Relationship between the iceA gene of Helicobacter pylori and clinical outcomes.

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

Helicobacter pylori infection causes gastric inflammation and gastritis which increase the risk for peptic ulcer disease (PUD) and gastric cancer. It is estimated that more than half of the world's population is infected with H. pylori. The etiologic factors contributing to clinical outcome include environmental factors, genetic factors of host and virulence factors of H. pylori. Several genes of H. pylori play a key role in pathogenesis such as cagA, vacA and iceA genes. The predominant H. pylori strains circulating among geographic locations differ in regard to genomic structure. The prevalence of more pathogenic bacterial genotype in certain areas may have important epidemiological consequences and be associated with the severity of H. pylori-related diseases in such regions. In addition, previous studies demonstrated that the relationship between virulence genes of H. pylori and clinical outcome is still controversial and varies between each ethnic group. Because of this diversity of reports associating the virulence genes with the clinical outcome from different geographic regions, it is important to analyze the association between genes cagA, vacA and iceA of H. pylori and clinical outcome in Thai setting. The aim of this study was to examine the prevalence of genes cagA, vacA and iceA of H. pylori in patients with PUD compared with patients with non-ulcer dyspepsia (NUD) and to determine the association of these genes with PUD. In this study, 40 H. pylori isolates were obtained from PUD patients and 40 isolates from NUD patients. Genes cagA, vacA and iceA of H. pylori were identified by using polymerase chain reaction (PCR) with specific primers. The result of this study demonstrated that cagA positive, vacA si, m2 and iceA2 genotypes were found predominantly in H. pylori in Thailand .The presence of either cagA, allelic variant vacA and iceA alone does not have a predictive value as a risk marker for clinical outcome of H. pylori infection. In addition, high prevalence of mixed iceA isolates (48.75%) was found in Thai patients. All of these isolates contained single vacA genotype which suggests the presence of mixed iceA genotype in one strain. From analysis, vacA sla, mixed iceA genotype was found to be significantly associated with PUD (P=0.04, OR=2.51, 95%CI=1.05-6.04). Therefore, vac A sla, mixed iceA genotype may be regarded as marker for predicting the peptic ulcer disease in Thai setting if the mixed iceA genotype has been proven to be really existed.

BackgroundThe most prevalent stomach infection in the world is caused by Helicobacter pylori (H. pylori). Several pathogenicity genes, including cagA, vacA, babA2, dupA, iceA, and oipA, are associated with an increased risk of gastrointestinal disease such as peptic ulcer and stomach cancer. This research aims to determine the prevalence of different H. pylori genotypes and correlate their risk in the development of gastrointestinal diseases in the Ecuadorian population.MethodsA cross-sectional research of 225 patients at the Calderón Hospital in Quito, Ecuador, was conducted. End point PCRs were run to determine the presence of 16S rRNA, cagA, vacA (m1), vacA (s1), babA2, dupA, iceA1, and oipA virulence genes. Chi-square test, odds ratios (OR) and 95% confidence intervals (CI) were utilized for the statistical analysis.ResultsH. pylori infection was present in 62.7% of people. Peptic ulcers were seen in 22.2% and malignant lesions in 3.6% of patients. Genes oipA (93.6%), vacA (s1) (70.9%), and babA2 (70.2%) were the most prevalent. cagA/vacA (s1m1) and cagA/oipA (s1m1) combinations were found in 31.2% and 22.7% of the cases, respectively. Acute inflammation has a significant correlation with the genes cagA (OR = 4.96 95% CI: 1.1–22.41), babA2 (OR = 2.78 95% CI: 1.06–7.3), and the cagA/oipA combination (OR = 4.78, 95% CI: 1.06–21.62). Follicular hyperplasia was associated with iceA1 (OR = 3.13; 95% CI: 1.2–8.16), babA2 (OR = 2.56; 95% CI: 1.14–5.77), cagA (OR = 2.19; 95% CI: 1.06–4.52), and the cagA/oipA combination (OR = 2.32, 95% CI: 1.12–4.84). The vacA (m1) and vacA (s1m1) genes were associated with gastric intestinal metaplasia (OR = 2.71 95% CI: 1.17–6.29) (OR = 2.33 95% CI: 1.03–5.24). Finally, we showed that cagA/vacA (s1m1) gene combination increased the risk of duodenal ulcer development (OR = 2.89, 95% CI 1.10–7.58).ConclusionThis study makes a significant contribution by offering genotypic information regarding H. pylori infection. The presence of several H. pylori genes was associated with the onset of gastrointestinal illness in the Ecuadorian population.

Purpose: Helicobacter pylori (H. pylori) infection causes gastric inflammation and gastritis which increase the risk for peptic ulcer disease (PUD). Several genes of H. pylori such as cagA, vacA and iceA genes may play an important role in pathogenesis of this disease. The aim of this study was to examine the prevalence of genes cagA, vacA and iceA of H. pylori in patients with PUD compared with patients with non-ulcer dyspepsia (NUD) and to determine the association of these genes with PUD. Methods: In this study, 40 H. pylori isolates were obtained from PUD patients and 40 isolates from NUD patients. Genes cagA, vacA and iceA of H. pylori were identified by using polymerase chain reaction (PCR) with specific primers. Results: The result of this study demonstrated that cagA positive, vacA s1, m2 and iceA2 genes were found predominantly in H. pylori in Thailand. The presence of either cagA, allelic variant vacA and iceA alone does not have a predictive value as a risk marker for clinical outcome of H. pylori infection. In addition, high prevalence of mixed iceA isolates (48.75%) was found in Thai patients. All of these isolates contained single vacA genotype which suggests the presence of mixed iceA genotype in one strain. From analysis, vacA s1a, mixed iceA genotype was found to be significantly associated with PUD (P = 0.04, OR = 2.51, 95%CI = 1.05–6.04). Conclusions: Genes vacA s1a and mixed iceA genotype may play important roles in the pathogenesis of peptic ulcer disease and might be regarded as marker for predicting peptic ulcer disease in Thailand.

To evaluate the accuracy of several methods aimed to detect Helicobacter pylori stool antigens in patients with upper gastrointestinal bleeding. Thirty-four patients with upper gastrointestinal bleeding because of peptic ulcer were included. The first stool sample during hospitalization was collected, and stool antigens were determined with: polyclonal enzyme-linked immunosorbent assay (Premier-Platinum-HpSA); monoclonal enzyme-linked immunosorbent assay (Amplified-IDEIA-HpStAR); and rapid monoclonal immunochromatographic test (ImmunoCard-STAT HpSA). A patient was considered infected when H. pylori was diagnosed with invasive tests (rapid urease test or histology) or with (13)C-urea breath test. When all tests were negative, a new breath test was repeated after stopping proton pump inhibitors. All patients were infected and, therefore, only sensitivity of the tests could be calculated: polyclonal enzyme-linked immunosorbent assay (74%), monoclonal enzyme-linked immunosorbent assay (94%), and rapid monoclonal immunochromatographic test (60%; concordance between the two observers was high, kappa = 0.9). Neither the presence of maelena nor the delay in obtaining stool samples explained false negatives. Neither the polyclonal enzyme-linked immunosorbent assay stool antigen test nor the rapid immunochromatographic stool antigen test can be recommended to diagnose H. pylori infection in patients with upper gastrointestinal bleeding. However, the monoclonal enzyme-linked immunosorbent assay stool antigen test is highly sensitive for detecting the infection in patients with this complication, although more studies are necessary to evaluate the specificity of the method.

Family history of peptic ulcer and infection with Helicobacter pylori have been identified as major risk factors for peptic ulcer disease. It is unclear, however, to what degree their impacts are independent of each other. This question was addressed in a cross-sectional study among 299 consecutive out-patients (25-54 years old) of a general practitioner. Adjusted odds ratios (95% confidence intervals) for gastroscopically verified peptic ulcer disease were 3.8 (1.4-10.1) for persons with H. pylori infection, 8.4 (2.9-24.1) for persons with a family history of ulcer, and 29.5 (6.1-143.9) for persons with both risk factors compared with persons without these risk factors. These results suggest strong, multiplicative contributions of both factors to the risk for peptic ulcer disease.

The association between Helicobacter pylori (HP) infection and colorectal neoplasm risk was not clear. The aim of this study was to evaluate whether HP infection can increase the risk of developing colorectal neoplasm by meta-analysis. A detailed literature search was performed on Medline, PubMed, Web of Science, and China National Knowledge Infrastructure for related research publications written in English and/or Chinese. The relevant case-control or cohort studies reporting an association between HP infection and colorectal neoplasm risk were screened and included in this meta-analysis. The association between HP infection and colorectal neoplasm risk was expressed by odds ratio (OR) and its 95% confidence interval (CI). The heterogeneity among the included articles was assessed by I 2 test, and the pooled OR was calculated by fixed effect model in case of no significant heterogeneity otherwise random effect model was employed. All the statistical analyses were done by STATA-11.0 and MetaAnalyst Beta 3.13 software. Finally, a total of 2081 colorectal neoplasm patients and 5598 healthy controls from nine eligible studies were included in this meta-analysis. The pooled OR for the association between HP infection and colorectal neoplasm risk was 0.18 with its 95% CI of 0.99-1.40, (P > 0.05). We further divided the colorectal neoplasm into the hyperplastic polyps, adenomas and colorectal cancer sub-groups according to colorectal neoplasm types. The pooled ORs and their 95% CIs were OR Hyperplastic_polyps = 0.72, 95% CI: 0.44-1.18, (P > 0.05), OR Adenomas = 1.83, 95% CI: 1.35-2.51, (P < 0.01), OR Colorectal_cancer = 1.08, 95% CI: 0.89-1.68 (P > 0.05). For different region sub-groups, the pooled ORs and 95% CIs were OR South_Korea = 1.18, 95% CI: 0.84-1.66, (P > 0.05), OR China = 0.78, 95% CI: 0.53-1.13, (P > 0.05), OR Taiwan = 1.06, 95% CI: 0.69-1.62, (P > 0.05), OR Japan = 1.33, 95% CI: 1.07-1.65, (P < 0.05) for South Korea, China main land, Taiwan and Japanese. In general, no statistical association between HP infection and colorectal neoplasm risk was found in this meta-analysis. But, HP infection may increase the risk of developing colorectal adenomas.

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.

Relationship Between the Helicobacter pylori Icea Gene and Clinical Outcomes in Western Countries: Meta-Analysis

A Functional Polymorphism of Toll-Like Receptor 4 Gene Increases Risk of Gastric Carcinoma and Its Precursors

Background: Non-steroidal anti-inflammatory drug and aspirin (here collectively called NSAIDs) use is the second most common aetiologic factor for peptic ulcer disease and a major factor for peptic ulcer complications. The role of NSAIDs in the pathogenesis of uncomplicated peptic ulcer is less well understood and the interaction between NSAIDs and Helicobacter pylori infection on ulcer development is controversial. The aim of the present study was to examine the role of NSAIDs in the occurrence and clinical features of uncomplicated peptic ulcer disease. Methods: A total of 1091 consecutive patients referred for open-access upper gastrointestinal endoscopy by general practitioners (GPs) were enrolled. The use of NSAIDs was gathered from a structured questionnaire completed by the patients and from patient files by GPs. The exclusion criteria were previous H. pylori eradication and gastric surgery, as well as symptoms and/or signs suggestive of acute gastrointestinal bleeding. Results: Of the whole study group (n = 1091), 76 (7%) patients had a peptic ulcer. Thirty patients had an NSAID-use-associated peptic ulcer and 46 patients a non-NSAID-use peptic ulcer. Of patients with chronic gastritis (n = 599), 71% were H. pylori-positive and 108 used NSAIDs. Of those with chronic gastritis, 23 had an NSAID-use-associated peptic ulcer and 38 a non-NSAID ulcer. Of patients with normal gastric histology (n = 492), 75 patients used NSAIDs, 7 had an NSAID ulcer and 8 a non-NSAID ulcer. The only independent risk factor for peptic ulcer in patients using NSAIDs was H. pylori infection (odds ratio (OR) 3.1, 95% confidence interval (CI) 1.3-7.3), whereas dyspepsia (OR 1.0, 95% CI 0.4-2.4), male sex (OR 1.4, 95% CI 0.6-3.4), age (OR 1.0 per decade, 95% CI 0.8-1.3) and anaemia (OR 2.9, 95% CI 0.9-8.7) were not risk factors. In patients not using NSAIDs, independent risk factors for peptic ulcer were dyspepsia (OR 4.3, 95% CI 2.1-8.8), male sex (OR 2.0, 95% CI 1.1-2.8), age (OR 1.2 per decade, 95% CI 1.0-1.5), anaemia (OR 6.2, 95% CI 2.6-14.9) and H. pylori infection (OR 7.5, 95% CI 3.4-16.6). When comparing patients using NSAIDs or not, the OR of patients on NSAIDs for peptic ulcer was 2.7 (95% CI 1.5-5.0) among patients with chronic H. pylori gastritis (n = 424) and 5.3 (95% CI 1.8-15.0) among patients with normal gastric mucosa (n = 492). Conclusions: The use of NSAIDs increases the risk of peptic ulcer 3- and 5-fold in H. pylori-positive and H. pylori-negative patients, respectively. Dyspepsia is a poor predictor of peptic ulcer among patients using NSAIDs, and serologic H. pylori testing and treatment for chronic NSAID users is recommended.

Non-steroidal anti-inflammatory drug and aspirin (here collectively called NSAIDs) use is the second most common aetiologic factor for peptic ulcer disease and a major factor for peptic ulcer complications. The role of NSAIDs in the pathogenesis of uncomplicated peptic ulcer is less well understood and the interaction between NSAIDs and Helicobacter pylori infection on ulcer development is controversial. The aim of the present study was to examine the role of NSAIDs in the occurrence and clinical features of uncomplicated peptic ulcer disease. A total of 1091 consecutive patients referred for open-access upper gastrointestinal endoscopy by general practitioners (GPs) were enrolled. The use of NSAIDs was gathered from a structured questionnaire completed by the patients and from patient files by GPs. The exclusion criteria were previous H. pylori eradication and gastric surgery, as well as symptoms and/or signs suggestive of acute gastrointestinal bleeding. Of the whole study group (n = 1091), 76 (7%) patients had a peptic ulcer. Thirty patients had an NSAID-use-associated peptic ulcer and 46 patients a non-NSAID-use peptic ulcer. Of patients with chronic gastritis (n = 599), 71% were H. pylori-positive and 108 used NSAIDs. Of those with chronic gastritis, 23 had an NSAID-use-associated peptic ulcer and 38 a non-NSAID ulcer. Of patients with normal gastric histology (n = 492), 75 patients used NSAIDs, 7 had an NSAID ulcer and 8 a non-NSAID ulcer. The only independent risk factor for peptic ulcer in patients using NSAIDs was H. pylori infection (odds ratio (OR) 3.1, 95% confidence interval (CI) 1.3-7.3), whereas dyspepsia (OR 1.0, 95% CI 0.4-2.4), male sex (OR 1.4, 95% CI 0.6-3.4), age (OR 1.0 per decade, 95% CI 0.8-1.3) and anaemia (OR 2.9, 95% CI 0.9-8.7) were not risk factors. In patients not using NSAIDs, independent risk factors for peptic ulcer were dyspepsia (OR 4.3, 95% CI 2.1-8.8), male sex (OR 2.0, 95% CI 1.1-2.8), age (OR 1.2 per decade, 95% CI 1.0-1.5), anaemia (OR 6.2, 95% CI 2.6-14.9) and H. pylori infection (OR 7.5, 95% CI 3.4-16.6). When comparing patients using NSAIDs or not, the OR of patients on NSAIDs for peptic ulcer was 2.7 (95% CI 1.5-5.0) among patients with chronic H. pylori gastritis (n = 424) and 5.3 (95% CI 1.8-15.0) among patients with normal gastric mucosa (n = 492). The use of NSAIDs increases the risk of peptic ulcer 3- and 5-fold in H. pylori-positive and H. pylori-negative patients, respectively. Dyspepsia is a poor predictor of peptic ulcer among patients using NSAIDs, and serologic H. pylori testing and treatment for chronic NSAID users is recommended.

Risks of substance uses, alcohol flush response, Helicobacter pylori infection and upper digestive tract diseases—An endoscopy cross‐sectional study

Association between interleukin-8 gene −251 T/A polymorphism and the risk of peptic ulcer disease: A meta-analysis

The Prevalence of Idiopathic Peptic Ulcer and Changing Trend of Peptic Ulcer Disease and Helicobacter Pylori Infection Between 10 Years in Korea