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Background: Helicobacter pylori (H. pylori) infection is closely associated with gastrointestinal diseases. Our preliminary studies have indicated that H. pylori infection had a significant impact on the mucosal microbiome structure in patients with gastric ulcer (GU) or duodenal ulcer (DU)., Aim: To investigate the contributions of H . pylori infection and the mucosal microbiome to the pathogenesis and progression of ulcerative diseases., Methods: Patients with H . pylori infection and either GU or DU, and healthy individuals without H . pylori infection were included. Gastric or duodenal mucosal samples was obtained and subjected to metagenomic sequencing. The compositions of the microbial communities and their metabolic functions in the mucosal tissues were analyzed., Results: Compared with that in the healthy individuals, the gastric mucosal microbiota in the H . pylori -positive patients with GU was dominated by H . pylori , with significantly reduced biodiversity. The intergroup differential functions, which were enriched in the H . pylori -positive GU patients, were all derived from H . pylori , particularly those concerning transfer RNA queuosine-modification and the synthesis of demethylmenaquinones or menaquinones. A significant enrichment of the uibE gene was detected in the synthesis pathway. There was no significant difference in microbial diversity between the H. pylori -positive DU patients and healthy controls., Conclusion: H . pylori infection significantly alters the gastric microbiota structure, diversity, and biological functions, which may be important contributing factors for GU., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Helicobacter pylori is involved in the etiology and severity of several gastroduodenal diseases; however, plasticity of the H. pylori genome makes complete genome assembly difficult. We report here the full genomes of H. pylori strains CHC155 and VN1291 isolated from a non-cardia gastric cancer patient and a duodenal ulcer patient, respectively, and their virulence demonstrated by in vitro infection. Whole-genome sequences were obtained by combining long- and short-reads with a hybrid-assembly approach. Both CHC155 and VN1291 genome possessed four kinds of genomic island: a cag pathogenicity island (cagPAI), two type 4 secretion system islands within an integrative and conjugative element (tfs ICE), and prophage. CHC155 and VN1291 carried East Asian-type cagA and vacA s1m1, and outer membrane protein genes, including two copies of oipA. Corresponded to genetic determinants of antibiotic resistance, chromosomal mutations were identified in CHC155 (rdxA, gyrA, and 23S rRNA) and VN1291 (rdxA, 23S rRNA, and pbp1A). In vitro infection of AGS cells by both strains induced the cell scattering phenotype, tyrosine phosphorylation of CagA, and promoted high levels of IL8 secretion, indicating fully intact phenotypes of the cagPAI. Virulence genes in CHC155 and VN1291 genomes are crucial for H. pylori pathogenesis and are risk factors in the development of gastric cancer and duodenal ulcer. Our in vitro studies indicate that the strains CHC155 and VN1291 carry the pathogenic potential., (© 2023. The Author(s).)

Duodenal ulcer seriously affects the quality of life and life safety of children, but the pathogenesis of children with duodenal ulcer is still unclear. As an important second messenger in the body, Ca 2+ participates in the physiological and pathological processes of various diseases. Therefore, transient receptor potential vanilloid type 4 (TRPV4) as one of the channels that mediate Ca 2+ has attracted widespread attention in recent years. Here, we found that TRPV4 is highly expressed in children with duodenal ulcer and has good diagnostic value through specimens of children with duodenal ulcer, and animal experiments have proved that TRPV4 is also highly expressed in duodenal ulcer mice. In addition, TRPV4 can enhance intestinal permeability, thereby promoting further infiltration of inflammatory factors. In summary, these results indicate that TRPV4 is involved in the occurrence and development of duodenal ulcer. Therefore, this study provides the diagnostic and therapeutic value of TRPV4 in children with duodenal ulcer., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Chuanying Li et al.)

Genome-wide association studies (GWASs) can reveal genetic variations associated with a phenotype in the absence of any hypothesis of candidate genes. The problem of false-positive sites linked with the responsible site might be bypassed in bacteria with a high homologous recombination rate, such as Helicobacter pylori , which causes gastric cancer. We conducted a small-sample GWAS (125 gastric cancer cases and 115 controls) followed by prediction of gastric cancer and control (duodenal ulcer) H. pylori strains. We identified 11 single nucleotide polymorphisms (eight amino acid changes) and three DNA motifs that, combined, allowed effective disease discrimination. They were often informative of the underlying molecular mechanisms, such as electric charge alteration at the ligand-binding pocket, alteration in subunit interaction, and mode-switching of DNA methylation. We also identified three novel virulence factors/oncoprotein candidates. These results provide both defined targets for further informatic and experimental analyses to gain insights into gastric cancer pathogenesis and a basis for identifying a set of biomarkers for distinguishing these H. pylori -related diseases.

The prevalence of peptic ulcer diseases has decreased over the past decades. The contribution of Helicobacter pylori to these changes has not been clearly delineated. Two cohorts of patients receiving esophagogastroduodenoscopy examination together with urease test were enrolled, 1 from year 2001 (n = 1030), the other from year 2019 (n = 600). The prevalence changes of peptic ulcer diseases as well as the associated clinical factors were analyzed. An independent cohort of gastric biopsy samples (n = 151) positive for H. pylori were retrieved for ureC gene genotype analysis. Comparison between the patients recruited from 2001 and 2019 revealed significant decrease in H. pylori infection (P < 0.001), duodenal ulcer prevalence (P < 0.001) and gastric ulcer prevalence (P < 0.001). Multivariate analysis showed that the decreases of these factors were independent (adjusted P < 0.001 for all). Intriguingly, in H. pylori positive patients, the prevalence of duodenal ulcer still decreased with year (P < 0.001), which was not found in gastric ulcer (P = 0.345). Genetic analysis of H. pylori urease gene showed that MboI-restriction fragment length polymorphism-defined genotype 3 UreC was significantly more prevalent in gastric ulcer patients than in others (P = 0.022). Independent decreases of H. pylori infection, gastric ulcer and duodenal ulcer over decades were found. In H. pylori positive patients, duodenal ulcer prevalence decreased overtime while gastric ulcer prevalence remained unchanged. Gastric ulcer/cancer had a higher prevalence of MboI-defined genotype 3 UreC gene., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: While duodenal ulcer (DU) and gastric cancer (GC) are both H. pylori infection-related diseases, individuals with DU are known to have lower risk for GC. Many epidemiological studies have identified the PSCA rs2294008 T-allele as a risk factor of GC, while others have found an association between the rs2294008 C-allele and risk of DU and gastric ulcer (GU). Following these initial reports, however, few studies have since validated these associations. Here, we aimed to validate the association between variations in PSCA and the risk of DU/GU and evaluate its interaction with environmental factors in a Japanese population., Methods: Six PSCA SNPs were genotyped in 584 DU cases, 925 GU cases, and 8,105 controls from the Japan Multi-Institutional Collaborative Cohort (J-MICC). Unconditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the SNPs and risk of DU/GU., Results: PSCA rs2294008 C-allele was associated with per allele OR of 1.34 (95% CI, 1.18-1.51; P = 2.28 × 10 -6 ) for the risk of DU. This association was independent of age, sex, study site, smoking habit, drinking habit, and H. pylori status. On the other hand, we did not observe an association between the risk of GU and PSCA SNPs., Conclusions: Our study confirms an association between the PSCA rs2294008 C-allele and the risk of DU in a Japanese population.

Helicobacter pylori (H. pylori) is a Gram-negative, helically shaped flagellated bacterium. Major diseases associated with H. pylori infection include peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. The incidence of H. pylori in the anatomotopographic regions of the stomach, such as antrum, corpus, fundus, and incisura angularis, has been investigated. Do the rates of H. pylori in the settlements change over time according to the age ranges of the hosts? Does this change affect the diseases caused by or related to H. pylori? It is estimated that the outcomes, which have been obtained, may provide a new perspective in terms of understanding the etiopathogenesis of H. pylori-induced diseases. A comprehensive literature search of PubMed/MEDLINE databases had been conducted using a combination of terms, "Helicobacter pylori," "Sydney System," "stomach," "pyloric antrum," "gastric corpus," "stomach cancer," and "Helicobacter pylori and age." There are very few articles examining the relationship between the topographic locations of H. pylori and host age range in the English language literature. Therefore, it is also purposed to emphasize the outcomes of our current research about the mentioned topic. In our opinion, similar studies should reveal the settlement and age range in the different geographic locations and societies as in our study. We believe that these findings will contribute to the efforts for understanding overtly of H. pylori-induced disease of the stomach., Competing Interests: None

Helicobacter pylori chronically infects the stomach of approximately half of the world's population. Manifestation of clinical diseases associated with H. pylori infection, including cancer, is driven by strain properties and host responses; and as chronic infection persists, both are subject to change. Previous studies have documented frequent and extensive within-host bacterial genetic variation. To define how within-host diversity contributes to phenotypes related to H. pylori pathogenesis, this project leverages a collection of 39 clinical isolates acquired prospectively from a single subject at two time points and from multiple gastric sites. During the six years separating collection of these isolates, this individual, initially harboring a duodenal ulcer, progressed to gastric atrophy and concomitant loss of acid secretion. Whole genome sequence analysis identified 1,767 unique single nucleotide polymorphisms (SNPs) across isolates and a nucleotide substitution rate of 1.3x10-4 substitutions/site/year. Gene ontology analysis identified cell envelope genes among the genes with excess accumulation of nonsynonymous SNPs (nSNPs). A maximum likelihood tree based on genetic similarity clusters isolates from each time point separately. Within time points, there is segregation of subgroups with phenotypic differences in bacterial morphology, ability to induce inflammatory cytokines, and mouse colonization. Higher inflammatory cytokine induction in recent isolates maps to shared polymorphisms in the Cag PAI protein, CagY, while rod morphology in a subgroup of recent isolates mapped to eight mutations in three distinct helical cell shape determining (csd) genes. The presence of subgroups with unique genetic and phenotypic properties suggest complex selective forces and multiple niches within the stomach during chronic infection., Competing Interests: The authors have declared that no competing interests exist.

The objective of the present study was to establish the most suitable culture medium for the isolation of H. pylori from environmental and clinical samples. Ten different culture media were compared and evaluated. Four of them had been previously described and were modified in this study. The rest of the media were designed de novo. Three different matrices, tap water, wastewater, and feces, were inoculated with serial dilutions of H. pylori NCTC 11637 strain at a final concentration of 10 4 and 10 3  CFU/ml and the recovery rates were calculated. From inoculated tap water and wastewater samples, H. pylori colonies were recovered from four out of the analyzed culture media. When fecal samples were analyzed, the isolation of the pathogen under study was only possible from two culture media. Different optimal media were observed for each type of sample, even for wastewater and stool samples. Nevertheless, our results indicated that the combination of Dent Agar with polymyxin B sulfate did not inhibit the growth of H. pylori and was highly selective for its recovery, regardless of the sample origin. Thus, we propose the use of this medium as a diagnostic tool for the isolation of H. pylori from environmental and clinical samples, as well as for epidemiological studies.

Colonization of the human gastric mucosa by H. pylori may cause peptic and duodenal ulcers (DUs), gastric lymphomas, and gastric cancers. The cagL gene is a component of cag T4SS and is involved in cagA translocation into host. An association between the risk of gastric cancer and the type of HLA class II (DR and/or DQ) was suggested in different populations. The aim of this study was to investigate, the clinical association of the cagL gene with host HLA alleles in H. pylori strains that were isolated from patients with gastric cancer, DU, and non-ulcer dyspepsia (NUD) and to determine the HLA allele that confers susceptibility or resistance for the risk of gastric cancer and DU development in Turkish patients. A total of 94 patients (44 gastric cancer and 50 DU patients; 58 male, 36 female; mean age, 49.6 years), and 86 individuals (50 NUD patients and 36 persons with normal gastrointestinal system [NGIS]; 30 male, 56 female; mean age, 47.3 years) were included as the patient and the control groups, respectively. CagA and cagL were determined by PCR method. DNA from peripheral blood samples was obtained by EZ-DNA extraction kit. For HLA SSO typing, LIFECODES SSO Typing kits (HLA-A, HLA-B HLA-C, HLA-DRB1 and HLA-DQA1/B1 kits) were used. The CagL/CagA positivity distribution in the groups were as follows: 42 (95.4%) gastric cancer, 46 (92%) DU and, 34 (68%) NUD and no NGIS cases. The HLA-DQA1*01 (OR: 3.82) allele was significantly different, suggesting that these individuals with H. pylori strains harbouring the CagL/CagA positivity are susceptible to the risk of gastric cancer and DU, and the HLA-DQA1*05 (OR, 0.318) allele was suggested as a protective allele for the risk of gastric cancer and DU using univariate analyses. HLA-DQA1*01 (OR, 2.21), HLA-DQB1*06 (OR, 2.67), sex (male, OR, 2.27), and CagL/CagA/(<2) EPIYA C repeats (OR, 5.72) were detected independent risk factors that increased the risk of gastric cancer and DU using multivariate analyses. However, the HLA-DRB1*04 (OR, 0.28) allele was shown to be a protective allele, which decreased the risk of gastric cancer and DU. Gastric pathologies result from an interaction between bacterial virulence factors, host epigenetic and environmental factors, and H. pylori strain heterogeneity, such as genotypic variation among strains and variations in H. pylori populations within an individual host., Competing Interests: Declaration of Competing Interest The author(s) declare that there are no conflicts of interest, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: As a component of the cag T4SS, the cagL gene is involved in the translocation of CagA into host cells and is essential for the formation of cag PAI-associated pili between H. pylori and gastric epithelial cells., Aim: We aimed to investigate the clinical association of the cagL gene with other virulence factors (VacA, CagA, EPIYA-C, and BabA protein) of H. pylori strains isolated from GC, duodenal ulcer (DU), and non-ulcer dyspepsia (NUD) cases., Methods: The patient group (PG), including 47 patients (22 GC and 25 DU) and a 25 control group (CG= NUD) were included. Amplification of the H. pylori cagL, cagA, vacA, and babA2 genes and typing of EPIYA motifs were performed by PCR methods., Results: Sixty-one (84.7%) H. pylori strains were detected with cagL (93.6% in SG, 68% in CG). We detected a significant difference between SG and CG for the presence of cagL (p=0.012) but no statistical comparison was done for (≥2) EPIYA-C repeats In the comparison of H. pylori strains with cagA/vacAs1m1 and cagA/ vacAs1m2 and babA2 for the presence of cagL, we could not detect a significant difference (p=1)., Conclusion: We detected a significant difference between groups for the presence of cagL genotype (p=0.012). The vacAs1m1 (OR: 2.829), genotypes increased the GC and DU risk by 2.8 times, while multiple (≥2) EPIYA-C repeats incresed the GC and DU risk by 3.524 times. Gender (to be female) (OR: 0.454) decreased the GC and DU risk by inversly decreased in the multivariate analysis., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)

Background: Non Helicobacter pylori gastric Helicobacters (NHPGHs) are associated with a range of upper gastrointestinal symptoms, histologic and endoscopic findings. For the first time in Iran, we performed a cross-sectional study in order to determine the prevalence of five species of NHPGHs in patients presenting with dyspepsia., Methods: The participants were divided into H. pylori-infected and NHPGH-infected groups, based on the rapid urease test, histological analysis of biopsies, and PCR assay of ureA, ureB, and ureAB genes. The study included 428 gastric biopsies form dyspeptic patients, who did not receive any treatment for H. pylori. The samples were collected and sent to the laboratory within two years. H. pylori was identified in 368 samples, which were excluded from the study. Finally, a total of 60 non-H. pylori samples were studied for NHPGH species., Results: The overall frequency of NHPGH species was 10 for H. suis (three duodenal ulcer, three gastritis, and four gastric ulcer samples), 10 for H. felis (one gastritis, three duodenal ulcer, and six gastric ulcer samples), 20 for H. salomonis (four duodenal ulcer, five gastritis, and 11 gastric ulcer samples), 13 for H. heilmannii (three gastritis, five duodenal ulcer, and five gastric ulcer samples), and 7 for H. bizzozeronii (zero gastric ulcer, two duodenal ulcer, and five gastritis samples)., Conclusions: Given our evidence about the possibility of involvement of NHPGHs in patients suffering from gastritis and nonexistence of mixed H. pylori infection, bacteriological testing of subjects negative for H. pylori becomes clinically relevant and important. Our findings suggest H. salomonis has the highest rate among the NHPGH species in Iranian dyspeptic patients.

Background: IL-27 has dual roles in the immune response either stimulating Th1 or inhibiting Th17 cells. Because there is a particular link of IL-23/Th17 axis in the development of cancer and IL-27 has been considered a potential treatment for cancer, we evaluated the gastric and serum concentrations of IL-27 in two mutually exclusive Helicobacter pylori-associated diseases, gastric cancer (GC) and duodenal ulcer (DU)., Material and Methods: We prospectively studied 110 H pylori-positive patients and 40 healthy blood donors. Serum and gastric concentrations of IL-27 and cytokines of the Th1/Th17 cells were assessed by ELISA., Results: IL-27 was not detected in GC patients, but the cytokine concentration was very high in the patients with DU. IL-27 was also detected in the gastritis patients and in the H pylori-positive blood donors. IL27RA mRNA expression in peripheral blood mononuclear cells, evaluated by rt-PCR, was stimulated by H pylori strains. The cytokine concentration positively correlated with the Th1 and negatively with Th17 cell representative cytokine levels. Gastric IL-27 concentrations were positively correlated with increased degree of mononuclear and polymorphonuclear cells on the antral gastric mucosa of DU patients in consonance with the DU gastritis pattern. IL-12p70 and IFN-γ gastric concentrations were significantly higher in DU than in GC. Conversely, gastric concentrations of Th17 cell-associated cytokines (IL-1β, IL-6, IL-17A, IL-23, and TGF-β) were significantly higher in GC than in DU patients., Conclusion: Although H pylori infection is able to elicit IL-27 and IL-27Rα secretion, DU and GC have diametrically opposed cytokine patterns., (© 2019 John Wiley & Sons Ltd.)

Heterotopic gastric mucosa in the duodenal bulb is a rare congenital disorder with varied clinical presentations. The mechanism of formation of a duodenal ulcer is failure of balance of the attack factor and the defense factor, which is the same as the mechanism of formation of a gastric ulcer. However, the true etiology of the duodenal ulcer remains unknown. Gastric mucosa can secrete gastric juice which injures itself, but the duodenal mucosa does not contain cells secreting a digestive enzyme. We assume that duodenal ulcers are caused by the presence of heterotopic gastric mucosa that can secrete gastric acid. This study was designed to assess the prevalence and associations of heterotopic gastric mucosa in duodenal ulcers. The present study included 137 patients who underwent biopsy or resection of duodenal ulcer. We detected gastric foveolar metaplasia due to inflammation from a heterotopic gastric mucosa using immunohistochemical staining. Heterotopic gastric mucosa consists of foveolar epithelium (MUC5AC-positive) and fundic gland (H⁺K⁺ ATPase-positive parietal cells, pepsinogen I-positive chief cells and MUC6-positive mucous neck cells), whereas gastric metaplasia is composed of foveolar epithelium without fundic glands. These specimens were stained with toluidine blue for detection of Helicobacter pylori infection. Among the 137 patients with duodenal ulcer, 76 cases (55%) had heterotopic gastric mucosa in the obtained specimens, and Helicobacter pylori was found in 45 cases (59%,45/76) among those with heterotopic gastric mucosa. Our results suggest that heterotopic gastric mucosa was strongly associated with concurrent duodenal ulcer.

This study aimed to investigate the intestinal microbiota in duodenal ulcer (DU) patients, effects of proton pump inhibitors,clarithromycin and amoxicillin, PCA) for Helicobacter pylori (H. pylori) and Bacillus subtilis and Enterococcus faecium (BSEF) on intestinal microbiota. DU patients were randomly assigned to receive either PCA (group TT) or PCA plus BSEF(group TP). The fecal microbiome was conducted using high throughput 16S rDNA gene and internal transcribed spacer sequencings. The diversity and abundance of intestinal bacteria in the DU were significantly lower than health check control (HC) group. In the TT group, the abundance and diversity of both intestinal bacteria and fungi decreased after PCA treatment, compared with those before treatment, whereas in the TP group no obvious changes were observed. In the TT group at all the time points, both the intestinal bacteria and fungi were different from those in the HC group. However, in the TP group, at 10w the bacterial flora abundance was close to that in the HC group. The results indicate that anti- H. pylori treatment induced significant decrease in the diversity of intestinal microbiota, while the combined therapy supplemented with BSEF could protect and restore the intestinal microbiota.

The association between obesity and peptic ulcer disease (PUD) is inconclusive. To evaluate the association of obesity and metabolically healthy obesity (MHO) with PUD risk, we performed a retrospective cohort study of 32,472 subjects without PUD at baseline who underwent repeated health examinations. Participants were stratified by body mass index (BMI) and metabolically healthy state. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard modelling. During the follow-up period, 1940 PUD cases occurred. PUD, particularly gastric ulcer (GU), had significantly higher cumulative incidence in obese subjects compared to non-obese subjects ( p value < 0.001). The HR for developing GU was 1.32 (95% CI, 1.16-1.49; p value <0.001); after adjusting for confounding factors (lifestyle, metabolic, and Helicobacter pylori status), the association was no more significant ( p value = 0.789). For duodenal ulcer (DU), cumulative incidence between obese and non-obese groups was not significantly different ( p value = 0.464). The risk of developing DU in the obese group was not significantly different from the non-obese group (HR 0.95; 95% CI, 0.83-1.09; p value = 0.469) and consistently showed no association after adjusting for metabolic parameters ( p value = 0.199). Furthermore, MHO subjects had no increase in GU or DU risks. In this large cohort study, PUD risk was not associated with obesity or MHO., Competing Interests: The authors declare no conflict of interest.

Helicobacter pylori positivity was assessed among 656 symptomatic children in 2010-2017. Overall infection prevalence was 24.5% and a significantly higher rate was detected in girls (28.5%) compared to boys (20.0%). Moreover, in children with duodenal ulcer, H. pylori prevalence was higher (47.4%) compared with the rest (23.9%). On the contrary, the infection was detected 1.9-fold less frequently in patients with GERD (14.5%) compared with the other (27.0%) patients and 2.1-fold less often in the presence of duodenogastric reflux (bile) reflux (13.0%) compared with the absence of the reflux (27.0%). No significant difference was observed between the younger (aged ≤7 years, 20.0%) and the older (aged 8-18 years, 25.5%) patients. H. pylori infection rate in Bulgarian pediatric patients between 2010 and 2017 was 2.5-fold lower than that in 1996-2006. In conclusion, H. pylori infection is still an important concern for Bulgarian children, although having decreased by about 1.8%/yearly over 21 years. This study reveals the importance of H. pylori diagnostics even in the youngest symptomatic children and demonstrates an inverse association between either GERD or bile reflux and H. pylori infection.

Aim: To assess the prevalence of the lesions in duodenal bulb mucosa and the relationship between duodenal lesions and upper gastrointestinal diseases, including helicobacter pylori infection., Methods: Clinical, endoscopic and pathological data of the cases with duodenal bulb and gastric mucosal biopsy from January 2005 to May 2017 were analyzed retrospectively., Results: A total of 3540 patients were enrolled. The biopsy from protuberant lesions with endoscopic morphology are mostly duodenal gastric heterotopia or adenoma. The biopsy from duodenal ulcers are often observed in inflammatory changes and gastric metaplasia. Patients with gastric heterotopia had a significantly lower prevalence of chronic atrophic gastritis, intestinal metaplasia, and gastric ulcer; and much higher prevalence of gastroesophageal reflux disease and gastric fundic polyps. Patients with gastric metaplasia had been positively associated with gastroesophageal reflux disease, and negatively associated with gastric fundic polyps. There were positive correlation between helicobacter pylori infection and duodenal active inflammation, Brunner gland hyperplasia, gastric metaplasia and duodenal ulcer. However, Patients with gastric heterotopia in bulb had been negatively associated with helicobacter pylori infection., Conclusions: The mucosa lesions in duodenal bulb were associated with concurrent gastric fundic gland polyps, gastroesophageal reflux disease, duodenal ulcer, and helicobacter pylori infection., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Peptic ulcer disease is a condition in which an important role has infection with H. pylori. The most common complication of peptic ulcer is bleeding. The presence of H. pylori triggers local and systemic cytokine signaling which may affect processes such as healing, gastric or duodenal rupture, and carcinogenesis. In this study, we examined the concentrations of IL-1β, IL-6, IL-10, TNF, TGF-β and IL-17A in serum by enzyme immunoassay and their mRNA expressions in periulcer biopsies obtained from patients with bleeding peptic ulcer by means of real-time-PCR., Results: We have shown that pro-inflammatory IL-6 and TNF concentrations in serum were significantly higher in patients who were infected with H. pylori, while the concentrations of TGF-β and IL-17A were significantly lower compared to non-infected subjects. IL-17A expression in periulcer mucosa was significantly higher in patients who were infected with H. pylori, while the expression of other cytokines, there was no significant difference compared to non-infected controls. Considering higher serum concentrations in non-infected subjects and higher IL-17A expression in mucosal tissue of infected patients, our data support the studies that found IL-17A has protective role in eradication of H. pylori infection in infected patients.

Background and Aims: Costa Rica is one of the countries with the highest incidence and mortality rates for gastric cancer. Helicobacter pylori infection rates are high in the whole country. We have previously shown that H. pylori CagA+ is significantly associated with atrophic gastritis (AG) of the antrum in a dyspeptic population. The aim of this work is to determine if other H. pylori virulence factors (vacA, dupA, oipA, iceA and babA2) are associated with atrophic gastritis (AG) or duodenal ulcer (DU)., Methods: The presence of virulence genes in Costa Rican H. pylori isolates was analyzed by PCR in 151 cultured strains from patients with dyspeptic symptoms. Endoscopic and histopathological diagnoses were available. Odds-ratio and 95% confidence intervals for AG patients vs. non-atrophic gastritis (NAG) or DU patients vs. no duodenal ulcer (NDU) patients were calculated., Results: Amongst the studied isolates, 82% had the cagA + , 76.2% had the vacA s1m1, 97.0% had the oipA + , 21.0% had the icea1, 79.0% had the iceA2, 44.0% had the babA2 + and 76.0% the dupA + genotypes. Infection with H pylori cagA + , dupA + , oipA + , iceA, babA2 + , and vacA s1m1 genotypes was not associated with AG risk. The frequency of the dupA gene was 78.7 and 60.9% in isolates from patients with NDU and DU, respectively, and its presence was significantly associated with decreased risk of duodenal ulcer [odds-ratio: 0.33, p = 0.024, confidence interval 95% (0.11-0.85)]., Conclusion: H. pylori dupA genotype is inversely associated with DU risk in this population., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Emerging studies have shed light on the association between Helicobacter pylori (HP) infection and cardiometabolic risk. However, there is no evidence to support a causal link for the relationship in the general population. Our aim was to determine whether HP infection is associated with the risks of incident type II diabetes mellitus (DM) in a population-based cohort consisting of adults from the general population. A total of 69235 adults enrolled in the study obtained health examinations at the Tri-Service General Hospital in Taiwan from 2010 to 2016. HP infection detection was performed by rapid urease tests (RUTs), and endoscopic examinations were used to diagnose gastroesophageal reflux disease (GERD), gastric ulcers (GUs) and duodenal ulcers (DUs). Cross-sectional and longitudinal analyses were performed to examine the association between HP infection and cardiometabolic diseases using logistic regression and Cox regression in a large population-based study. HP infection was significantly associated with the presence of metabolic syndrome (MetS) (OR = 1.26, 95%CI: 1.00-1.57) and DM (OR = 1.59, 95%CI: 1.17-2.17) only in male subjects, and abnormal endoscopic findings were also correlated with cardiometabolic diseases. Our findings demonstrated that participants with HP infection had an elevated risk of developing incident DM (HR = 1.54, 95%CI: 1.11-2.13). In addition, endoscopic findings of a DU (HR = 1.63, 95%CI: 1.02-2.63), rather than GERD or a GU, were also predictive of incident DM. In this cohort, HP infection was a statistically significant predictor of incident DM among male population., Competing Interests: The authors have declared that no competing interests exist.

Background: The aim of this study was to identify the common H. pylori virulence genes among dyspeptic Southwestern Saudi patients and their association with clinical outcomes and histopathological findings to help practitioners and researchers in the region for better management of infections caused by such bacteria., Methods: Four hundred two gastric biopsy specimens were analyzed using histopathological examination and real time-PCR. The positive 187 specimens by RT-PCR were genotyped using PCR targeting cagA, vacA and iceA genes., Results: One hundred twenty-eight gastric biopsy specimens were positive in genotyping PCRs. The cagA, vacA, iceA1 and iceA2 genes were detected in rates of 49.2% (63/128), 100%(128/128), 42.2% (54/128), 32.8% (42/128), respectively. The vacA s1as1bm2 subtype was the highest 23.4% (30/128), followed by m2 and s1a1b subtypes which were equally detected [16.4% (21/128) for each]. The iceA genes were significantly associated with gastritis and gastric ulcer. Overall, vacA genotypes were significantly associated with gastritis, gastric and duodenal ulcers. The vacA subtypes: s1as1bm2, s1a1b and s2 m2 showed chronic active gastritis in percentages of 90.0, 81, and 84.2%, respectively. All vacA mixed genotypes showed chronic active gastritis., Conclusions: H. pylori virulence genes are highly prevalent and diverse among patients with dyspepsia in Southwestern region of Saudi Arabia. The iceA genes and the different vacA subtypes are significantly associated with the clinical outcomes and histopathological changes especially chronic active gastritis.

Interactions between Helicobacter Pylori (HP) and gastroesophageal reflux disease (GERD) are a complex issue. Several pathophysiological factors influence the development and the course of GERD, HP infection might be only one of these. Many studies emphasize the co-existence of these diseases. HP infection could contribute to GERD through both a protective and an aggressive role. Gastric acid secretion is a key factor in the pathophysiology of reflux esophagitis. Depending on the type of gastritis related to HP, acid secretion may either increase or decrease. Gastritis in corpus leads to hypoacidity, while antrum gastritis leads to hyperacidity. In cases of antral gastritis and duodenal ulcers which have hyperacidity, the expectation is an improvement in pre-existing reflux esophagitis after eradication of HP. In adults, HP infection is often associated with atrophic gastritis in the corpus. Atrophic gastritis may protect against GERD. Pangastritis which leads to gastric atrophy is commonly associated with CagA strains of HP and it causes more severe gastric inflammation. In case of HP-positive corpus gastritis in the stomach, pangastritis, and atrophic gastritis, reflux esophagitis occurs frequently after eradication of HP. Nonetheless, as a predisposing disease of gastric cancer, HP should be treated. In conclusion, as the determinative factors affecting GERD involving in HP, detailed data on the location of gastric inflammation and CagA positivity should be obtained by the studies at future.

Helicobacter pylori induces chronic gastritis and duodenal ulcer in a small fraction of the colonised population. Three decades after the discovery of H. pylori and disclosure of an urgent need for eliminating the bacterium in patients, it seems that we are still in the first steps of dealing with this mysterious organism. Treatment of H. pylori is a complex dilemma for clinicians, a repeating sentence by many scientists who spend years on this research topic. Apart from many modifications in initial first-line treatment of H. pylori, gastroenterologists are unable to overcome the problem of therapeutic failure. Choosing the best regimen in any region depends on many factors, which have been the focus of many randomised clinical trials. A potential increase in efficacy of future therapies may be influenced by adding the novel potassium-competitive acid blocker vonoprazan. Undeniably, in-depth analysis is necessary to propose more effective therapeutic regimens. Meanwhile, we recommend the performance of antimicrobial susceptibility testing before any antimicrobial prescription., (Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

Fitz-Hugh-Curtis syndrome (FHCS) is characterized by perihepatic and pelvic inflammation and occurs mostly in women of childbearing age. Here, we report a case of FHCS caused by Chlamydia trachomatis in a 50-year-old man. The patient presented to our hospital with right upper quadrant abdominal pain, and enhanced computed tomography revealed perihepatic and pelvic free fluid and early-phase hepatic capsular enhancement. A urine specimen was positive for Chlamydia trachomatis. The patient was diagnosed with FHCS due to Chlamydia trachomatis infection. In conclusion, FHCS cannot be excluded when men present with right upper quadrant abdominal pain without significant signs of biliary tract disease.

Aim: To evaluate the efficacy and tolerability of tetracycline vs. high-dose amoxicillin in bismuth-based quadruple therapy for Helicobacter pylori(H. pylori) eradication., Methods: This randomized, open-label clinical trial included 228 patients with H.pylori infection and duodenal ulcer without a history of H.pylori treatment. Patients were randomly divided into two groups. The amoxicillin group received metronidazole 500mg, bismuth subcitrate 240mg, and amoxicillin 1000mg, all three times a day, plus omeprazole 20 mg twice a day, for 14 days. The tetracycline group received metronidazole 500mg three times a day; bismuth subcitrate240mg and tetracycline HCl 500mg, both four times a day; and omeprazole 20 mg twice a day, for 14 days. Evaluation for compliance and drug-relatedadverse effects were evaluated at the end of two weeks. Eight weeks after the end of treatment, the rate of H.pylori eradication was assessed by the C13urease breath test., Results: There were no significant demographic differences between the two groups. Eradication rate was higher with the amoxicillin-containing regimen than the tetracycline-containing regimen: 105/110 (95.51%; 95% confidence interval, 91.5%-99.3%) vs. 88/105 (83.8%; 95%CI, 76.7%-90.8%) by per-protocol analysis (p = 0.005) and 92.9% (95%CI, 88.1%-97.6%) vs. 76.5% (95%CI, 68.7%-84.2%) by intention-to-treat analysis (ITT, p = 0.001). Adverse effects were significant higher in the tetracycline groupthan in the amoxicillin group (65.2% vs. 43.4%; p = 0.001)., Conclusion: Bismuth-based quadruple therapy including high-dose amoxicillin and metronidazole achieved an acceptable rate of H.pylori infection eradication with good tolerance in patients with duodenal ulcer. This regimen can overcome treatment resistance in areas with high prevalence of metronidazole and clarithromycin resistance., Trial Registration: The Thai Clinical Trial Registry (TCTR) 20170623004., Competing Interests: The authors have declared that no competing interests exist.

Background and Aims: The prevalence of Helicobacter pylori (H. pylori) tends to be lower in Western countries such as central Europe compared with Asia. The virulence of H. pylori is influenced by its subtype composition, most importantly by the presence or absence of different types of cytotoxin-associated gene A(CagA). This study aimed to assess the prevalence of H. pylori and its respective CagA phenotype in a large retrospective cohort of patients with gastric cancer or duodenal ulcer at a Western tertiary referral institution., Methods: H. pylori positive gastric biopsy samples from patients diagnosed with the afore mentioned diseases within the past 25 years were re-evaluated by histology for H. pylori and status of gastritis. Confirmed H. pylori positive cases were processed for immunohistochemistry (IHC) for H. pylori,CagA, and EastAsiantype CagA., Results: The prevalence of H. pylori positive gastric biopsy samples decreased from 20.7% to 2.3% within the study period. Among the gastric cancer patients, the H. pylori positive rate was 16.6%, and didn't show significant changes over time (p = 0.38). Contrary, the H. pylori positive rate of duodenal ulcer decreased significantlyfrom 40% to 5% (p = 0.01). Within H. pylori positive groups ofboth diseases, CagA was highly detected at IHC (86% and 78%, respectively). Except for a few patients originating from East Asian countries, all CagA detected in this study were of Western type., Conclusion: In this first Western investigation on the chronological prevalence of H. pylori and its most relevant subtypes, Western type of CagA was highly detected in two important index diseases of the pathogen. This raises further questions about the virulence of this subtype., Competing Interests: The authors have declared that no competing interests exist.

Objective: To identify and compare the bacterial community profile of mucosal tissues from a gastric antrum ulcer and a duodenal ulcer in Helicobacter pylori ( Hp ) positive dyspeptic patients. Methods: Genomic DNA was extracted from the mucosal tissues obtained from 18 patients diagnosed with gastric antrum or duodenal ulcers. A library was constructed using 16S rRNA gene amplification, and Miseq high-throughput sequencing was used to analyse the amplified products. Bioinformatics methods, including operational taxonomic units (OTUs), hierarchical clustering, and a diversity analysis, were performed to investigate and characterize the community composition. Results: The proportion of Helicobacter in the mucosa of patients with a gastric antrum ulcer was significantly higher than that of patients with a duodenal ulcer. However, the diversity of the bacterial community in the gastric antrum ulcer mucosa was significantly lower compared with the mucosa of the duodenal ulcer. There were significant differences in microbial community structure between the gastric antrum ulcer and the duodenal ulcer. Notably, Helicobacter, Prevotella, Neisseria , and Streptococcus were also predominant genera in the bacterial community of the duodenal ulcer mucosa, and they outnumbered those species in gastric antrum ulcer mucosa. Conclusion: The bacterial community composition and the corresponding abundance differ between the mucosal tissues of Hp positive gastric antrum ulcer and duodenal ulcer patients. Additionally, the bacterial community diversity in the mucosal tissues from gastric duodenal ulcer patients is higher than that from gastric antrum ulcer patients, and Helicobacter is not the absolutely predominant genus.

Background: The association between infection with Helicobacter pylori and different gastroduodenal diseases is related to bacterial, host and environmental factors. Studies have demonstrated an association between the genetic diversity of H. pylori, especially in the vacA and cagA genes, and the development of digestive diseases such as peptic ulcer and gastric cancer. In addition, the nature of the host inflammatory response may explain these different manifestations of infection caused by this microorganism. In this respect, host factors that regulate the immune and inflammatory responses involving the functional interaction of H. pylori infection with different components of the immune system, particularly T cells, in gastroduodenal diseases still need further investigation., Objective: To characterize the immune response, including immunity induced by infection with H. pylori, especially virulent strains (vacA alleles and cagA gene), by analyzing the cytokine profile and T-cell population present in gastroduodenal diseases in a Brazilian population., Methods: In a prospective study, gastric biopsies were collected from 554 patients with different gastroduodenal diseases for histological analysis and for the determination of bacterial genotype and cytokine production (IL-4, IL-10, IFN-γ and IL-12) by ELISA., Results: The predominant genotype of the H. pylori strains isolated from the patients studied was s1m1cagA+, which was more common among patients with gastric ulcer, duodenal ulcer and gastric cancer. A significant association was observed between the s1m1cagA+ genotype and a higher degree of inflammation, higher neutrophil activity and the development of intestinal metaplasia. The gastric concentrations of IFN-γ and IL-12 were significantly higher in patients infected with H. pylori than in uninfected individuals. Higher levels of these cytokines were detected in patients with gastric ulcer and cancer, while the levels of IL-4 and IL-10 in the gastric mucosa were lower in these patients. In addition, IFN-γ and IL-12 concentrations in gastric biopsies were higher in patients infected with the virulent s1m1cagA+ genotype. In contrast, IL-4 and IL-10 levels were higher in tissue infected with s2m2cagA in gastric biopsies., Conclusion: Our study shows that the interaction between the type of infectious strain and the Th1 immune response can influence and perpetuate gastric inflammation, and thus contributes to the development of the different clinical manifestations of H. pylori infection.

Introduction: Helicobacter pylori, a water contaminant, is the primary pathogenic agent associated with gastric diseases in humans. Exposure to H. pylori is more likely higher in developing countries. This study aimed to evaluate the risk factors associated with H. pylori infection in patients undergoing endoscopy to validate the cause of dyspeptic symptoms in an urban population in northeast Brazil and to compare the urease test and polymerase chain reaction assay results with the histopathological findings., Methods: We evaluated 200 of 759 individuals with dyspeptic complaints from Campina Grande, State of Paraiba, northeast Brazil. Patients underwent endoscopy, followed by gastric biopsies. Logistic regression analysis was performed to adjust for confounders and to determine significant risk factors of dyspeptic disorders., Results: Women accounted for 72.5% (145/200) of the participants. Approximately 59.8% (120/200) of the samples tested positive for H. pylori based on histological examinations. The specificity of polymerase chain reaction assay was higher than that of the urease test (77% vs. 64%, p=0.034). City drinking water [odds ratio (OR): 2.6; 95% confidence interval (CI): 1.3-5.21; p=0.004] and smoking (OR: 4.0; 95% CI: 1.13-14.5; p=0.031) were the risk factors of H. pylori infection. Belching was the most common symptom associated with H. pylori infection (p=0.05)., Conclusions: The increased risk of H. pylori infection associated with non-treated water consumption indicates the need for improvements in public water treatment and better sanitary conditions because these can be a source of not only H. pylori infections but also other water-borne pathogen infections.

Background: Helicobacter pylori infection is a known risk factor for duodenal ulcers, gastritis, and gastric cancer. The eradication of H. pylori is successful in treating these disorders; however, the success rate of eradication therapy is declining. There may be an interaction with nutrient intake to account for this decline. Objective: We investigated the influence of food and nutrient intake on H. pylori eradication therapy. Design: In this study, 4014 subjects underwent endoscopy, were tested for serum antibodies to H. pylori (2046 positive; 51.0%), and had their food intake assessed with the use of a food-frequency questionnaire (FFQ). Of the positive subjects, endoscopies showed that 389 (19.0%) had gastritis and/or duodenal ulcers and were also positive for a 13 C-urea breath test (UBT). These 389 subjects received 1-wk H. pylori eradication therapy with lansoprazole, amoxicillin, and clarithromycin and a second UBT 8 wk after treatment. Complete demographic characteristics, serum lipid, insulin, glycated hemoglobin, C-reactive protein (CRP), and creatinine concentrations as well as complete FFQs were available for 352 subjects. Multivariate logistic regression analyses were performed to determine factors that were associated with successful H. pylori eradication therapy. Results: The success rate of eradication therapy was 60.4% (235 of 389). Factors associated with the failure of eradication therapy included increased age ( P = 0.02), higher CRP concentrations ( P < 0.01), higher dietary cholesterol ( P < 0.01) or egg intake ( P < 0.01), higher ω-3 (n-3) fatty acid ( P = 0.02) or fish intake ( P = 0.01), and higher vitamin D intake ( P = 0.02). Moreover, the higher vitamin D intake was strongly linked to higher fish intake. A limitation of the study is that we did not assess the antibiotic resistance of H. pylori Conclusions: Our results indicate that higher egg and fish intake may be negatively correlated with successful H. pylori eradication therapy in H. pylori -positive subjects with gastritis and/or duodenal ulcers., (© 2017 American Society for Nutrition.)

Background: Helicobacter pylori infection is prevalent in Ghana. The development of gastro-duodenal disease is dependent on virulence of the infecting strain, host susceptibility and environmental factors. Helicobacter pylori cagA and vacA strains induce more inflammation, ulceration and oncogenesis. Here, for the first time we present data on H. pylori cagA and vacA genes and their association with gastro-duodenal disease in Ghana. A total of 159 patients with dyspepsia at Korle-Bu Teaching Hospital, Accra, were investigated for H. pylori with urease-CLO, of which 113 (71.1%) were positive. Genomic DNA was extracted from antral biopsies using QIAGEN DNeasy kit. Detection of H. pylori vacA and cagA genes were determined by PCR as previously described., Results: In total, 110 (69.2%) vacAs1, 71 (44.7%) vacAm1, 35 (22.0%) vacAm2, 77 (48.4%) cagA-(hydrophilic region) and 109 (68.6%) cagA-(internal duplication region) were detected. In multivariate analysis, duodenal ulcer was more likely than other diagnoses to have detectable cagA-(hydrophilic region) (OR 3.1 CI 1.2-7.9) or vacAs1m1 (OR 6.5 CI 1.2-34.0)., Conclusions: Majority of biopsies were colonized with H. pylori harboring both cagA and vacA. H. pylori cagA-(internal duplication region) was more prevalent than cagA-(hydrophilic region). Duodenal ulcer was more likely than other diagnoses to have detectable cagA-(hydrophilic region) or vacAs1m1.

Background: Jianzhong decoction is widely used to treat peptic ulcers; however, due to lack of systematic evaluations, its clinical efficacy remains controversial. We performed meta-analysis to evaluate the efficacy and safety of Jianzhong decoction in treating peptic ulcers., Methods: Studies were systematically retrieved from PubMed, Embase, Cochrane library, China National Knowledge Infrastructure, Wanfang Database, Chongqing VIP, China Biology Medicine disc (CBMdisc), and references cited in related studies/reviews. Extracted data included the total effective rate, helicobacter pylori eradication rates, recurrence rate, and adverse reaction rate. Fifty-eight randomised controlled trials involving 5192 patients were included in the final analysis., Results: Results showed that Jianzhong decoction therapy was more effective than conventional Western medicine therapy (total effective rate, odds ratio [OR] = 4.29, 95% confidence interval [CI]: 3.51-5.23, P = 0.000; helicobacter pylori eradication rates, OR =2.10, 95% CI: 1.69-2.61, P = 0.000; recurrence rate, OR =0.23, 95% CI: 0.18-0.29, P = 0.000; and adverse reaction rate, OR =0.20, 95% CI: 0.12-0.33, P = 0.000)., Conclusions: Jianzhong decoction increased the total effective rate and helicobacter pylori eradication rate, and lowered the recurrence and adverse reaction rates. The results of this study can be used as a guide for clinical treatment of peptic ulcers.

Helicobacter pylori (H. pylori) infection induces inflammation of the gastric mucosa, which may progress to precancerous lesions leading to gastric cancer. Pathological determinism is associated to some virulence genes of the bacterium, notably the vacA and cagA genes. The present study aimed to determine the H. pylori genotypes distribution and their association with sex, age and gastric diseases in a Moroccan population. Gastric biopsy was taken from 1079 consenting patients. The specimens were processed by PCR to identify H. pylori and to determine the genotypic profile by PCR characterizing vacA s, vacA m and vacA i regions directly from biopsies H. pylori positives. VacA genotyping revealed the predominance of vacA m2 (53.2%), vacA s2 (52.9%) and vacA i2 (52%). The most virulent vacA alleles (s1, i1 and m1) are more predominant in men (47.3%, 41.9% and 46.1% respectively) than in women (38.3%, 33.3% and 37% respectively). However, the association between vacA genotypes and age did not reach a statistical significant value. Logistic regression analysis results show that vacA i1m1 and vacA i1m2 genotypes were strongly associated with the risk of GC, the Odds Ratio (95% confidence interval) was 29.73 [5.08-173.73] and 9.17 [2.06-40.82] respectively, while vacAs1/cagA+ seems to be a risk factor for DU since it is inversely associated with GC (OR was 0.13 [0.02-0.75]. The results of this study suggest that vacA i1 genotype independently to vacAm status may be of a clinical usefulness and will help to identify patients at a high risk of GC development., Competing Interests: The authors have declared that no competing interests exist.

Background: To prevent gastric cancer, a test-and-treat strategy for Helicobacter pylori has been proposed. This retrospective study assessed the clinical features, efficacy and safety of treatment for H. pylori infection in children and adolescents., Methods: Questionnaires concerning the clinical features and treatment of H. pylori in children and adolescents were sent to doctors in 2013. It included questions on patient background, H. pylori-associated disease, first- and second-line treatment, success or failure of eradication, resistance to antibiotics, and occurrence of adverse events. In 2014, serious adverse events associated with treatment were analyzed., Results: Invitation letters and questionnaires were sent to 1097 doctors, of whom 409 (37.3%) participated. Finally, 332 patients (mean age, 11.6 ± 3.4 years; male, n = 200) treated from 1997 to 2013 were analyzed. H. pylori-associated gastritis, iron deficiency anemia, and duodenal ulcer occurred most frequently. Success rates for first- and second-line treatments were 73.1% and 79.6%, respectively. Seventy-six H. pylori strains were analyzed for resistance to amoxicillin (AMPC) and clarithromycin (CAM), and 64 were analyzed for resistance to metronidazole (MNZ). CAM resistance was most frequent, occurring in 43.4% of patients; that of MNZ was 21.9%. Adverse events were observed in 13.8% of cases. In total, 587 cases of H. pylori infection were analyzed and no serious adverse events were observed., Conclusions: Treatment for H. pylori in children and adolescents is safe, but further studies on treatment regimens should be conducted to improve eradication rates and monitor increasing CAM resistance., (© 2016 Japan Pediatric Society.)

Background: Non-Helicobacter pylori-helicobacters (NHPH) compose a group of gram negative zoonotic bacteria that may induce in humans gastric diseases including gastritis, gastroduodenal ulcer and MALT lymphoma. Their prevalence in the general population has previously been reported to 0.1-6.2%, although such reports still remain less in number., Aims: This study aimed at estimating the prevalence of gastric NHPH in Japanese people, and further aimed at linking this to different gastric diseases and co-infection with H. pylori., Methods: Endoscopically obtained biopsy samples from 280 Japanese patients with various gastric diseases were collected. Samples were analyzed by immunohistochemistry and by species-specific PCR for detection of gastric helicobacters., Results: The total prevalence of gastric NHPH among 280 Japanese patients was 6.1%, and the prevalence of H. pylori was 65.7%. There was no significant difference in prevalence of either NHPH or H. pylori when infected with H. pylori or NHPH, respectively. NHPH infection was found to be the highest in patients with gastric MALT lymphoma and duodenal ulcer, the former being independent of co-infection with H. pylori and the latter being dependent., Conclusions: This study reports a total prevalence of 6.1% of gastric NHPH in Japanese patients, and further highlights gastric MALT lymphoma and duodenal ulcer (when co-infected with H. pylori) as important related diseases., (© 2016 S. Karger AG, Basel.)

Helicobacter pylori ( H. pylori ) is a gastric human pathogen associated with acute and chronic gastritis, 70% of all gastric ulcers, 85% of all duodenal ulcers, and both forms of stomach cancer, mucosal-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Recently, attention has focused on possible relationship between presence of certain virulence factor and H. pylori -associated diseases. Some contradictory data between this bacterium and related disorders has been observed since not all the colonized individuals develop to severe disease. The reported diseases plausibility related to H. pylori specific virulence factors became an interesting story about this organism. Although a number of putative virulence factors have been identified including cytotoxin-associated gene a ( cagA ) and vacA , there are conflicting data about their actual participation as specific risk factor for H. pylori -related diseases. Duodenal ulcer promoting gene a ( dupA ) is a virulence factor of H. pylori that is highly associated with duodenal ulcer development and reduced risk of gastric cancer. The prevalence of dupA in H. pylori strains isolated from western countries is relatively higher than in H. pylori strains from Asian countries. Current confusing epidemiological reports will continue unless future sophisticated and molecular studies provide data on functional and complete dupA cluster in H. pylori infected individuals. This paper elucidates available knowledge concerning role of dupA in virulence of H. pylori after a decade of its discovery., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article.

Helicobacter pylori (H. pylori ) infection is a major cause of chronic gastritis and is highly related to duodenal ulcer (DU) and gastric cancer (GC). To identify H. pylori-related GC biomarkers with high seropositivity in GC patients, differences in levels of protein expression between H. pylori from GC and DU patients were analyzed by isobaric tag for relative and absolute quantitation (iTRAQ). In total, 99 proteins showed increased expression (>1.5-fold) in GC patients compared to DU patients, and 40 of these proteins were categorized by KEGG pathway. The four human disease-related adhesin identified, AlpA, OipA, BabA, and SabA, were potential GC-related antigens, with a higher seropositivity in GC patients (n = 76) than in non-GC patients (n = 100). Discrimination between GC and non-GC patients was improved using multiple antigens, with an odds ratio of 9.16 (95% CI, 2.99-28.07; p < 0.0001) for three antigens recognized. The optimized combination of OipA, BabA, and SabA gave a 77.3% correct prediction rate. A GC-related protein microarray was further developed using these antigens. The combination of OipA, BabA, and SabA showed significant improvement in the diagnostic accuracy and the protein microarray containing above antigens should provide a rapid and convenient diagnosis of H. pylori-associated GC.

Background: BabA is a Helicobacter pylori cell surface adhesin, which binds to the ABO/Le(b) histo-blood group antigens (Le(b)) and serves as a virulence factor., Methods: H. pylori single colonies were isolated from 156 [non-ulcer dyspepsia (NUD) = 97, duodenal ulcer (DU) = 34, gastric cancer (GC) = 25)] patients. babA and babB genes were evaluated by gene/locus-specific PCR. BabA protein expression and Le(b) binding activity were determined by immunoblotting and ELISA, respectively., Results: The combined categorization of H. pylori strains based on high, low or no levels of BabA expression and Le(b) binding, produced 4 groups: (I) BabA-high/Le(b)-high (36 %), (II) BabA-low/Le(b)-low (26 %), (III) BabA-neg/Le(b)-low (30 %) and (IV) BabA-neg/Le(b)-neg (8 %) strains. The majority (63 %) of the BabA-low/Le(b)-low strains exhibited mixed babA/B genotypes as compared to merely 18 % of the BabA-high/Le(b)-high, 15 % of the BabA-neg/Le(b)-neg and 11 % of the BabA-neg/Le(b)-low (P = 0.0001) strains. In contrast to NUD strains, the great majority (70 %) of DU strains were BabA-low/Le(b)-low (11 %, P = 0.0001), which compared to NUD strains, enhanced the risk of DU by 18.8-fold. In parallel, infection with babA/B mixed genotype strains amplified the risk of DU by 3.6-fold (vs. babA-positive: P = 0.01) to 6.9-fold (vs. babA-negative: P = 0.007)., Conclusions: Here, we show higher prevalence of mixed babA/B genotypes among BabA-low/Le(b)-low clinical strains. Recombination of babA and babB genes across their loci may yield lower BabA expression and lower Le(b) binding activity. We conclude that H. pylori strains with lower Le(b) binding activity are better adapted for colonization of the gastric metaplastic patches in the duodenum and enhance the risk of duodenal ulcers.

Background: Infection with Helicobacter pylori is associated with severe digestive diseases including chronic gastritis, peptic ulcer disease, and gastric cancer. Successful eradication of this common gastric pathogen in individual patients is known to prevent the occurrence of peptic ulcer disease and gastric cancer., Discussion: With half of the world's population being infected with H, pylori and only few antibiotics result in an effective eradication, a successful antibiotic driven worldwide eradication program seems unlikely. In addition, H. pylori eradication is not always beneficial as it has been described that eradication can be associated with an increased frequency of other disorders such as pediatric asthma, inflammatory bowel diseases and Barrett's Esophagus. We have to accept that eradication of this infection is a two-edged sword that is both useful and harmful and we should therefore focus our H. pylori eradication policy toward selectively identify and destroy only the virulent strains., Conclusion: In order to still be able to effectively treat H. pylori infections in the future we need an alternative diagnostic/treatment algorithm. This would involve a shift towards more precise and enhanced disease predicting diagnosis that tries to identify patients with chance of developing severe diseases such as gastric cancer, rather than the current regime that is geared towards find and destroy all H. pylori.

Objectives: Comparison of Helicobacter pylori eradication rates, side effects, compliance, cost, and ulcer recurrence of sequential therapy (ST) with that of concomitant therapy (CT) in patients with perforated duodenal ulcer following simple omental patch closure., Methods: Sixty-eight patients with perforated duodenal ulcer treated with simple closure and found to be H. pylori positive on three months follow-up were randomized to receive either ST or CT for H. pylori eradication. Urease test and Giemsa stain were used to assess for H. pylori eradication status. Follow-up endoscopies were done after 3 months, 6 months, and 1 year to evaluate the ulcer recurrence., Results: H. pylori eradication rates were similar in ST and CT groups on intention-to-treat (ITT) analysis (71.43% vs 81.80%,P = 0.40). Similar eradication rates were also found in per-protocol (PP) analysis (86.20% vs 90%,P = 0.71). Ulcer recurrence rate in ST groups and CT groups at 3 months (17.14% vs 6.06%,P = 0.26), 6 months (22.86% vs 9.09%,P = 0.19), and at 1 year (25.71% vs 15.15%,P = 0.37) of follow-up was also similar by ITT analysis. Compliance and side effects to therapies were comparable between the groups. The most common side effects were diarrhoea and metallic taste in ST and CT groups, respectively. A complete course of ST costs Indian Rupees (INR) 570.00, whereas CT costs INR 1080.00., Conclusion: H. pylori eradication rates, side effects, compliance, cost, and ulcer recurrences were similar between the two groups. The ST was more economical compared with CT.

Objectives: To compare triple therapy with sequential and concomitant therapies directly in a head-to-head comparison in Helicobacter pylori-infected patients., Design: Patients were allocated randomly as follows: a triple therapy with esomeprazole (20 mg), amoxicillin (1000 mg) and clarithromycin (500 mg) twice daily for 7 days; a sequential therapy with 5 days of esomeprazole (20 mg) and amoxicillin (1000 mg) twice daily, followed by 5 days of esomeprazole (20 mg), clarithromycin (500 mg) and metronidazole (400 mg) twice daily; or a concomitant therapy consisting of esomeprazole (20 mg), amoxicillin (1000 mg), clarithromycin (500 mg) and metronidazole (400 mg) twice daily for 7 days., Results: A total of 356 consecutive patients were included. The eradication rates for the triple, sequential and concomitant therapies were 83.6% [95% confidence interval (CI) 76.9-90.4%], 94.2% (95% CI 90.0-98.4%) and 91.7% (95% CI 86.7-96.6%), respectively, in the intention-to-treat population. The differences were significant only between triple and sequential therapies (P=0.01). The primary resistance rates to amoxicillin, clarithromycin and metronidazole were 0.6, 10.5 and 25.9%, respectively. Concomitant therapy was significantly better than triple therapy in cases with clarithromycin resistance (P=0.01)., Conclusion: Ten-day sequential therapy was significantly better than 7-day triple therapy in a clinical setting with low rates of clarithromycin and dual resistance. Concomitant therapy was significantly better than standard triple therapy in the subgroup of patients with clarithromycin-resistant strains.

Background: Recent reports have indicated that Helicobacter pylori (H. pylori) might have an effect on gastrointestinal flora; moreover, gastric commensual bacteria have been observed in the development of duodenal ulcer (DU)., Aims: In our study, we aimed to evaluate the effect of H. pylori eradication on gastrointestinal flora in DU patients., Methods: A case-control study was performed at Jiangsu Shengze Hospital between December, 2013 and April, 2014. The patients received antibiotic eradication therapy if H. pylori testing was positive. At least four weeks after cessation of the eradication therapy, a repeat gastroscopy was performed to collect biopsies again in the same position. Gastric mucosa samples and feces specimens were collected to extract bacteria DNA and then to quantify by real-time polymerase chain reaction (PCR)., Results: After the eradication of H. pylori, an increase of Lactobacillus group, Clostridium leptum subgroup, Enterobacteria and a decrease of Clostridium coccoides subgroup were found in the antrum. In the corpus, the number of bacteria in the Lactobacillus group was increased and the expression of Clostridium coccoides subgroup was significantly down-regulated. In the feces samples, only the number in the Lactobacillus group was increased. Moreover, the distribution was significantly different between female and the male patients., Conclusions: The presence of H. pylori in the stomach suppressed the colonization with Lactobacillus group, Clostridium leptum subgroup and Enterobacteria. Gender might affect the distribution and/or recolonization of the bacteria in DU patients.

Background: Peptic ulcer disease is the cause of dyspepsia in about 10% of people. Ninety-five percent of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H. pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain. This is an update of Ford AC, Delaney B, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive patients. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003840. DOI: 10.1002/14651858.CD003840.pub4., Objectives: To assess the proportion of peptic ulcers healed and the proportion of participants who remained free from relapse with eradication therapy against placebo or other pharmacological therapies in H. pylori-positive people.To assess the proportion of participants that achieved complete relief of symptoms and improvement in quality of life scores.To compare the incidence of adverse effects/drop-outs (total number for each drug) associated with the different treatments.To assess the proportion of participants in whom successful eradication was achieved., Search Methods: In this update, we identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (1950 to March 2016) and Ovid EMBASE (1980 to March 2016). To identify further relevant trials, we handsearched reference lists from trials selected by electronic searching, and published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology). The search was last updated in March 2016. We contacted members of Cochrane Upper GI and Pancreatic Diseases, and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials., Selection Criteria: We analysed randomised controlled trials of short- and long-term treatment of peptic ulcer disease in H. pylori-positive adults. Participants received at least one week of H. pylori eradication compared with ulcer healing drug, placebo or no treatment. Trials were included if they reported assessment from two weeks onwards., Data Collection and Analysis: We collected data on ulcer healing, recurrence, relief of symptoms and adverse effects. We calculated the risk ratio (RR) with 95% confidence intervals (CI) using both fixed-effect and random-effects models with Review Manager software (RevMan 5.3) based on intention-to-treat analysis as far as possible., Main Results: A total of 55 trials were included for one or more outcomes for this review.In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 participants, RR of ulcer persisting = 0.66, 95% confidence interval (CI) 0.58 to 0.76; 381/2286 (adjusted proportion: 12.4%) in eradication therapy plus UHD versus 304/1624 (18.7%) in UHD; low quality evidence) and no treatment (two trials, 207 participants, RR 0.37, 95% CI 0.26 to 0.53; 30/125 (adjusted proportion: 21.7%) in eradication therapy versus 48/82 (58.5%) in no treatment; low quality evidence).In gastric ulcer healing, the differences were imprecise between eradication therapy and UHD (15 trials, 1974 participants, RR 1.23, 95% CI 0.90 to 1.68; 220/1192 (adjusted proportion: 16.0%) in eradication therapy plus UHD versus 102/782 (13.0%) in UHD; very low quality evidence). In preventing duodenal ulcer recurrence the differences were imprecise between maintenance therapy with H.pylori eradication therapy and maintenance therapy with UHD (four trials, 319 participants, RR of ulcer recurring 0.73; 95% CI 0.42 to 1.25; 19/159 (adjusted proportion: 11.9%) in eradication therapy versus 26/160 (16.3%) in UHD; very low quality evidence), but eradication therapy was superior to no treatment (27 trials 2509 participants, RR 0.20, 95% CI 0.15 to 0.26; 215/1501 (adjusted proportion: 12.9%) in eradication therapy versus 649/1008 (64.4%) in no treatment; very low quality evidence).In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (12 trials, 1476 participants, RR 0.31, 95% CI 0.22 to 0.45; 116/697 (adjusted proportion: 16.3%) in eradication therapy versus 356/679 (52.4%) in no treatment; very low quality evidence). None of the trials reported proportion of people with gastric ulcer not healed after initial therapy between H.pylori eradication therapy and no active treatment or the proportion of people with recurrent gastric ulcer or peptic ulcers during maintenance therapy between H.pylori eradication therapy and ulcer healing drug therapy., Authors' Conclusions: Adding a one to two-week course of H. pylori eradication therapy is an effective treatment for people with H. pylori-positive duodenal ulcer when compared to ulcer healing drugs alone and no treatment. H. pylori eradication therapy is also effective in preventing recurrence of duodenal and gastric ulcer compared to no treatment. There is currently no evidence that H. pylori eradication therapy is an effective treatment in people with gastric ulcer or that it is effective in preventing recurrence of duodenal ulcer compared to ulcer healing drug. However, confidence intervals were wide and significant benefits or harms of H. pylori eradication therapy in acute ulcer healing of gastric ulcers compared to no treatment, and in preventing recurrence of duodenal ulcers compared to ulcer healing drugs cannot be ruled out.

Background: Marked epidemiological changes in upper gastrointestinal diseases and Helicobacter pylori infection have taken place in the Asian Pacific region. In particular, differences with respect to race in the multiracial Asian population in Malaysia have been important and interesting., Aim: A time trend study of upper gastrointestinal disease and H. pylori infection in three time periods: 1989-1990, 1999-2000 and 2009-2010 spanning a period of 20 years was carried out., Methods: Consecutive first time gastroscopies carried out on patients attending the University of Malaya Medical Center were studied. Diagnoses and H. pylori infection status were carefully recorded., Results: A steady decline in prevalence of duodenal ulcer (DU) and gastric ulcer (GU) from 21.1% to 9.5% to 5.0% and from 11.9% to 9.4% to 9.9% while an increase in erosive oesophagitis (EO) from 2.0% to 8.4% to 9.5% (chi-square for trend; P < 0.001) for the periods 1989-1990, 1999-200 and 2009-2010 were observed. The overall prevalence of H. pylori had also decreased from 51.7% to 30.3% to 11.1% for the same periods of time. The proportion of H. pylori positive ulcers had also decreased: DU (90.1%-69.8%-28.9%) and GU (86.6-56.8%-18.9%) (P < 0.001). This was observed in Malays, Chinese and Indians but the difference over time was most marked in Malays. There was a steady decline in the proportion of patients with gastric and oesophageal cancers., Conclusions: Peptic ulcers have declined significantly over a 20-year period together with a decline in H. pylori infection. In contrast, a steady increase in erosive oesophagitis was observed. Gastric and oesophageal squamous cell cancers have declined to low levels., (© 2016 John Wiley & Sons Ltd.)

Stomach cancer is one of the leading causes of cancer death worldwide, despite its incidence and mortality falling in many places. The discovery in 1984 that a bacterial infection with Helicobacter pylori could cause stomach and duodenal ulcers prompted work in its role in causing gastritis, and led to the first prospective study in 1991 by Forman et al., showing that infection with H.pylori increased the risk of stomach cancer in those infected by almost three-fold. Prior to then, it was hypothesized that stomach was caused by poor diets. While diets may still play a role, the falls in stomach cancer incidence have been associated with reductions in population prevalence of H. pylori. Discovery of the link was accelerated by the use of stored sera from other unrelated studies, and the use of serological assays. Since those discoveries the treatment landscape of gastric disorders has changed significantly, with a rapid uptake of antibiotic and proton pump inhibitors (triple) therapies in those who are H. pylori positive. Over time we have seen falls in gastric cancer, peptic and duodenal ulcers and in many of the procedures previously used to cure peptic ulcer disease, such as vagotomies and gastrectomies. Further still, an oral vaccine against H. pylori, first trialled in China, holds much promise of being the third vaccine against a cancer causing infection. If successful this would lead to a further reduction in H. pylori related conditions, and ultimately gastric cancer, an otherwise lethal disease., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Comparative assessment of results of detection of Helicobacter pylori (Hp) infection by breath tests with standard and locally produced 13С urea was done in 213 patients with gastric and duodenal pathology, including those who already were undergone the surgery. Invasive endoscopic biopsy test including rapid urease test (RUT), smear cytology and histology were also performed (tissue samples were obtained after endoscopy or surgery). RUT was carried out with the help of URE-HP test kit. Serological test for Hp antibodies was performed by IFA using kit ELISA. 13С urea breath test (UBT) was conducted for the determination of 13/12CO2 in breath samples by using of infrared spectroscope. In I group (125 patients) UBT was performed with standard 13С urea, in II group (88 patients) with locally produced 13С urea. Based on 5 different methods of Hp infection testing Hp positivity in 172 (80,8%) and Hp negativity in 41 (19,2%) patients were revealed. 13С-UBT showed the highest diagnostic value (accuracy-97,5%, sensibility-97,0%, specificity-100%) in Hp infection diagnosis. The (accuracy, sensibility and specificity of breath test with locally issued 13С urea (98,7%, 98,5% and 100% respectively) are the same as those for BT with standard 13С urea (96,7%, 96,2% and 100% respectively). These parameters are also highly credible in control of treatment efficiency (96,7%, 90,0% and 100% respectively). The correlation of index DOB‰ of breath test with results of RUT was revealed In Hp positive patients. This can serve as a marker of Hp infection rate. Preliminarily, in pre-clinical experimental study, harmless of locally issued 13С-urea from point of view of acute/sub-acute toxicity and allergy development was confirmed. The advantages (noninvasiveness, simplicity, rapidity, safety) and high diagnostic value of UBT (with both standard as well as locally produced 13С-urea) provide the opportunity to offer 13С-UBT as screening method of Hp infection diagnosis. It also should be recommended as a method of choice for controlling of Hp treatment efficiency. Taking into the consideration all above-mentioned we may recommend locally produced 13С-urea (Tbilisi, Georgia) for certification and further application.

In patients with gastric or duodenal ulcer associated with Helicobacter pylori, treatment of the infection improves healing and prevents complications and recurrences. The drug regimen generally consists of a high-dose proton-pump inhibitor (PPI) such as omeprazole plus antibiotics. Using the standard Prescrire methodology, we conducted a review of the literature in order to determine the standard empirical antibiotic regimen for H. pylori infection in adults with gastric or duodenal ulcer in France. In 2015, due to an increase in H. pylori resistance to clarithromycin, a 7-day course of the PPI + clarithromycin + amoxicillin combination is effective in only about 70% of cases. A Cochrane systematic review and meta-analysis of trials involving thousands of patients suggests that prolonging treatment with a PPI + amoxicillin + clarithromycin or a PPI + amoxicillin + metronidazole to 10 or 14 days improves the rate of H. pylori eradication by 5% to 10%. A metanalysis of seven trials including a total of about 1000 patients showed that combination therapy with a PPI + amoxicillin + clarithromycin + metronidazole for 5 days eradicates H. pylori in about 90% of cases, compared to about 80% of cases with a PPI + amoxicillin + clarithromycin given for 7 days. Sequential treatment with amoxicillin for 5 days, followed by clarithromycin + metronidazole for 5 days, has also been tested in thousands of patients. Efficacy and adverse effects were similar to those observed when the same antibiotics were taken simultaneously for 5 days. In randomised trials, replacing clarithromycin or amoxicillin with a fluoroquinolone yielded conflicting results. In 2009, nearly 20% of H. pylori isolates were resistant to levofloxacin in France. Tetracycline has only been evaluated in combination with bismuth. The few available data on doxycycline suggest that its efficacy is similar to that of tetracycline. A fixed-dose combination of bismuth subcitrate potassium + metronidazole + tetracycline is authorised in the European Union for use in combination with omeprazole for 10 days. It seems effective, even in case of clarithromycin resistance. However, bismuth can cause encephalopathy, and its value when added to antibiotics and a PPI is poorly documented. We found no robust comparative data on second-line empirical treatments. In patients with gastric or duodenal ulcer associated with H. pylori, eradication of the bacterium reduces the risk of complications and recurrence. In mid-2015, the choice of antibiotics is based on trials in which the primary endpoint was a negative urea breath test, which is an acceptable surrogate criterion. In previously untreated patients, the first-choice empirical treatment consists of three antibiotics: amoxicillin (2 g daily), clarithromycin (1 g daily) and metronidazole (1 g daily), plus a PPI (in practice, omeprazole 40 mg daily), with each drug taken in two divided doses per day. The antibiotics may be taken either simultaneously for five days, or sequentially (amoxicillin for 5 days, followed by clarithromycin + metronidazole for 5 days). The adverse effects of these antibiotic combinations correspond to those of their component drugs, which mainly consist of gastrointestinal disorders and the disulfiram-like reaction of metronidazole. Amoxicillin can be replaced by a fluoroquinolone in patients allergic to beta-lactam antibiotics, but there is a higher risk of resistance. Tetracycline and doxycycline appear effective, as few H. pylori strains are resistant in vitro. Bismuth can cause encephalopathy and should only be used in special cases.