antral gastritis. Our data showed that HP was present in 92.5% of patients with endoscopic diagnosis of duodenal ulceration, 81% of patients with duodenitis, 80% of patients with both duodenitis and gastritis, 69% of patients with gastric antral erythema, and 81% of patients with non-ulcer dyspepsia (normal upper gastrointestinal endoscopy). Histologically proven antral gastritis was seen in 80% of patients with endoscopic diagnosis of duodenal ulceration, 76% of patients with antral erythema, 70% of patients with both duodenitis and gastritis, 33% of patients with duodenitis only, and 66% of patients with non-ulcer dyspepsia. Among the 208 patients included in the study, gastric ulcerationw as only seen in two cases, both positive for HP.

Effects of Helicobacter pylori and Nonsteroidal Anti-Inflammatory Drugs on Peptic Ulcer Disease: A Systematic Review

The issues of how best to diagnose the presence of Helicobacter pylori and how best to eliminate this organism must follow from the larger question: In whom is elimination of H. pylori beneficial?

Alimentary Pharmacology & TherapeuticsVolume 9, Issue 1 p. 85-86 Free Access Letters to the Editors W. A. de Boer, W. A. de Boer Saint Joseph Hospital Department of Internal Medicine Veldhoven, The NetherlandsSearch for more papers by this authorJ. G. Penston, J. G. Penston Medical Consultant to Glaxo Pharmaceuticals UK Ltd Dundee, UKSearch for more papers by this author W. A. de Boer, W. A. de Boer Saint Joseph Hospital Department of Internal Medicine Veldhoven, The NetherlandsSearch for more papers by this authorJ. G. Penston, J. G. Penston Medical Consultant to Glaxo Pharmaceuticals UK Ltd Dundee, UKSearch for more papers by this author First published: February 1995 https://doi.org/10.1111/j.1365-2036.1995.tb00357.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Penston J G, Review article: Helicobacter pylori eradication—understandable caution but no excuse for inertia. Aliment Pharmacol Ther 1994; 8: 369– 89. 2 National Institute of Health Consensus Conference. Helicobacter pylori in peptic ulcer disease. JAMA 1994; 272: 65– 9. 3 Wilhelmsen I, Berstad A. Quality of life and relapse of duodenal ulcer before and after eradication of Helicobacter pylori. Scand J Gastroenterol 1994; 29: 874– 9. 4 Labenz J, Borsch G. Highly significant change of the clinical course of relapsing and complicated peptic ulcer disease after cure of Helicobacter pylori infection. Am J Gastroenterol 1994; 89: 1785– 8. 5 Borody T J, Andrews P, Manusco N, et al. Helicobacter pylori reinfection rate in patients with cured duodenal ulcer. Am J Gastroenterol 1994; 89: 529– 32. 6 de Boer W A, Driessen W M M, Potters H V P J, Tytgat G N J. Randomized study comparing 1 with 2 weeks of quadruple therapy for eradicating Helicobacter pylori. Am J Gastroenterol 1994; 89 (November). (in press). 7 de Boer W A, Driessen W M M, Jansz A R, Tytgat G N J. Concomitant acid suppression increases the efficacy of traditional anti-Helicobacter pylori triple therapy. Results of a randomised prospective study of triple therapy with or without omeprazole. Presented at the scientific meeting of the Dutch society of Gastroenterology, Veldhoven, October 1994 (Abstract). REFERENCES 1 Penston J G. Review article: Helicobacter pylori eradication—understandable caution but no excuse for inertia. Aliment Pharmacol Ther 1994; 8: 369– 89. 2 National Institute of Health Consensus Conference. Helicobacter pylori in peptic ulcer disease. JAMA 1994; 272: 65– 9. Volume9, Issue1February 1995Pages 85-86 ReferencesRelatedInformation

The National Institutes of Health Consensus Development Conference on<i>Helicobacter pylori</i>in Peptic Ulcer Disease brought together specialists in gastroenterology, surgery, infectious diseases, epidemiology, and pathology, as well as the public to address the following questions: (1) What is the causal relationship of<i>H pylori</i>to upper gastrointestinal disease? (2) How does one diagnose and eradicate<i>H pylori</i>infection? (3) Does eradication of<i>H pylori</i>infection benefit the patient with peptic ulcer disease? (4) What is the relationship between<i>H pylori</i>infection and gastric malignancy? (5) Which<i>H pylori</i>—infected patients should be treated? (6) What are the most important questions that must be addressed by future research in<i>H pylori</i>infections? Following 1½ days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the consensus panel concluded that (1) ulcer patients with<i>H pylori</i>infection require treatment with antimicrobial agents in addition to antisecretory drugs whether on first presentation with the illness or on recurrence; (2) the value of treating of nonulcerative dyspepsia patients with<i>H pylori</i>infection remains to be determined; and (3) the interesting relationship between<i>H pylori</i>infection and gastric cancers requires further exploration. (<i>JAMA</i>. 1994;272:65-69)

Back ground:Epigastric pain pain in the mid-upper abdomen. The differential diagnosis of epigastric pain is broad. Pain in this area can be due to gastroenterological, pancreaticobiliary and other causes, including non-gastroenterological disease. The prevalence of gastric pathology has been studied in detail and incidence of Helicobacter Pylori in peptic ulcer disease has been analysed.Methods:All the patients attending the OPD with epigastric pain has been examined and those cases with pathology affecting organs other than stomach have been excluded. The remaining patients has been subjected to routine endoscopic biopsy and screening for H.Pylori (by Rapid Urease Test).Results:Prevalence of disease with epigastric pain with reference to gastric pathology in this community is 83.3%.Incidence of helicobacter pylori among the patients with acid peptic ulcer disease symptoms was up to 74% which correlate with the world wide prevalence.Conclusion:Patients attending hospital with epigastric pain are mostly due to gastric pathology-acid peptic ulcer disease with high incidence of Helicobacter pylori. Hence patients attending hospital with epigastric pain, after excluding the causes of pain due to organs other than stomach should be subjected to routine upper gastro intestinal endoscopy, endoscopic biopsy and should be screened for Helicobacter pylori. Which highly prevent the patients more susceptible for carcinoma stomach. More over promotion of health education and awareness of the disease makes the patients present to hospital at earlier stage and prevents devastating complications. INTRODUCTION EPIGASTRIC PAIN PAIN IN THE MID-UPPER ABDOMEN The differential diagnosis of epigastric pain is broad. Pain in this area can be due to gastroenterological, pancreaticobiliary and other causes, including nongastroenterological disease .Gastrointestinal causes of epigastric pain include: Ulcers (stomach or duodenum), Non-ulcer dyspepsia/indigestion, Irritable bowel syndrome, Gastro oesophageal reflux disease (GERD), Stomach cancer, and abdominal wall hernias. Pancreaticobiliary causes of epigastric pain include: Acute pancreatitis, Chronic pancreatitis , Cholecystitis ,Gallbladder dyskinesia, Sphincter of Oddi dysfunction, Pancreatic cancer,Pancreatic cysts and pseudocysts,Cholangitis,Bile duct stones, Pancreas divisum. Non-gastroenterological causes of epigastric pain include: Atypical manifestation of coronary heart disease/angina, Myocardial infarction, especially that of the posterior wall of the heart other causes are also possible. The most common gastroenterological cause is “Peptic ulcer disease (PUD)” Peptic ulcer disease (PUD) is defined as an erosion in the lining of the stomach or duodenum.” peptic” alludes to pepsin, a proteolytic enzyme that catalyzes the hydrolysis of proteins. About 4-10% develops PUD at some point.PUD incidence increases with age, with PUD most common in those older than 40yrs. The major forms of peptic ulcer are duodenal ulcer (DU) and gastric ulcer (GU).There exists incomplete knowledge regarding the cause of peptic ulcer disease. Available information, however, supports a central role for H. pylori and a necessary role for acid and pepsin. Despite the focus on the role of infection with H. pylori, an understanding of basic gastric physiology remains central to a consideration of ulcer pathogenesis. Although PUD has a variety of causes, including stress, NSAID use, smoking...it is most frequently associated with HELICOBACTER PYLORI this accounts for 90% of diagnosed cases. AIM OF THE STUDY To identify the causes of epigastric pain of gastric origin in this community. Prevalance Of Disease With Epigastric Pain With Reference To Gastric Pathology 2 of 6 To correlate mainly the peptic ulcer disease with the presence of H.Pylori incidence. MATERIALS AND METHODS To examine all the patients attending the OPD with epigastric pain and to exclude those cases with pathology affecting organs other than stomach by USG (ultrasound abdomen), biochemical analysis, ECG, Chest X ray as per the case. To subject the remaining patients to routine endoscopic biopsy and screening for H.Pylori (by Rapid Urease Test). INCLUSION AND EXCLUSION CRITERIA’S

The National Institutes of Health Consensus Development Conference on Helicobacter pylori in Peptic Ulcer Disease brought together specialists in gastroenterology, surgery, infectious diseases, epidemiology, and pathology, as well as the public to address the following questions: (1) What is the causal relationship of H pylori to upper gastrointestinal disease? (2) How does one diagnose and eradicate H pylori infection? (3) Does eradication of H pylori infection benefit the patient with peptic ulcer disease? (4) What is the relationship between H pylori infection and gastric malignancy? (5) Which H pylori —infected patients should be treated? (6) What are the most important questions that must be addressed by future research in H pylori infections? Following 1½ days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the consensus panel concluded that (1) ulcer patients with H pylori infection require treatment with antimicrobial agents in addition to antisecretory drugs whether on first presentation with the illness or on recurrence; (2) the value of treating of nonulcerative dyspepsia patients with H pylori infection remains to be determined; and (3) the interesting relationship between H pylori infection and gastric cancers requires further exploration. ( JAMA . 1994;272:65-69)

Background and Aims: The aim of this prospective, randomized trial was to compare bismuth-based quadruple therapy with levofloxacin-based triple therapy for the second-line eradication of Helicobacter pylori in peptic ulcer disease. Materials and Methods: From March 2014 to August 2015, 18 Helicobacter pylori-positive patients with peptic ulcer disease were consecutively randomized into two groups after 14 days of clarithromycin-based classic triple eradication. Group 1 (n=10) was given bismuth-based quadruple therapy and group 2 (n=8) was given levofloxacin-based triple therapy. In both groups, lansoprazole (1x1) was completed in 12 weeks. After a 15-day washout period, a urea breath test and Helicobacter pylori stool antigen test were performed to monitor eradication. Results: Sixty percent of the patients in group 1 were female, mean age was 45.7±8.8 (range: 36- 66) years, and in group 2, the mean age was 45.1±7.9 years (range: 29-54). The urea breath test and Helicobacter pylori stool antigen test were negative in 9 patients in group 1 (eradication rate: 90%) and 3 patients in group 2 (eradication rate: 38%). There was a significant difference in the eradication rate between the two groups in favor of bismuth-based quadruple therapy (p < 0.005). Conclusion: We conclude that bismuth-based quadruple therapy is superior to levofloxacin-based triple therapy for the second-line eradication of Helicobacter pylori in peptic ulcer disease. Although the number of patients was low in our study, this result might have been due to levofloxacin resistance. We propose that regional differences may have a role in second- line therapy, and more comprehensive studies including more patients are needed to address this issue.

INTRODUCTION: It is known that Helicobacter pylori (HP) plays an important role in gastritis and peptic ulcer disease. In addition, the International Agency for Research on Cancer (IARC) categorized HP infection as a type I carcinogen and it is considered as the primary cause of gastric cancer. HP eradication reduces relapse in peptic ulcer and decreases gastric cancer risk. The incidence of gastrointestinal (GI) complications in renal transplant recipients (RTRs) is relatively high and complications may be severe and may lead to graft loss and even patient death. The most frequently found gastrointestinal disease in transplant recipients is the peptic ulcer, a frequent cause of mortality, accounting for 4% of deaths after transplantation. In transplant patients, immunosuppression such as cyclosporine A (CyA), steroids (STs) and Mycophenolate mofetil (MMF) contributes much more to cancer risk because it interrupts normal cancer surveillance mechanism. Incidence of malignant tumors in transplant recipients is 3 to 5 times higher than in the general population. Therefore, the accurate assessment of HP infection status in renal transplant recipients is important. There is currently no information on the prevalence of HP in renal transplant recipients in Pakistan. So, this study will help fill this gap in knowledge on the prevalence of HP in our population. OBJECTIVE To determine the frequency of Helicobacter pylori (HP) infection in gastric biopsies in renal transplant recipients with upper gastrointestinal symptoms. STUDY DESIGN: Descriptive, cross-sectional study. DURATION OF STUDY: Six months (December 2019-May 2020). SUBJECTS AND METHODS: All renal transplant patients of age range 10-65 years (children and adults) of any gender who had any one or more of the upper gastrointestinal symptoms such as epigastric pain, burning, nausea and vomiting, post prandial fullness and early satiety and in whom gastro-intestinal endoscopy and biopsies were performed, were included in the study. Data was collected from request forms and clinical charts. Age, sex and presence/absence of HP were recorded on a structured proforma. RESULTS: A total of 315 renal transplant recipients and non-renal transplant recipients underwent upper gastro-intestinal endoscopy in the gastroenterology department of SIUT, Karachi, during the study period. Of these, 106 consecutive biopsies of renal transplant recipients who had gastrointestinal symptoms were eligible for inclusion in the study. Out of which, 86 (81.1%) were male and 20 (18.9%) were female with a male to female ratio of 4.3:1. The mean age of all patients was 34.5±10.15 years (range: 12-65 years); the median age was 33.67 years. Majority of patients, 70 out of 106 (66.1%), were in age group ranging from 20-40 years. HP infection was positive in 11 (10.4%) biopsies of renal transplant recipients. Chronic active (diffuse) inflammation was observed in 9 (81.81%), chronic active (focal) gastritis in 1 (9.09%) and follicular gastritis with activity in 1 (9.09 %) biopsies with HP infection. Intestinal metaplasia (IM) was found in two (18.2%) biopsies. All patients in positive group were males (100%). The most frequent gastrointestinal complaints noticed in HP positive patients were weight loss in nine (81.81%) patients followed by epigastric pain in three (27.27%) patients. No correlation was found between gender (p=0.168) and age (p=0.36) and occurrence of HP infection. The other 95 (89.6%) gastric biopsies of renal transplant recipients were negative for HP infection. The histological findings included chronic nonspecific gastritis in 83 (89.2%), chronic active (diffuse) gastritis in 5 (5.4%), chronic active (focal) gastritis in 3 (3.2) and follicular gastritis with activity in 2 (2.2%). Goblet cell metaplasia was found in 5 (5.3%) HP negative biopsies. CONCLUSION: In conclusion, the frequency of HP infection is 10.4% in our renal transplant recipients which is quiet low compared to non-transplant patients. Further, large scale studies are needed to determine the true prevalence of this common pathogen in our transplant population.

The past decade has witnessed a global rise in the prevalence of peptic ulcer disease which is unrelated to non-steroidal anti-inflammatory drugs (NSAIDs) or Helicobacter pylori infection. Although initially recognized in the West, this disease is being increasingly recognized in the Asian population. The higher risk of bleeding and ulcer recurrence in this subgroup of patients highlights the clinical importance of analyzing the changing trends of peptic ulcer disease in developing countries. To assess the proportion of non-NSAID, non-H. pylori peptic ulcer disease in an Indian cohort of patients with peptic ulcer disease managed at a tertiary care center; and to compare the gastric and duodenal ulcer subgroups in these patients. Patients diagnosed with peptic ulcer disease were screened for a history of NSAID use and those with a negative history were tested for H. pylori using a combination of rapid urease test (RUT) and (14)C-urea breath test (UBT). Only those cases which tested negative for both the tests were considered 'H. pylori-negative'. Serum gastrin was measured in all patients included in the study. Seventy-four gastric ulcer (GU) and 54 duodenal ulcer (DU) patients with no history of NSAID use were enrolled. Of these, 36 GU (45.9%) and 16 DU (29.6%) patients were H. pylori-negative. The proportion of non-NSAID non-H. pylori gastric ulcers was significantly higher than duodenal ulcers (p < 0.05). However, patients who tested negative for H. pylori did not differ significantly from those who tested positive with regard to age, gender, serum gastrin level, and presence of risk factors, like smoking and alcoholism. The current study indicates existence of high proportion of non-NSAID, non-H. pylori peptic ulcer disease in Indian patients.

Helicobacter pylori is an important risk factor of gastric cancer (GC). Although many H. pylori virulence factors have been reported, the pathogenic mechanism by which H. pylori infection causes GC remains unclear. The aims of this study were to identify GC-related antigens from H. pylori and characterize their roles in the development of GC. As GC and duodenal ulcer (DU) are considered clinically divergent, we compared two-dimensional immunoblots of an acid-glycine extract of H. pylori probed with serum samples from 15 patients with GC and 15 with DU to find GC-related antigens, which were subsequently identified by mass spectrometry. Many protein spots were recognized by more than one serum, and 24 of these were better recognized by GC sera. The proteins showing higher frequency of recognition in GC group are threonine synthase, rod shape-determining protein, S-adenosylmethionine synthetase, peptide chain release factor 1, DNA-directed RNA polymerase alpha subunit, co-chaperonin GroES (monomeric and dimeric forms), response regulator OmpR, and membrane fusion protein. Of these proteins, GroES was identified as a dominant GC-related antigen with a much higher seropositivity of GC samples (64.2%, n = 95) compared with 30.9% for gastritis (n = 94) and 35.5% for DU (n = 124). GroES seropositivity was more commonly associated with antral GC than with non-antral GC (odds ratio = 2.7; 95% confidence interval, 1.1-6.7). In peripheral blood mononuclear cells, GroES stimulated production of interleukin (IL)-8, IL-6, granulocyte macrophage colony-stimulating factor, IL-1beta, tumor necrosis factor-alpha, cyclooxygenase-2, and prostaglandin E(2). Moreover when incubated with gastric epithelial cells, GroES induced expression of IL-8, cell proliferation, and up-regulation of c-jun, c-fos, and cyclin D1 but caused down-regulation of p27(Kip1). We conclude that GroES of H. pylori is a novel GC-associated virulence factor and may contribute to gastric carcinogenesis via induction of inflammation and promotion of cell proliferation.

Introduction Helicobacter pylori is a Gram-negative bacterium, which infects over 50% of the population worldwide. However, only a subset of these infections result in gastrointestinal diseases, such as peptic ulceration (10%) and gastric cancer (2%). Several epidemiological studies have revealed that people who carry H. pylori are at a decreased risk of developing IBD. However, a mechanistic understanding of the association between H. pylori infection and IBD is still unknown. Unlike any other microbial species, once H. pylori colonises its gastric niche, it is able to dominate the gastric microbiome, representing 90%–95% of the total microbial population. Therefore, we hypothesised that the presence of H. pylori in the upper gastrointestinal (GI) tract prevents the colonisation of the lower GI tract with microbial species associated with the pathogenesis of IBD. Method To test this, we collected stool samples from IBD patients (comprising Ulcerative Colitis and Crohn’s disease patients) and determined their H. pylori status using a stool antigen test. We then characterised the intestinal microbiota of H. pylori positive (n=9) and negative IBD patients (n=18), by amplifying the V4 hyper-variable region of the 16S rRNA gene from faecal DNA. To determine the predominant phyla, these products were sequenced using the Illumina MiSeq and data analysis was performed using the QIIME pipeline and GreenGenes database. Results Interestingly, bacterial community structure revealed that there is a strong trend towards a decrease of Proteobacteria and an increase of Bacteroidetes in H. pylori positive IBD patients. Of note, IBD is generally characterised by an increase in Proteobacteria and a decrease in Bacteroidetes. Furthermore, using PICRUSt to investigate the functional composition of the metagenomes, we found that the H. pylori positive IBD patients displayed significant functional differences, including decreased bacterial motility and chemotaxis (p= Conclusion Our preliminary data suggests that the presence of H. pylori infection may promote a less pathogenic intestinal microbiome in patients with established IBD. This data provides the rationale to extend our studies with increased patient numbers and healthy controls to determine the mechanistic basis for the negative association of H. pylori infection and IBD. Disclosure of Interest None Declared

Helicobacter pylori (HP) can induce epithelial cells and intestinal metaplasia with genetic damage that makes them highly susceptible to the development of gastric cancer (GC). Between 2005 and 2010, 356 patients with gastric cancer who received curative surgery were enrolled. Analysis of HP, Epstein-Barr virus (EBV) infection, PIK3CA amplification, and mutation analysis of 68 mutations in eight genes using a mass spectrometric single-nucleotide polymorphism genotyping technology was conducted. The clinicopathological characteristics of patients with or without HP infection were compared. Among the 356 patients, 185 (52.0%) had HP infection. For intestinal-type GC, patients with HP infection were more likely to be younger and had fewer PI3K/AKT pathway genetic mutations than those without HP infection. For diffuse-type GC, patients with HP infection were characterized by less male predominance, less lymphoid stroma, fewer microsatellite instability-high tumors, and fewer PI3K/AKT pathway genetic mutations than those without HP infection. Patients with HP infection had less tumor recurrence and a better 5-year overall survival (87.7% vs. 73.9%, p = .012) and disease-free survival (64.1% vs. 51.3%, p = .013) than those without HP infection, especially for intestinal-type GC. For EBV-negative GC, patients with HP infection had fewer PI3K/AKT pathway mutations and a better 5-year overall survival and disease-free survival than those without HP infection. Multivariate analysis demonstrated that HP infection was an independent prognostic factor regarding overall survival and disease-free survival. Patients with GC with HP infection were associated with fewer PI3K/AKT pathway genetic mutations and better survival than those without HP infection, especially for EBV-negative and intestinal-type GC. Patients with gastric cancer with Helicobacter pylori (HP) infection had fewer PI3K/AKT pathway genetic mutations, less tumor recurrence, and better survival than those without HP infection, especially for Epstein-Barr virus (EBV)-negative and intestinal-type gastric cancer. HP infection is an independent prognostic factor regarding overall survival and disease-free survival. Future in vivo and in vitro studies of the correlation among HP infection, PI3K/AKT pathway, and EBV infection in gastric cancer are required.

AGA Institute Quality Measure Development for the Management of Gastric Intestinal Metaplasia With Helicobacter pylori

Epstein-Barr virus DNA load and its association with Helicobacter pylori infection in gastroduodenal diseases