Although most H. pylori infectors are asymptomatic, some may develop serious disease, such as gastric adenocarcinoma, gastric high-grade B cell lymphoma and peptic ulcer disease. Epidemiological and ...basic studies have provided evidence that infection with H. pylori carrying specific virulence factors can lead to more severe outcome. The virulence factors that are associated with gastric adenocarcinoma development include the presence, expression intensity and types of cytotoxin-associated gene A (CagA, especially EPIYA-D type and multiple copies of EPIYA-C) and type IV secretion system (CagL polymorphism) responsible for its translocation into the host cells, the genotypes of vacuolating cytotoxin A (vacA, s1/i1/m1 type), and expression intensity of blood group antigen binding adhesin (BabA, low-producer or chimeric with BabB). The presence of CagA is also related to gastric high-grade B cell lymphoma occurrence. Peptic ulcer disease is closely associated with cagA-genopositive, vacA s1/m1 genotype, babA2-genopositive (encodes BabA protein), presence of duodenal ulcer promoting gene cluster (dupA cluster) and induced by contact with epithelium gene A1 (iceA1), and expression status of outer inflammatory protein (OipA). The prevalence of these virulence factors is diverse among H. pylori isolated from different geographic areas and ethnic groups, which may explain the differences in disease incidences. For example, in East Asia where gastric cancer incidence is highest worldwide, almost all H. pylori isolates were cagA genopositive, vacA s1/i1/m1 and BabA-expressing. Therefore, selection of appropriate virulence markers and testing methods are important when using them to determine risk of diseases. This review summarizes the evidences of H. pylori virulence factors in relation with gastroduodenal diseases and discusses the geographic differences and appropriate methods of analyzing these virulence markers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Helicobacter pylori pathogenesis and disease outcomes are mediated by a complex interplay between bacterial virulence factors, host, and environmental factors. After H. pylori enters the host ...stomach, four steps are critical for bacteria to establish successful colonization, persistent infection, and disease pathogenesis: (1) Survival in the acidic stomach; (2) movement toward epithelium cells by flagella-mediated motility; (3) attachment to host cells by adhesins/receptors interaction; (4) causing tissue damage by toxin release. Over the past 20 years, the understanding of H. pylori pathogenesis has been improved by studies focusing on the host and bacterial factors through epidemiology researches and molecular mechanism investigations. These include studies identifying the roles of novel virulence factors and their association with different disease outcomes, especially the bacterial adhesins, cag pathogenicity island, and vacuolating cytotoxin. Recently, the development of large-scale screening methods, including proteomic, and transcriptomic tools, has been used to determine the complex gene regulatory networks in H. pylori. In addition, a more available complete genomic database of H. pylori strains isolated from patients with different gastrointestinal diseases worldwide is helpful to characterize this bacterium. This review highlights the key findings of H. pylori virulence factors reported over the past 20 years.
Background: The benefits of probiotics to the pediatric Helicobacter pylori infection remain uncertain. We tested whether the H. pylori‐infected children have an altered gut microflora, and whether ...probiotics‐containing yogurt can restore such change and improve their H. pylori‐related immune cascades.
Methods: We prospectively included 38 children with H. pylori infection confirmed by a positive 13C‐urea breath test (UBT) and 38 age‐ and sex‐matched noninfected controls. All of them have provided the serum and stool samples before and after 4‐week ingestion of probiotics‐containing yogurt. The serum samples were tested for the TNF‐α, IL‐10, IL‐6, immunoglobulin (Ig) A, G, E, pepsinogens I and II levels. The stool samples were tested for the colony counts of Bifidobacterium spp. and Escherichia coli. The follow‐up UBT indirectly assessed the H. pylori loads after yogurt usage.
Results: The H. pylori‐infected children had lower fecal Bifidobacterium spp. count (p = .009), Bifidobacterium spp./E. coli ratio (p = .04), serum IgA titer (p = .04), and pepsinogens I/II ratio (p < .001) than in controls. In the H. pylori‐infected children, 4‐week yogurt ingestion reduced the IL‐6 level (p < .01) and H. pylori loads (p = .046), but elevated the serum IgA and pepsinogen II levels (p < .001). Moreover, yogurt ingestion can improve the childhood fecal Bifidobacterium spp./E. coli ratio (p = .03).
Conclusions: The H. pylori‐infected children have a lower Bifidobacterium microflora in gut. The probiotics‐containing yogurt can offer benefits to restore Bifidobacterium spp./E. coli ratio in children and suppress the H. pylori load with increment of serum IgA but with reduction in IL‐6 in H. pylori‐infected children.
Background
Helicobacter pylori infection is the leading cause of peptic ulcer and chronic gastritis and may initiate gastric carcinogenesis following the Correa cascade. Another lineage of ...metaplasia, spasmolytic peptide‐expressing metaplasia (SPEM) has recently been found to be an alternative precursor to gastric cancer. To date, few reports have investigated gastric precancerous lesions among children with H. pylori infection. This study aimed to evaluate the histopathological pattern of H. pylori atrophic gastritis in children and the extent of precancerous lesions.
Materials and Methods
This study enrolled pediatric patients with H. pylori infection from 1998 to 2019. During esophagogastroduodenoscopy examinations, biopsy fragments were collected from the gastric antrum and corpus for rapid urease test, culture, and histology evaluation. The presence and degree of chronic inflammation, activity of gastritis, H. pylori density, atrophy, and intestinal metaplasia (IM) were assessed according to the modified Updated Sydney System. Trefoil factor 2 (TFF2) immunohistochemistry was also performed to assess SPEM in the gastric tissues collected from each case using rabbit anti‐human TFF2 antibodies.
Results
A total of 92 children with H. pylori infection and adequate gastric mucosa biopsies were enrolled. Esophagogastroduodenoscopy showed that 39 (42.4%) had duodenal ulcers, 11 (12.0%) had gastric ulcers, 41 (44.6%) had gastritis, and 1 (1.1%) had negative findings. Mild‐to‐moderate IM was identified in 4 patients (4.3%). SPEM was found in 8 patients (8.7%) with a significantly higher incidence among female patients (15.8% vs. 8.7%, p = .031). Gastric glandular atrophy presented in 28 patients (30.4%), and high‐grade atrophy was more common in female patients (3.2% vs. 1.9%, p = .031).
Conclusions
The prevalence rates of atrophic gastritis in the children with H. pylori infection were 30.4% for gastric glandular atrophy, 4.3% for IM and 8.7% for SPEM. SPEM and high‐grade atrophy were more common in female patients.
To establish the non-inferior efficacy of vonoprazan versus lansoprazole in the treatment of Asian patients with erosive oesophagitis (EO).
In this phase III, double-blind, multicentre study, ...patients with endoscopically confirmed EO were randomised 1:1 to receive vonoprazan 20 mg or lansoprazole 30 mg, once daily for up to 8 weeks. The primary endpoint was EO healing rate at 8 weeks. The secondary endpoints were EO healing rates at 2 and 4 weeks. Safety endpoints included treatment-emergent adverse events (TEAEs).
In the vonoprazan (n=238) and lansoprazole (n=230) arms, 8-week EO healing rates were 92.4% and 91.3%, respectively (difference 1.1% (95% CI -3.822% to 6.087%)). The respective 2-week EO healing rates were 75.0% and 67.8% (difference 7.2% (95% CI -1.054% to 15.371%)), and the respective 4-week EO healing rates were 85.3% and 83.5% (difference 1.8% (95% CI -4.763% to 8.395%)). In patients with baseline Los Angeles classification grade C/D, 2-week, 4-week and 8-week EO healing rates were higher with vonoprazan versus lansoprazole (2 weeks: 62.2% vs 51.5%, difference 10.6% (95% CI -5.708% to 27.002%); 4 weeks: 73.3% vs 67.2%, difference 6.2% (95% CI -8.884 to 21.223); and 8 weeks: 84.0% vs 80.6%, difference 3.4% (95% CI -9.187% to 15.993%)). Overall, EO healing rates appeared higher with vonoprazan versus lansoprazole. TEAE rates were 38.1% and 36.6% in the vonoprazan and lansoprazole group, respectively.
Our findings demonstrate the non-inferior efficacy of vonoprazan versus lansoprazole in terms of EO healing rate at 8 weeks in this population. Safety outcomes were similar in the two treatment arms.
NCT02388724.
Summary Background Whether concomitant therapy is superior to bismuth quadruple therapy or 14-day triple therapy for the first-line treatment of Helicobacter pylori infection remains poorly ...understood. We aimed to compare the efficacy and safety of 10-day concomitant therapy, 10-day bismuth quadruple therapy, and 14-day triple therapy in the first-line treatment of H pylori. Methods In this multicentre, open-label, randomised trial, we recruited adult patients (aged >20 years) with H pylori infection from nine medical centres in Taiwan. Patients who had at least two positive tests from the rapid urease test, histology, culture, or serology or who had a single positive13 C-urea breath test for gastric cancer screening were eligible for enrolment. Patients were randomly assigned (1:1:1) to either concomitant therapy (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily) for 10 days; bismuth quadruple therapy (bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day) for 10 days; or triple therapy (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily) for 14 days. A computer-generated permuted block randomisation sequence with a block size of 6 was used for randomisation, and the sequence was concealed in an opaque envelope until the intervention was assigned. Investigators were masked to treatment allocation. The primary outcome was the eradication frequency of H pylori with first-line therapy assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov , number NCT01906879. Findings Between July 17, 2013, and April 20, 2016, 5454 patients were screened for eligibility. Of these, 1620 patients were randomly assigned in this study. The eradication frequencies were 90·4% (488/540 95% CI 87·6–92·6) for 10-day bismuth quadruple therapy, 85·9% (464/540 82·7–88·6) for 10-day concomitant therapy, and 83·7% (452/540 80·4–86·6) for 14-day triple therapy in the intention-to-treat analysis. 10-day bismuth quadruple therapy was superior to 14-day triple therapy (difference 6·7% 95% CI 2·7–10·7, p=0·001), but not 10-day concomitant therapy. 10-day concomitant therapy was not superior to 14-day triple therapy. The frequency of adverse events was 67% (358/533) in patients treated with 10-day bismuth quadruple therapy, 58% (309/535) in patients treated with 10-day concomitant therapy, and 47% (252/535) in patients treated with 14-day triple therapy. Interpretation Bismuth quadruple therapy is preferable to 14-day triple therapy in the first-line treatment in the face of rising prevalence of clarithromycin resistance. Concomitant therapy given for 10 days might not be optimum and a longer treatment length should be considered. Funding National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.
Background
The eradication rates of sequential therapy are high in clinical trials; however, the adherence for follow‐up or the patient population in a real‐world setting might be different from ...those in trails. This study investigates the effectiveness of sequential therapy in a real‐world setting and the factors that lead to treatment failure.
Materials and Methods
In this retrospective study, patients receiving sequential therapy as a first‐line anti‐Helicobacter pylori (H. pylori) treatment in a real‐world setting were reviewed. The age adjusted Charlson Comorbidity Index (age‐CCI) and baseline variety of medications were reviewed to determine factors correlated with nonadherence for post‐treatment testing and H. pylori eradication failure.
Results
A total of 1053 patients were reviewed. A total of 579 patients receiving sequential therapy were included in the analyses. Among them, 462 received post‐treatment testing and were placed into the follow‐up group. Thus, the post‐treatment testing rate was 79.8%. Stroke was an independent factor of nonadherence for post‐treatment testing. In the follow‐up group, the eradication failure rate was 8.2%. Female sex (odds ratio OR 2.41 95% CI 1.16–5.03, p = 0.02) and age‐CCI ≥2 (OR 3.16 1.05–9.48, p = 0.04) were independent factors of H. pylori eradication failure. The eradication failure rates were 14.4%, 7.8%, 7.1%, and 3.1% for the females with age‐CCI ≥2, females with age‐CCI <2, males with age‐CCI ≥2, and males with age‐CCI <2 subgroups, respectively (p = 0.027).
Conclusions
In a real‐world setting, the adherence rate of post‐treatment testing for sequential therapy as a first‐line anti‐H. pylori treatment was found to be suboptimal. Female sex and age‐CCI ≥2 were independent factors of eradication failure.
Background
Previous international consensus statements provided general policies for the management of Helicobacter pylori infection. However, there are geographic differences in the prevalence and ...antimicrobial resistance of H. pylori, and in the availability of medications and endoscopy. Thus, nationwide or regional consensus statements are needed to improve control of H. pylori infection and gastric cancer.
Materials and Methods
This consensus statement for management of H. pylori in Taiwan has three major sections: (1) optimal diagnosis and indications; (2) current treatment strategies; and (3) screening‐to‐treat and surveillance for control of gastric cancer. The literature review emphasized recent data for development of draft statements and determination of levels of evidence. Twenty‐five Taiwan experts conducted a consensus conference, by a modified Delphi process, to modify the draft statements. Consensus, defined as an agreement of least 80% of the experts, and recommendation grade were determined by anonymous voting.
Results
There were 24 consensus statements. Section 1 has seven statements on recommendations for the diagnosis and indications for treatment of H. pylori infection. Section 2 has 10 statements that provide an updated treatment algorithm for first‐line, second‐line, and third‐line regimens. Section 3 has seven statements regarding H. pylori eradication for reducing the risk of gastric cancer, with a cost‐benefit analysis. After H. pylori eradication, the consensus highlights the use of endoscopic surveillance and/or chemoprevention to further reduce the burden of gastric cancer.
Conclusions
This consensus statement has updated recommendations for improving the clinical management of H. pylori infection in areas such as Taiwan, which have high prevalence of H. pylori infection and gastric cancer.
Since the publication of the Asia-Pacific consensus on gastro-oesophageal reflux disease in 2008, there has been further scientific advancement in this field. This updated consensus focuses on proton ...pump inhibitor-refractory reflux disease and Barrett's oesophagus.
A steering committee identified three areas to address: (1) burden of disease and diagnosis of reflux disease; (2) proton pump inhibitor-refractory reflux disease; (3) Barrett's oesophagus. Three working groups formulated draft statements with supporting evidence. Discussions were done via email before a final face-to-face discussion. We used a Delphi consensus process, with a 70% agreement threshold, using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to categorise the quality of evidence and strength of recommendations.
A total of 32 statements were proposed and 31 were accepted by consensus. A rise in the prevalence rates of gastro-oesophageal reflux disease in Asia was noted, with the majority being non-erosive reflux disease. Overweight and obesity contributed to the rise. Proton pump inhibitor-refractory reflux disease was recognised to be common. A distinction was made between refractory symptoms and refractory reflux disease, with clarification of the roles of endoscopy and functional testing summarised in two algorithms. The definition of Barrett's oesophagus was revised such that a minimum length of 1 cm was required and the presence of intestinal metaplasia no longer necessary. We recommended the use of standardised endoscopic reporting and advocated endoscopic therapy for confirmed dysplasia and early cancer.
These guidelines standardise the management of patients with refractory gastro-oesophageal reflux disease and Barrett's oesophagus in the Asia-Pacific region.
The transcriptional network of the SRY (sex determining region Y)‐box 17 (SOX17) and the prognostic impact of SOX17 protein expression in human cancers remain largely unclear. In this study, we ...evaluated the prognostic effect of low SOX17 protein expression and its dysregulation of transcriptional network in esophageal squamous cell carcinoma (ESCC). Low SOX17 protein expression was found in 47.4% (73 of 154) of ESCC patients with predicted poor prognosis. Re‐expression of SOX17 in ESCC cells caused reduced foci formation, cell motility, decreased ESCC xenograft growth and metastasis in animals. Knockdown of SOX17 increased foci formation in ESCC and normal esophageal cells. Notably, 489 significantly differential genes involved in cell growth and motility controls were identified by expression array upon SOX17 overexpression and 47 genes contained putative SRY element in their promoters. Using quantitative chromatin immunoprecipitation‐PCR and promoter activity assays, we confirmed that MACC1, MALAT1, NBN, NFAT5, CSNK1A1, FN1 and SERBP1 genes were suppressed by SOX17 via the SRY binding‐mediated transcriptional regulation. Overexpression of FN1 and MACC1 abolished SOX17‐mediated migration and invasion suppression. The inverse correlation between SOX17 and FN1 protein expression in ESCC clinical samples further strengthened our conclusion that FN1 is a transcriptional repression target gene of SOX17. This study provides compelling clinical evidence that low SOX17 protein expression is a prognostic biomarker and novel cell and animal data of SOX17‐mediated suppression of ESCC metastasis. We establish the first transcriptional network and identify new suppressive downstream genes of SOX17 which can be potential therapeutic targets for ESCC.
What's new?
While the SOX17 gene is known to encode a transcription factor important for esophagus tissue development, the transcriptional network of SOX17 and the prognostic impact of SOX17 protein expression in human cancers both remain largely unclear. Here, the authors discovered the first transcriptional network of SOX17 in cancer and verified the novel transcriptional repression target genes of SOX17 involved in migration and invasion of esophageal cancer. They provided evidence for metastasis suppression by SOX17 in an animal model and identified low SOX17 expression as a prognosis marker in esophageal cancer patients, indicating SOX17 as a potential target for therapeutic intervention.
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