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Javanbakhat P, Peeridogaheh H, Nemati R, Yazdanbod A, Teimourpour A, Sadeghnezhad M, Esmaelizad M, Teimourpour R. Exploring virulence factors of Helicobacter pylori isolated from gastric biopsy. Mol Biol Rep 2024; 51:192. [PMID: 38270789 DOI: 10.1007/s11033-023-09075-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 10/13/2023] [Indexed: 01/26/2024]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) colonizes human gastric mucosa and is classified as class one carcinogenic bacteria. In this regard, this study aimed to detect major virulence factors in H. pylori strains recovered from gastric biopsy in patients referred to Aras Clinique in Ardabil, northwest of Iran (2019-2021). MATERIALS AND METHODS In this descriptive-cross sectional study, 287 dyspeptic patients were included. For bacterial isolation, gastric biopsy specimens (n=287) were taken from gastric antrum, then aseptically were cultured on the selective medium and incubated at 37C in microaerophilic conditions for 3-5 days. RESULTS 25.18% of all (n = 70) patients were found to be infected with H. pylori upon endoscopy. Of them, 9 patients (12.857%) and 2 patients (2.875%) had peptic ulcer disease and gastric cancer respectively. According to the different patterns of virulence factors, 57 virutypes were identified in which oipA-vacAs1-vacAm2 (3, 4.28% n =) and oipA-vacAs1-vacAs2-vacAm2 (3, 4.28% n =) were the most common patterns. The simultaneous presence of vacAS2, vacAm2 and hopQ2 genes was observed in both patients with gastric cancer. OipA (n = 562.5%), VacAs1 (n = 6.75%), VacAs2 (n = 6.75%), and VacAm2 (n = 787.5%) were found to be the most prevalent virulence factor. CONCLUSION According previous studies, it is confirmed that the cagPAI gene cluster and vacA gene alleles are strongly correlated with gastritis and gastrointestinal tract adenocarcinomas. Our study indicated that 50% of the indigenous strains of H. pylori harbor these oncogenic genes and they are hypervirulent.
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Affiliation(s)
- Parisa Javanbakhat
- Department of Microbiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Hadi Peeridogaheh
- Department of Microbiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
- Digestive Diseases Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
| | - Rasool Nemati
- Departments of Internal Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Abbas Yazdanbod
- Departments of Internal Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
- Digestive Diseases Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Amir Teimourpour
- Blood Transfusion Research Center, High Institute for Research and Education, Tehran, Iran
| | - Mahin Sadeghnezhad
- Department of Microbiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Majid Esmaelizad
- Central Lab, Razi Vaccine and Serum Research Institute, Karaj, Iran
| | - Roghayeh Teimourpour
- Department of Microbiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
- Zoonoses Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
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Hassuna NA, Hussien SS, Abdelhakeem M, Aboalela A, Ahmed E, Abdelrahim SS. Regulatory B cells (Bregs) in Helicobacter pylori chronic infection. Helicobacter 2023; 28:e12951. [PMID: 36661205 DOI: 10.1111/hel.12951] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 01/01/2023] [Accepted: 01/04/2023] [Indexed: 01/21/2023]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection is linked with a wide variety of diseases and was reported in more than half of the world's population. Chronic H. pylori infection and its final clinical outcome depend mainly on the bacterial virulence factors and its ability to manipulate and adapt to human immune responses. Bregs blood levels have been correlated with increased bacterial load and infection chronicity, especially Gram-negative bacterial infection. This study aimed to identify prevalence and virulence factors of chronic H. pylori infection among symptomatic Egyptian patients and to examine its possible correlation to levels of regulatory B cells (Bregs) in blood. MATERIALS AND METHODS Gastric biopsies and blood samples from each of 113 adult patients, who underwent upper endoscopy, were examined for the detection of H. pylori by culture and PCR methods. Conventional PCR was used to determine various virulent genes prevalence and association to clinical outcome. Flow cytometry was used to evaluate Bregs levels. RESULTS Helicobacter pylori prevalence was 49.1% (55/112). Regarding virulence genes incidence, flaA gene was detected in 73% (40/55), vir B11 in 56.4% (31/55), hopZ1 in 34.5% (19/55), hopZ2 in 89% (49/55), babA2 in 52.7% (29/55), dupA jhp917 in 61.8% (34/55), vacA m1/m2 in 70.9% (39/55), and vacA s1/s2 in 69% (38/55) strains. Bregs levels were significantly lower in H. pylori-infected patients (p = 0.013), while total leukocyte count (TLC) showed no significant differences. CONCLUSION Helicobacter pylori infection prevalence was almost 49%, and the infection was found to be related to inflammatory conditions as gastritis and ulcers rather than malignant transformations. Also, we found that CD24+ CD38+ B cells were downregulated in H. pylori-infected patients.
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Affiliation(s)
- Noha A Hassuna
- Medical Microbiology and Immunology Department, Faculty of Medicine, Minia University, Minia, Egypt
| | - Sahar Sh Hussien
- Medical Microbiology and Immunology Department, Faculty of Medicine, Minia University, Minia, Egypt
| | - Mohammed Abdelhakeem
- Clinical Pathology Department, Faculty of Medicine, Minia University, Minia, Egypt
| | | | - Elham Ahmed
- Internal Medicine Department, Faculty of Medicine, Minia University, Minia, Egypt
| | - Soha S Abdelrahim
- Medical Microbiology and Immunology Department, Faculty of Medicine, Minia University, Minia, Egypt
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Lee JY. Triple Therapy. HELICOBACTER PYLORI 2023:541-552. [DOI: 10.1007/978-981-97-0013-4_44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Prevalence of Helicobacter pylori Virulence Genes and Their Association with Chronic Gastritis in Beijing, China. Curr Microbiol 2022; 80:33. [PMID: 36482124 DOI: 10.1007/s00284-022-03135-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 11/28/2022] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori is closely related to chronic gastritis. The aim of the study was to investigate the correlation between H. pylori virulence genes and chronic gastritis in order to determine the pathogenic role of H. pylori virulence genes in chronic gastritis. Gastric mucosal tissues were obtained from 142 patients with chronic gastritis at three Beijing hospitals. The presence of virulence genes was determined by polymerase chain reaction (PCR) from H. pylori DNA. Multilocus sequence typing (MLST) and a phylogenetic tree were performed to characterize the overall genetic diversity. 91 new sequence types were identified by MLST in this study, and all strains showed high genetic diversity. The H. pylori isolates were divided into three types: hspEAsia strains (61 strains), hpEurope strains (15 strains), and mixed strains (16 strains). Some virulence genes were found to be significantly different between strains. The highest positive rates were found for dupA in chronic atrophic gastritis (AG), iceA1 in chronic non-atrophic gastritis with erosions, and iceA2 in chronic non-atrophic gastritis. The presence of dupA was found to be inversely related to the risk of AG. The H. pylori strains display high genetic diversity. Some virulence genes were found to be significantly different between diseases. The detection of various virulence genes is critical for screening high-risk populations for precancerous lesions and for the early prevention and control of gastric cancer.
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Ang D, Koo SH, Chan YH, Tan TY, Soon GH, Tan CK, Lin KW, Krishnasamy-Balasubramanian JK, Wong YJ, Kumar R, R R, Tan Y, Ong PLJ, Tan YLJ, Li JW, Kwek ABE, Ang TL. Clinical trial: seven-day vonoprazan- versus 14-day proton pump inhibitor-based triple therapy for first-line Helicobacter pylori eradication. Aliment Pharmacol Ther 2022; 56:436-449. [PMID: 35665947 DOI: 10.1111/apt.17070] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 03/17/2022] [Accepted: 05/23/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND One-week triple therapy with vonoprazan is endorsed by Japanese guidelines as an alternative to proton pump inhibitor (PPI)-based triple therapy for first-line Helicobacter pylori eradication. This contrasts with Western guidelines recommending 2-week PPI-based triple therapy. AIM To verify the non-inferiority of 1-week vonoprazan-based triple therapy versus 2-week PPI-based triple therapy as first-line H. pylori eradication in a multiracial Asian cohort. METHODS Randomised controlled trial of treatment-naïve patients with H. pylori infection assigned 1:1 to either 7 days amoxicillin 1 g + clarithromycin 500 mg + vonoprazan 20 mg twice per day or 14 days amoxicillin 1 g + clarithromycin 500 mg + omeprazole OR esomeprazole OR rabeprazole 20 mg twice/day. Subjects were randomly assigned to each PPI 1:1:1 Demographics, H. pylori resistance, CYP 2C19 genotype, eradication success and safety profiles were compared between groups. RESULTS Between June 2019 and June 2021, 252 of 1097 subjects screened were randomised. 244 (age [SD] 51.7 [14.6]) received vonoprazan- (n = 119) or PPI-based (n = 125) triple therapy. Eradication rates by intention-to-treat analysis were 87.4% (vonoprazan-based triple therapy) versus 88.0% (PPI-based triple therapy. By per protocol analysis: 96.3% (vonoprazan-based triple therapy) versus 94.0% (PPI-based triple therapy). Clarithromycin resistance predicted treatment failure on multivariate analysis: RR 11.4; 95% CI [1.4-96.3], p = 0.025. No significant differences in CYP 2C19 genotypes or adverse events occurred between groups. CONCLUSION One-week vonoprazan-based triple therapy achieved comparable efficacy to 2-week PPI-based triple therapy and was well tolerated.
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Affiliation(s)
- Daphne Ang
- Department of Gastroenterology, Changi General Hospital, Singapore
| | - Seok Hwee Koo
- Clinical Trials and Research Unit, Changi General Hospital, Singapore
| | - Yiong Huak Chan
- Biostatistics Unit, Yong Yoo Lin School of Medicine, National University of Singapore, Singapore
| | - Thean Yen Tan
- Department of Laboratory Medicine, Changi General Hospital, Singapore
| | - Gaik Hong Soon
- Clinical Trials and Research Unit, Changi General Hospital, Singapore
| | - Chin Kimg Tan
- Department of Gastroenterology, Changi General Hospital, Singapore
| | | | | | - Yu Jun Wong
- Department of Gastroenterology, Changi General Hospital, Singapore
| | - Rahul Kumar
- Department of Gastroenterology, Changi General Hospital, Singapore
| | - Rajesh R
- Department of Gastroenterology, Changi General Hospital, Singapore
| | - Yiyuan Tan
- Department of Gastroenterology, Changi General Hospital, Singapore
| | | | | | - James Weiquan Li
- Department of Gastroenterology, Changi General Hospital, Singapore
| | | | - Tiing Leong Ang
- Department of Gastroenterology, Changi General Hospital, Singapore
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Vital JS, Tanoeiro L, Lopes-Oliveira R, Vale FF. Biomarker Characterization and Prediction of Virulence and Antibiotic Resistance from Helicobacter pylori Next Generation Sequencing Data. Biomolecules 2022; 12:691. [PMID: 35625618 PMCID: PMC9138241 DOI: 10.3390/biom12050691] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 05/02/2022] [Accepted: 05/07/2022] [Indexed: 02/06/2023] Open
Abstract
The Gram-negative bacterium Helicobacter pylori colonizes c.a. 50% of human stomachs worldwide and is the major risk factor for gastric adenocarcinoma. Its high genetic variability makes it difficult to identify biomarkers of early stages of infection that can reliably predict its outcome. Moreover, the increasing antibiotic resistance found in H. pylori defies therapy, constituting a major human health problem. Here, we review H. pylori virulence factors and genes involved in antibiotic resistance, as well as the technologies currently used for their detection. Furthermore, we show that next generation sequencing may lead to faster characterization of virulence factors and prediction of the antibiotic resistance profile, thus contributing to personalized treatment and management of H. pylori-associated infections. With this new approach, more and permanent data will be generated at a lower cost, opening the future to new applications for H. pylori biomarker identification and antibiotic resistance prediction.
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Affiliation(s)
- Joana S. Vital
- Pathogen Genome Bioinformatics and Computational Biology, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal; (J.S.V.); (L.T.); (R.L.-O.)
| | - Luís Tanoeiro
- Pathogen Genome Bioinformatics and Computational Biology, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal; (J.S.V.); (L.T.); (R.L.-O.)
| | - Ricardo Lopes-Oliveira
- Pathogen Genome Bioinformatics and Computational Biology, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal; (J.S.V.); (L.T.); (R.L.-O.)
| | - Filipa F. Vale
- Pathogen Genome Bioinformatics and Computational Biology, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal; (J.S.V.); (L.T.); (R.L.-O.)
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Keikha M, Namdar AB. The presence of DupA and clarithromycin resistance in H. pylori among patients with peptic ulcer disease; a rational connection. GENE REPORTS 2022; 26:101508. [DOI: 10.1016/j.genrep.2022.101508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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Morino Y, Sugimoto M, Nagata N, Niikiura R, Iwata E, Hamada M, Kawai Y, Fujimiya T, Takeuchi H, Unezaki S, Kawai T. Influence of Cytochrome P450 2C19 Genotype on Helicobacter pylori Proton Pump Inhibitor-Amoxicillin-Clarithromycin Eradication Therapy: A Meta-Analysis. Front Pharmacol 2021; 12:759249. [PMID: 34721043 PMCID: PMC8553963 DOI: 10.3389/fphar.2021.759249] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 09/16/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Proton pump inhibitors (PPIs) are the first-line treatment for acid-related diseases. The pharmacokinetics and therapeutic efficacy of PPIs, however, are influenced by genetic factors such as variants in genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19 [CYP2C19]) and drug transporters. We performed a meta-analysis to evaluate the influence of CYP2C19 genotype and PPI class, PPI dose, treatment duration and clarithromycin dose on the cure rate of PPI-containing Helicobacter pylori eradication therapy. Methods: Randomized control trials (RCTs) investigating cure rates using a PPI-amoxicillin-clarithromycin regimen among different CYP2C19 genotypes through May 2021 were included. Results: A total of 25 studies (5,318 patients) were included. The overall eradication rate in the intention-to-treat analysis was 79.0% (3,689/4,669, 95% confidence interval [CI]: 77.8-80.2%), and that in CYP2C19 extensive metabolizers (EMs), intermediate metabolizer (IMs) and poor metabolizers (PMs) was 77.7% (1,137/1,464, 95% CI: 75.3-79.6%), 81.2% (1,498/1,844, 95% CI: 79.3-83.0%) and 86.8% (644/742, 95% CI: 83.9-88.9%), respectively. Meta-analysis showed that the relaTakashitive risk of failed eradication in CYP2C19 EMs compared with IMs and PMs was 1.21 (95% CI: 1.06-1.39, P = 0.006) and 1.57 (95% CI: 1.27-1.94, P < 0.001), respectively, in the fixed-effects model. The cure rate of omeprazole and lansoprazole-containing eradication regimens differed among CYP2C19 genotypes (P < 0.05), while that of rabeprazole and esomeprazole-containing regimens was similar. Conclusion: The cure rates of PPI-amoxicillin-clarithromycin H. pylori eradication regimen, especially those containing omeprazole and lansoprazole, differ among CYP2C19 genotypes. Therefore, selection of a second-generation PPI or tailored treatment may achieve higher eradication rates than first-generation PPI-amoxicillin-clarithromycin triple regimen.
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Affiliation(s)
- Yuko Morino
- Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Mitsushige Sugimoto
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
| | - Naoyoshi Nagata
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
| | - Ryota Niikiura
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
| | - Eri Iwata
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
| | - Mariko Hamada
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
| | - Yusuke Kawai
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
| | - Tatsuhiro Fujimiya
- Department of Practical Pharmacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Hironori Takeuchi
- Department of Pharmacy, Tokyo Medical University Hospital, Tokyo, Japan
| | - Sakae Unezaki
- Department of Practical Pharmacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Takashi Kawai
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
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9
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Isolation of dupA-positive and clarithromycin-resistant Helicobacter pylori from Iranian patients with duodenal ulcer. GENE REPORTS 2021. [DOI: 10.1016/j.genrep.2021.101228] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Karbalaei M, Hussein NR, Keikha M. Predicting the role of dupA-positive Helicobacter pylori strains in severe gastrointestinal disorders: An updated meta-analysis. GENE REPORTS 2021; 24:101263. [DOI: 10.1016/j.genrep.2021.101263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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11
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de Brito BB, Lemos FFB, Carneiro CDM, Viana AS, Barreto NMPV, Assis GADS, Braga BDC, Santos MLC, Silva FAFD, Marques HS, Silva NOE, de Melo FF. Immune response to Helicobacter pylori infection and gastric cancer development. World J Meta-Anal 2021; 9:257-276. [DOI: 10.13105/wjma.v9.i3.257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 04/24/2021] [Accepted: 06/15/2021] [Indexed: 02/06/2023] Open
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Alavifard H, Mirzaei N, Yadegar A, Baghaei K, Smith SM, Sadeghi A, Zali MR. Investigation of Clarithromycin Resistance-Associated Mutations and Virulence Genotypes of Helicobacter pylori Isolated from Iranian Population: A Cross-Sectional Study. Curr Microbiol 2021; 78:244-254. [PMID: 33251569 DOI: 10.1007/s00284-020-02295-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 11/11/2020] [Indexed: 12/17/2022]
Abstract
Antibiotic resistance has brought into question the efficiency of clarithromycin which is a vital component of eradication therapy for Helicobacter pylori infection. The point mutations within the 23S rRNA sequence of H. pylori isolates which contribute to clarithromycin resistance have yet to be fully characterized. This study was aimed to detect clarithromycin resistance-associated mutations and assess the prevalence of key virulence factors of H. pylori among Iranian patients. Amplification of 16S rRNA and glmM genes were done to identify H. pylori. Minimal inhibitory concentration (MIC) of clarithromycin in 82 H. pylori clinical isolates was determined by agar dilution method. Subsequently, various virulence markers including cagA, vacA, sabA, babA, and dupA of H. pylori were identified by PCR. PCR-sequencing was applied to detect point mutations in the 23S rRNA gene. Based on MIC values, 43.9% of H. pylori isolates showed resistance to clarithromycin. The babA and cagA genes were detected in 92.7% and 82.9% of isolates, assigned to be higher than other virulence factors. No significant relationship was found between the H. pylori virulence genotypes and clarithromycin susceptibility (P > 0.05). Analyzing the 23S rRNA sequences revealed A2143G (4/48, 8.3%) and A2142G (3/48, 6.2%) as the most prevalent mutations in clarithromycin-resistant isolates. Additionally, several novel mutations including G2220T, C2248T, A2624C, G2287A, T2188C, G2710C, C2248T, G2269A, and G2224T were also detected among either resistant or susceptible isolates. Our findings revealed the presence of several point mutations in the 23S rRNA gene of H. pylori isolates which may be associated with resistance to clarithromycin.
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Affiliation(s)
- Helia Alavifard
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nasrin Mirzaei
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Kaveh Baghaei
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sinéad Marian Smith
- School of Medicine & School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Baj J, Forma A, Sitarz M, Portincasa P, Garruti G, Krasowska D, Maciejewski R. Helicobacter pylori Virulence Factors-Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment. Cells 2020; 10:27. [PMID: 33375694 PMCID: PMC7824444 DOI: 10.3390/cells10010027] [Citation(s) in RCA: 204] [Impact Index Per Article: 40.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/18/2020] [Accepted: 12/22/2020] [Indexed: 12/11/2022] Open
Abstract
Gastric cancer constitutes one of the most prevalent malignancies in both sexes; it is currently the fourth major cause of cancer-related deaths worldwide. The pathogenesis of gastric cancer is associated with the interaction between genetic and environmental factors, among which infection by Helicobacter pylori (H. pylori) is of major importance. The invasion, survival, colonization, and stimulation of further inflammation within the gastric mucosa are possible due to several evasive mechanisms induced by the virulence factors that are expressed by the bacterium. The knowledge concerning the mechanisms of H. pylori pathogenicity is crucial to ameliorate eradication strategies preventing the possible induction of carcinogenesis. This review highlights the current state of knowledge and the most recent findings regarding H. pylori virulence factors and their relationship with gastric premalignant lesions and further carcinogenesis.
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Affiliation(s)
- Jacek Baj
- Department of Anatomy, Medical University of Lublin, 20-400 Lublin, Poland;
| | - Alicja Forma
- Chair and Department of Forensic Medicine, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Monika Sitarz
- Department of Conservative Dentistry with Endodontics, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Piero Portincasa
- Clinica Medica “Augusto Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy;
| | - Gabriella Garruti
- Section of Endocrinology, Department of Emergency and Organ Transplantations, University of Bari “Aldo Moro” Medical School, Piazza G. Cesare 11, 70124 Bari, Italy;
| | - Danuta Krasowska
- Department of Dermatology, Venerology and Paediatric Dermatology of Medical University of Lublin, 20-081 Lublin, Poland;
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Sugimoto M, Hira D, Murata M, Kawai T, Terada T. Effect of Antibiotic Susceptibility and CYP3A4/5 and CYP2C19 Genotype on the Outcome of Vonoprazan-Containing Helicobacter pylori Eradication Therapy. Antibiotics (Basel) 2020; 9:645. [PMID: 32993151 PMCID: PMC7599771 DOI: 10.3390/antibiotics9100645] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 09/24/2020] [Accepted: 09/24/2020] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Helicobacter pylori eradication containing the potassium-competitive acid blocker, vonoprazan, achieves a higher eradication rate than therapy with proton pump inhibitors (PPIs). Because vonoprazan is mainly metabolized by CYP3A4/5, CYP genotype may affect the eradication rate. We investigated the influence of antibiotic susceptibility and CYP3A4/5 and CYP2C19 genotypes on the eradication rates. METHODS A total of 307 Japanese who were genotyped for CYP3A4 *1/*22, CYP3A5 *1/*3 and CYP2C19 *1/*2/*3/*17, and investigated for susceptibility to antimicrobial agents, received vonoprazan-containing regimens: (1) With amoxicillin and clarithromycin as the first-line treatment; (2) with amoxicillin and metronidazole as the second-line treatment; or (3) with amoxicillin and sitafloxacin as the third-line treatment. RESULTS The eradication rate was 84.5% (95% confidence interval [CI]: 78.9-89.1%) using first-line, 92.6% (95% CI: 82.1-97.9%) using second-line and 87.5% (95% CI: 73.1-95.8%) using third-line treatment. Infection with clarithromycin-resistant strains was a predictive factor for failed eradication (odds ratio: 5.788, 95% CI: 1.916-17.485, p = 0.002) in multivariate analysis. No significant differences were observed in the eradication rate of regimens among CYP3A4, CYP3A5 and CYP2C19 genotypes. CONCLUSIONS Genotyping for CYP3A4 *1/*22, CYP3A5 *1/*3 and CYP2C19 *1/*2/*3/*17 before vonoprazan-containing eradication treatment may not be useful for predicting clinical outcomes.
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Affiliation(s)
- Mitsushige Sugimoto
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Shinjuku, Tokyo 160-0023, Japan;
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu, Shiga 520-2192, Japan
| | - Daiki Hira
- Department of Pharmacy, Shiga University of Medical Science Hospital, Otsu, Shiga 520-2192, Japan; (D.H.); (T.T.)
- College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan
| | - Masaki Murata
- Department of Gastroenterology, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan;
| | - Takashi Kawai
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Shinjuku, Tokyo 160-0023, Japan;
| | - Tomohiro Terada
- Department of Pharmacy, Shiga University of Medical Science Hospital, Otsu, Shiga 520-2192, Japan; (D.H.); (T.T.)
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15
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Alam J, Sarkar A, Karmakar BC, Ganguly M, Paul S, Mukhopadhyay AK. Novel virulence factor dupA of Helicobacter pylori as an important risk determinant for disease manifestation: An overview. World J Gastroenterol 2020; 26:4739-4752. [PMID: 32921954 PMCID: PMC7459207 DOI: 10.3748/wjg.v26.i32.4739] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 06/23/2020] [Accepted: 08/03/2020] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a microaerophilic, Gram-negative, human gastric pathogen found usually in the mucous lining of stomach. It infects more than 50% of the world’s population and leads to gastroduodenal diseases. The outcome of disease depends on mainly three factors: Host genetics, environment and bacterial factors. Among these, bacterial virulence factors such as cagA, vacA are well known for their role in disease outcomes. However, based on the global epidemiological results, none of the bacterial virulence (gene) factors was found to be associated with particular diseases like duodenal ulcer (DU) in all populations. Hence, substantial importance has been provided for research in strain-specific genes outside the cag pathogenicity island, especially genes located within the plasticity regions. dupA found within the plasticity regions was first demonstrated in 2005 and was proposed for duodenal ulcer development and reduced risk of gastric cancer in certain geographical regions. Due to the discrepancies in report from different parts of the world in DU development related to H. pylori virulence factor, dupA became an interesting area of research in elucidating the role of this gene in the disease progression. In this review, we shed light on the detailed information available on the polymorphisms in dupA and their clinical relevance. We have critically appraised several pertinent studies on dupA and discussed their merits and shortcomings. This review also highlights dupA gene as an important biomarker for DU in certain populations.
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Affiliation(s)
- Jawed Alam
- Division of Infectious Diseases, Institute of Life Science, Bhubaneswar 751023, India
| | - Avijit Sarkar
- Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata 700010, India
| | - Bipul Chandra Karmakar
- Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata 700010, India
| | - Mou Ganguly
- Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata 700010, India
| | - Sangita Paul
- Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata 700010, India
| | - Asish K Mukhopadhyay
- Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata 700010, India
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Šterbenc A, Jarc E, Poljak M, Homan M. Helicobacter pylori virulence genes. World J Gastroenterol 2019; 25:4870-4884. [PMID: 31543679 PMCID: PMC6737321 DOI: 10.3748/wjg.v25.i33.4870] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 07/29/2019] [Accepted: 08/07/2019] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is one of the most important human pathogens, infecting approximately half of the global population. Despite its high prevalence, only a subset of H. pylori infected individuals develop serious gastroduodenal pathology. The pathogenesis of H. pylori infection and disease outcome is thus thought to be mediated by an intricate interplay between host, environmental and bacterial virulence factors. H. pylori has adapted to the harsh milieu of the human stomach through possession of various virulence genes that enable survival of the bacteria in the acidic environment, movement towards the gastric epithelium, and attachment to gastric epithelial cells. These virulence factors enable successful colonization of the gastric mucosa and sustain persistent H. pylori infection, causing chronic inflammation and tissue damage, which may eventually lead to the development of peptic ulcers and gastric cancer. Numerous studies have focused on the prevalence and role of putative H. pylori virulence genes in disease pathogenesis. While several virulence factors with various functions have been identified, disease associations appear to be less evident, especially among different study populations. This review presents key findings on the most important H. pylori virulence genes, including several bacterial adhesins and toxins, in children and adults, and focuses on their prevalence, clinical significance and potential relationships.
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Affiliation(s)
- Anja Šterbenc
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Erika Jarc
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Mario Poljak
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Matjaž Homan
- Department of Gastroenterology, Hepatology and Nutrition, University Children’s Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
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Sugimoto M, Yamaoka Y. Role of Vonoprazan in Helicobacter pylori Eradication Therapy in Japan. Front Pharmacol 2019; 9:1560. [PMID: 30697158 PMCID: PMC6340927 DOI: 10.3389/fphar.2018.01560] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Accepted: 12/21/2018] [Indexed: 12/11/2022] Open
Abstract
Complete eradication of Helicobacter pylori is important for preventing the development of gastric cancer. The outcome of H. pylori eradication therapy is mainly dependent on bacterial susceptibility to antimicrobial agents and potent neutralization of intragastric pH across 24 h, especially when using acid-sensitive antimicrobial agents such as clarithromycin (CLR), amoxicillin and sitafloxacin. However, conventional regimens comprising twice-daily doses (bid) of proton pump inhibitors (PPIs) are generally insufficient for maintaining the required gastric acid secretion for 24 h for successful eradication in all H. pylori-positive patients. Further, the increasing prevalence of CLR-resistant strains with each year has led to a decrease in eradication rates of first-line PPI- and CLR-containing therapies in developed countries, including Japan. In 2015, the potassium-competitive acid blocker vonoprazan (VPZ) became clinically available in Japan. VPZ competitively inhibits H+/K+-ATPase activity more potently than PPIs (e.g., omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole). Therefore, a VPZ-containing H. pylori eradication regimen is expected to increase the eradication rate compared with conventional regimens containing a standard dose of PPI. In fact, a recent meta-analysis that investigated the efficacy of first-line eradication therapy showed that a VPZ-containing regimen achieved a higher eradication rate than a PPI-containing regimen. While the Maastricht V/Florence Consensus Report recommends selecting a bismuth or non-bismuth quadruple therapy and concomitant therapy for patients living in areas with high prevalence of CLR resistance, a VPZ-containing regimen demonstrates effectiveness for patients infected with CLR-resistant strains and patients living in areas where the prevalence of CLR-resistant strains is >15%. As a next step, studies are needed to determine the factors affecting the clinical outcome of VPZ-containing therapy and optimal VPZ-containing alternative regimens for tailored treatments. In this review, we summarize the advantages and disadvantages of VPZ in H. pylori eradication therapy.
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Affiliation(s)
- Mitsushige Sugimoto
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu, Japan
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan
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de Brito BB, da Silva FAF, de Melo FF. Role of polymorphisms in genes that encode cytokines and Helicobacter pylori virulence factors in gastric carcinogenesis. World J Clin Oncol 2018; 9:83-89. [PMID: 30254963 PMCID: PMC6153128 DOI: 10.5306/wjco.v9.i5.83] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Revised: 06/23/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
The Helicobacter pylori (H. pylori) infection is a determinant factor in gastric cancer (GC) development. However, the infection outcomes are variable and depend on both host and bacterial characteristics. Some host cytokines such as interleukin (IL)-1β, IL-1Ra, IL-8, IL-10 and tumor necrosis factor-α play important roles in the host immune system response to the pathogen, in the development of gastric mucosal lesions and in cell malignant transformation. Therefore, these host factors are crucial in neoplastic processes. Certain polymorphisms in genes that encode these cytokines have been associated with an increased risk of GC. On the other hand, various virulence factors found in distinct H. pylori bacterial strains, including cytotoxin-associated antigen A, vacuolating cytotoxin, duodenal ulcer promoting gene A protein, outer inflammatory protein and blood group antigen binding adhesin, have been associated with the pathogenesis of different gastric diseases. The virulent factors mentioned above allow the successful infection by the bacterium and play crucial roles in gastric mucosa lesions, including malignant transformation. Moreover, the role of host polymorphisms and bacterial virulence factors in gastric carcinogenesis seems to vary among different countries and populations. The identification of host and bacterium factors that are associated with an increased risk of GC development may be useful in determining the prognosis of infection in patients, what could help in clinical decision-making and in providing of an optimized clinical approach.
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Affiliation(s)
- Breno Bittencourt de Brito
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Brazil
| | | | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Brazil
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Abu-Taleb AMF, Abdelattef RS, Abdel-Hady AA, Omran FH, El-korashi LA, Abdel-aziz El-hady H, El-Gebaly AM. Prevalence of Helicobacter pylori cagA and iceA Genes and Their Association with Gastrointestinal Diseases. Int J Microbiol 2018; 2018:4809093. [PMID: 29849647 PMCID: PMC5907521 DOI: 10.1155/2018/4809093] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Revised: 02/15/2018] [Accepted: 02/20/2018] [Indexed: 12/20/2022] Open
Abstract
H. pylori infection causes peptic ulcer, chronic gastritis, mucosa-associated lymphoid tissue lymphoma, and gastric carcinoma. It has several virulence factors such as cytotoxin-associated gene A(cagA) and the induced by contact with epithelium antigen (iceA). We aimed to explore the relationship between cagA and iceA of H. pylori and gastrointestinal diseases. One hundred and eighteen patients who attended Gastrointestinal Endoscopy Unit at Zagazig University Hospitals, Egypt, were included in this study. Two gastric biopsies were collected and evaluated by rapid urease test (RUT) and PCR. cagA and iceA genes were amplified by PCR. We found that 54 patients (45.76%) were positive by both RUT and PCR. cagA and iceA genes were present in 57.4% and 46.29% of the studied patients, respectively. cagA was the most prevalent gene in gastritis (33.3%) and peptic ulcer (68.7%). iceA1/iceA2 positive genes were the most prevalent in gastric cancer (75%). iceA1 gene was present in 38.7% of cagA positive cases, but iceA2 gene was present in 45.2% of cagA positive cases. iceA1/iceA2 positive genes were present in 29% of cagA positive cases. In conclusion, cagA and iceA genes could be used as markers for severe gastrointestinal diseases. iceA gene was strongly related to cagA gene.
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Affiliation(s)
- Ashwak M. F. Abu-Taleb
- Medical Microbiology and Immunology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Randa S. Abdelattef
- Medical Microbiology and Immunology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Amina A. Abdel-Hady
- Medical Microbiology and Immunology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Farida H. Omran
- Medical Microbiology and Immunology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Lobna A. El-korashi
- Medical Microbiology and Immunology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | | | - Ahmed M. El-Gebaly
- Tropical Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt
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20
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Gong Y, Yuan Y. Resistance mechanisms of Helicobacter pylori and its dual target precise therapy. Crit Rev Microbiol 2018; 44:371-392. [PMID: 29293032 DOI: 10.1080/1040841x.2017.1418285] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Helicobacter pylori drug resistance presents a significant challenge to the successful eradication of this pathogen. To find strategies to improve the eradication efficacy of H. pylori, it is necessary to clarify the resistance mechanisms involved. The mechanisms of H. pylori drug resistance can be investigated from two angles: the pathogen and the host. A comprehensive understanding of the molecular mechanisms of H. pylori resistance based on both pathogen and host would aid the implementation of precise therapy, or ideally "dual target precise therapy" (bacteria and host-specific target therapy). In recent years, with increased understanding of the mechanisms of H. pylori resistance, the focus of eradication has shifted from disease-specific to patient-specific treatment. The implementation of "precision medicine" has also provided a new perspective on the treatment of infectious diseases. In this article, we systematically review current research on H. pylori drug resistance from the perspective of both the pathogen and the host. We also review therapeutic strategies targeted to pathogen and host factors that are aimed at achieving precise treatment of H. pylori.
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Affiliation(s)
- Yuehua Gong
- a Tumor Etiology and Screening Department of Cancer Institute and General Surgery , the First Hospital of China Medical University , Shenyang , China.,b Key Laboratory of Cancer Etiology and Prevention (China Medical University) Liaoning Provincial Education Department , Shenyang , China.,c National Clinical Research Center for Digestive Diseases , Xi'an , China
| | - Yuan Yuan
- a Tumor Etiology and Screening Department of Cancer Institute and General Surgery , the First Hospital of China Medical University , Shenyang , China.,b Key Laboratory of Cancer Etiology and Prevention (China Medical University) Liaoning Provincial Education Department , Shenyang , China.,c National Clinical Research Center for Digestive Diseases , Xi'an , China
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21
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Zhang SH, Zhu X, Li BM, Li H. The effect of virulence genotypes of Helicobacter pylori on eradication therapy in children. Saudi J Gastroenterol 2018; 24:249-254. [PMID: 29652033 PMCID: PMC6080151 DOI: 10.4103/sjg.sjg_579_17] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND/AIM It is important to eradicate Helicobacter pylori at an early stage in patients during childhood to potentially prevent the development of H. pylori-related diseases. Studies have demonstrated that the virulence genotype of H. pylori influences the efficacy of eradication therapy. The efficacy of triple therapy has decreased significantly, which has seriously affected the clinical outcome of children with H. pylori infection. In this study we aimed to investigate the influence of virulence genotypes of H. pylori on triple eradication therapy in children. PATIENTS AND METHODS H. pylori strains were isolated from the gastric antrum mucosa in children with upper gastrointestinal symptoms. Polymerase chain reaction (PCR) was conducted to determine the H. pylori cagA, vacA, and iceA genotypes. All patients with H. pylori infection were administered 14-day triple therapy. After drug withdrawal for at least 4 weeks, the 13C-urea breath test (13C-UBT) was used to observe the therapeutic effect of H. pylori eradication. The eradication rates were evaluated by intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS A total of 107 patients were enrolled in this study. Nine patients were lost to follow-up, and 98 patients were administered eradication therapy. Based on ITT and PP analyses, the H. pylori eradication rate was 64.5% (69/107) and 70.4% (69/98), respectively. Among the successful eradication groups, the cagA-positive, vacA s1a, vacA s1c, vacA m1, vacA m2, iceA 1, and iceA 2 genes were identified in 72.8%, 68.1%, 76.9%, 60.0%, 74.6%, 71.8%, and 75.0% of strains, respectively. Of the unsuccessful eradication groups, the cagA-positive, vacA s1a, vacA s1c, vacA m1, vacA m2, iceA 1, and iceA 2 genes were identified in 27.2%, 31.9%, 23.1%, 40.0%, 25.4%, 28.2%, and 25.0% of strains, respectively. No statistically significant differences were noted in the detection rate of the H. pylori genotypes between the H. pylori successful and unsuccessful eradication groups (P > 0.05). CONCLUSIONS The cagA, vacA, and iceA genotypes of H. pylori are not associated with the efficacy of omeprazole-based triple therapy on the eradication of H. pylori infection in children.
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Affiliation(s)
- Shuang-Hong Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China
| | - Xuan Zhu
- Department of Gastroenterology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China,Address for correspondence: Dr. Xuan Zhu, Department of Gastroenterology, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, - 330006, Jiangxi Province, China. E-mail:
| | - Bi-Min Li
- Department of Gastroenterology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China
| | - Hong Li
- Central Laboratory, Children's Hospital of Jiangxi, Nanchang, Jiangxi Province, China
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22
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Wang D, Li Q, Gong Y, Yuan Y. The association between vacA or cagA status and eradication outcome of Helicobacter pylori infection: A meta-analysis. PLoS One 2017; 12:e0177455. [PMID: 28493953 PMCID: PMC5426689 DOI: 10.1371/journal.pone.0177455] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Accepted: 04/27/2017] [Indexed: 12/14/2022] Open
Abstract
Background H. pylori virulence factors, especially vacA and cagA are important in gastroduodenal disease pathogenesis and affect cure rates. This meta-analysis aimed to clarify the association between vacA or cagA status and eradication outcome of H. pylori infection. Methods A literature search was performed using electronic databases to identify studies. Twenty-six prospective studies were determined eligible. Meta-analytical techniques were conducted to calculate eradication rates and pooled relative ratios (RR). Results The eradication rate was greater approximately 10% in vacA s1 compared with vacA s2 infected patients, and the pooled RR was 1.164 (95%CI: 1.040–1.303, P = 0.008). A significant association existed between vacA s1 and higher eradication rates in Europe (RR: 1.203, 95%CI: 1.003–1.442, P = 0.046) and Asia (RR: 1.187, 95%CI: 1.028–1.371, P = 0.020), in triple therapy patients (RR: 1.175, 95%CI: 1.012–1.365, P = 0.035). Eradication rates were similar for vacA m1 and m2 genotypes (RR: 0.981, 95%CI: 0.891–1.080, P = 0.690), whereas they were higher by approximately 8% in cagA-positive compared with cagA-negative infected patients, with a pooled RR of 1.094 (95%CI: 1.025–1.168, P = 0.007). A significant association existed between cagA-positive and increased eradication rates in Europe (RR: 1.138, 95%CI: 1.000–1.295, P = 0.049) and Asia (RR: 1.118, 95%CI: 1.051–1.190, P<0.001), in using PCR (RR: 1.232, 95%CI: 1.142–1.329, P<0.001) and protein chips (RR: 1.200, 95%CI: 1.060–1.359, P = 0.004), in triple therapy patients (RR: 1.090, 95%CI: 1.006–1.181, P = 0.034). Conclusions Evidence indicates that infection with vacA s1, cagA-positive strains, but not vacA s2, cagA-negative, is more conducive to H. pylori eradication.
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Affiliation(s)
- Dan Wang
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China
| | - Qiuping Li
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China
| | - Yuehua Gong
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China
- * E-mail: (GY); (YY)
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China
- * E-mail: (GY); (YY)
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Zhang X, Jiang A, Wang G, Yu H, Qi B, Xiong Y, Zhou G, Qin M, Dou J, Wang J. Fusion expression of the PGLa-AM1 with native structure and evaluation of its anti-Helicobacter pylori activity. Appl Microbiol Biotechnol 2017; 101:5667-5675. [PMID: 28488117 DOI: 10.1007/s00253-017-8302-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Revised: 03/28/2017] [Accepted: 04/18/2017] [Indexed: 12/26/2022]
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Talebi Bezmin Abadi A, Perez-Perez G. Role of dupA in virulence of Helicobacter pylori. World J Gastroenterol 2016; 22:10118-10123. [PMID: 28028359 PMCID: PMC5155170 DOI: 10.3748/wjg.v22.i46.10118] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Revised: 09/27/2016] [Accepted: 11/14/2016] [Indexed: 02/07/2023] Open
Abstract
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.
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Bagheri N, Azadegan-Dehkordi F, Rafieian-Kopaei M, Rahimian G, Asadi-Samani M, Shirzad H. Clinical relevance of Helicobacter pylori virulence factors in Iranian patients with gastrointestinal diseases. Microb Pathog 2016; 100:154-162. [PMID: 27666510 DOI: 10.1016/j.micpath.2016.09.016] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Revised: 09/21/2016] [Accepted: 09/21/2016] [Indexed: 12/21/2022]
Abstract
Helicobacter pylori (H. pylori) usually colonizes the gastric mucosa of more than 50% of the human population, causing an infection that may appear in early childhood and can persist for life. H. pylori is suggested as the main cause of peptic ulcer and chronic gastritis. It is also associated with gastric cancer. Its severity and symptoms depend on environmental factors, host susceptibility and bacterial components, which allow H. pylori to switch between commensalism and pathogenicity. H. pylori is genetically highly variable, and the variability which affects H. pylori virulence factors might be useful in identifying the strains with different degrees of pathogenicity. The geographic distribution of distinct H. pylori genotypes is largely unknown and should be established. The prevalence of more pathogenic genotypes in certain areas may have important epidemiological consequences. It also might be associated with the severity of H. pylori related diseases in such regions. Given that Iran is located in the Middle East and Asian populations have revealed high levels of gastric cancer, it is of clinical interest to clarify the potential of H. pylori virulence markers in predicting the associated clinical outcomes. In this review, clinical relevance of adhesion molecules and significant virulence factors of H. pylori in Iranian patients with gastrointestinal diseases are discussed in comparison to other countries.
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Affiliation(s)
- Nader Bagheri
- Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran; Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | | | | | - Ghorbanali Rahimian
- Department of Internal Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Majid Asadi-Samani
- Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Hedaytollah Shirzad
- Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.
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Miftahussurur M, Yamaoka Y. Population-Based Strategies for Helicobacter pylori-Associated Disease Management: Asian Perspective. HELICOBACTER PYLORI RESEARCH 2016:519-542. [DOI: 10.1007/978-4-431-55936-8_23] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Lee JY. Triple Therapy. HELICOBACTER PYLORI 2016:427-436. [DOI: 10.1007/978-981-287-706-2_41] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Uotani T, Miftahussurur M, Yamaoka Y. Effect of bacterial and host factors on Helicobacter pylori eradication therapy. Expert Opin Ther Targets 2015; 19:1637-50. [PMID: 26245678 DOI: 10.1517/14728222.2015.1073261] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION A clearer understanding of the factors affecting the cure rate of Helicobacter pylori infection might lead to the development of novel prevention strategies and therapeutic targets. AREAS COVERED This review covers two important issues that affect the eradication of H. pylori: bacterial and host factors. Several virulence factors have been shown to be predictors for gastroduodenal diseases. Successful treatment of H. pylori infection also depends on host genetic factors such as CYP2C19 and IL-1B. The latest evidence on host genetic factors is discussed. EXPERT OPINION The authors identify three main targets for achieving effective eradication therapy. The first therapeutic target is to identify counter measures for antibiotic-resistant H. pylori strains. Thus, antibiotic susceptibility should be checked in all patients, ideally, before the start of eradication treatment. The second therapeutic target is the inhibition of acid suppression. Maintaining a high intragastric pH for 24 h increases the effectiveness of some antibiotics and the eradication effects for H. pylori. The third therapeutic target is to identify high-risk groups; the CYP2C19 and IL-1B polymorphisms are candidates for significant risk factors. A personalized medical approach will likely increase the cure rate of H. pylori infection.
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Affiliation(s)
- Takahiro Uotani
- a 1 Oita University Faculty of Medicine, Department of Environmental and Preventive Medicine , 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan +81 97 586 5740 ; +81 97 586 5749 ; .,b 2 Baylor College of Medicine and Michael DeBakey Veterans Affairs Medical Center, Department of Gastroenterology and Hepatology , Houston, TX 77030, USA
| | - Muhammad Miftahussurur
- a 1 Oita University Faculty of Medicine, Department of Environmental and Preventive Medicine , 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan +81 97 586 5740 ; +81 97 586 5749 ; .,c 3 Airlangga University, Institute of Tropical Disease , Surabaya 60115, Indonesia
| | - Yoshio Yamaoka
- a 1 Oita University Faculty of Medicine, Department of Environmental and Preventive Medicine , 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan +81 97 586 5740 ; +81 97 586 5749 ; .,b 2 Baylor College of Medicine and Michael DeBakey Veterans Affairs Medical Center, Department of Gastroenterology and Hepatology , Houston, TX 77030, USA
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Hussein NR, Tunjel I, Majed HS, Yousif ST, Aswad SI, Assafi MS. Duodenal ulcer promoting gene 1 (dupA1) is associated with A2147G clarithromycin-resistance mutation but not interleukin-8 secretion from gastric mucosa in Iraqi patients. New Microbes New Infect 2015; 6:5-10. [PMID: 26042186 PMCID: PMC4442689 DOI: 10.1016/j.nmni.2015.02.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2014] [Revised: 02/11/2015] [Accepted: 02/24/2015] [Indexed: 12/13/2022] Open
Abstract
Helicobacter pylori causes peptic ulceration and gastric adenocarcinoma. The aims were to study the influence of dupA1 positivity upon interleukin-8 (IL-8) secretion from gastric mucosa and determine the prevalence of mutations responsible for clarithromycin and fluoroquinolone resistance. DNA was extracted from 74 biopsies and the virulence factors were studied. Levels of IL-8 in gastric mucosa were measured using ELISA and the mutations responsible for clarithromycin and fluoroquinolone resistance were determined using a GenoType-HelicoDR assay. The prevalence of cagA in strains isolated from gastric ulcer (GU) and duodenal ulcer (DU) was significantly higher than those isolated from non-ulcer disease (NUD) (90% and 57.9% versus 33.3%; p 0.01). The vacA s1m1 genotype was more prevalent in patients with DU (73.7%) and GU (70%) than in those with NUD (13.3%) (p 0.01). The prevalence of dupA1 was higher in DU patients (36.8%) than those with GU (10%) and NUD (8.9%) (p 0.01). Multivariate analysis showed that a cagA+/vacA s1i1m2 virulence gene combination was independently associated with the developing peptic ulcer disease (PUD) with increased odds of developing PUD (p 0.03; OR = 2.1). We found no significant difference in the levels of IL-8 secretion in gastric mucosa infected with H. pylori dupA-negative and H. pylori dupA1-positive strains (dupA-negative: mean ± median: 28 ± 26 versus 30 ± 27.1 for dupA1; p 0.6). While 12 strains were clarithromycin resistant, only three isolates were levofloxacin resistant. A significant association was found between dupA1 genotype and A2147G clarithromycin resistance mutation (p <0.01). Further study is needed to explore the relationship between virulence factors and disease process and treatment failure.
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Affiliation(s)
- N R Hussein
- Department of Internal Medicine, The School of Medical Sciences, Faculty of Medicine, University of Duhok, Kurdistan Region, Iraq
| | - I Tunjel
- Department of Biology, Faculty of Science, Fatih University, Istanbul, Turkey
| | - H S Majed
- Nutrition Unit, Duhok Diabetes Centre, Duhok, Kurdistan Region, Iraq
| | - S T Yousif
- Department of Internal Medicine, The School of Medical Sciences, Faculty of Medicine, University of Duhok, Kurdistan Region, Iraq
| | - S I Aswad
- Department of Internal Medicine, The School of Medical Sciences, Faculty of Medicine, University of Duhok, Kurdistan Region, Iraq
| | - M S Assafi
- Department of Biology, Faculty of Sciences, University of Zakho, Kurdistan Region, Iraq
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Sugimoto M, Furuta T. Efficacy of tailored Helicobacter pylori eradication therapy based on antibiotic susceptibility and CYP2C19 genotype. World J Gastroenterol 2014; 20:6400-6411. [PMID: 24914361 PMCID: PMC4047325 DOI: 10.3748/wjg.v20.i21.6400] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2013] [Revised: 01/18/2014] [Accepted: 02/17/2014] [Indexed: 02/06/2023] Open
Abstract
The cure rates of Helicobacter pylori (H. pylori) eradication therapy using a proton pump inhibitor (PPI) and antimicrobial agents such as amoxicillin, clarithromycin, and metronidazole are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of the inhibition of acid secretion. Annual cure rates have gradually decreased because of the increased prevalence of H. pylori strains resistant to antimicrobial agents, especially to clarithromycin. Alternative regimens have therefore been developed incorporating different antimicrobial agents. Further, standard PPI therapy (twice-daily dosing) often fails to induce a long-term increase in intragastric pH > 4.0. Increasing the eradication rate requires more frequent and higher doses of PPIs. Therapeutic efficacy related to acid secretion is influenced by genetic factors such as variants of the genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19, CYP2C19), drug transporters (e.g., multidrug resistance protein-1; ABCB1), and inflammatory cytokines (e.g., interleukin-1β). For example, quadruple daily administration of PPI therapy potently inhibits acid secretion within 24 h, irrespective of CYP2C19 genotype. Therefore, tailored H. pylori eradication regimens that address acid secretion and employ optimal antimicrobial agents based on results of antimicrobial agent-susceptibility testing may prove effective in attaining higher eradication rates.
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Kim JY, Kim N, Nam RH, Suh JH, Chang H, Lee JW, Kim YS, Kim JM, Choi JW, Park JG, Lee YS, Lee DH, Jung HC. Association of polymorphisms in virulence factor of Helicobacter pylori and gastroduodenal diseases in South Korea. J Gastroenterol Hepatol 2014; 29:984-91. [PMID: 24372834 DOI: 10.1111/jgh.12509] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/04/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Clinical outcomes of Helicobacter pylori (HP) infection have been shown to be dependent on the variability of virulence factors. The aim of this study was to evaluate the prevalence of each virulence factor and the association between polymorphisms of the virulence factors of HP, and the clinical outcome of gastroduodenal diseases in South Korea. METHODS Four hundred one HP colonies were analyzed (75 colonies from 45 controls; 71 colonies from 39 benign gastric ulcer [BGU] patients; 102 colonies from 54 duodenal ulcer [DU] patients; 121 colonies from 77 stomach cancer patients; and 32 colonies from 25 dysplasia patients). Polymerase chain reaction amplifications for vacA, cagA, iceA, oipA, and dupA were performed using DNA extract from HP isolates cultured from mucosal biopsy specimens. dupA was regarded as positive when all of jph0718, jph0719, and dupA were positive. RESULTS Most colonies were composed of vacA s1 (100.0%), i1 (100.0%) and m1 (92.9%), cagA-positive (87.2%), iceA1 (95.8%), oipA-positive (91.2%), and dupA-negative (52.0%) genotypes. dupA was more frequently expressed in BGU (81.3%), DU (74.7%), and dysplasia (41.7%) than control (16.7%) (P < 0.001). Infection by dupA-positive HP showed an increased risk of BGU (odds ratio 33.06, 95% confidence interval 11.91-91.79) and DU (odds ratio 15.60, 95% confidence interval 6.49-37.49). CONCLUSION HP infection in South Koreans appears to be closely related to highly virulent strains (vacA s1/i1/m1, cagA(+), iceA1(+), and oipA(+)), except dupA. dupA has an intimate association with the development of peptic ulcer diseases.
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Affiliation(s)
- Ji Yeon Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine
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Cid TP, Fernández MC, Benito Martínez S, Jones NL. Pathogenesis of Helicobacter pylori infection. Helicobacter 2013; 18 Suppl 1:12-7. [PMID: 24011239 DOI: 10.1111/hel.12076] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori infection and disease outcome are mediated by a complex interplay between bacterial, host, and environmental factors. Over the past year, our understanding of this complex interplay has been improved by a variety of studies focusing on both host and bacterial factors. These include studies assessing novel virulence factors as well as those most frequently associated with severity of disease outcome including cagA and the cag pathogenicity island, and the vacuolating cytotoxin. Several studies have focused on regulation of virulence factors by environmental factors. In addition, mechanisms by which bacterial virulence factors influence the host response and disease, by inducing epigenetic changes, autophagy and altered oxidative stress have also been elucidated. This review highlights key findings in the pathogenesis of H. pylori infection reported over the past year.
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Affiliation(s)
- Trinidad Parra Cid
- Unidad de Investigación, Hospital Universitario de Guadalajara, Guadalajara, Spain; CIBERehd (Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas), Madrid, Spain
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Abstract
Helicobacter pylori (H. pylori) infection is linked to various gastroduodenal diseases; however, only a small fraction of these patients develop associated diseases. Despite the high prevalence of H. pylori infection in Africa and South Asia, the incidence of gastric cancer in these areas is much lower than those in other countries. The incidence of gastric cancer tends to decrease from north to south in East Asia. Such geographical differences in the pathology can be explained, at least in part, by the presence of different types of H. pylori virulence factors in addition to host and environmental factors. Virulence factors of H. pylori, such as CagA, VacA, DupA, IceA, OipA and BabA, have been demonstrated to be the predictors of severe clinical outcomes. Interestingly, a meta-analysis showed that CagA seropositivity was associated with gastric cancer compared with gastritis, even in East Asian countries where almost the strains possess cagA. Another meta-analysis also confirmed the significance of vacA, dupA and iceA. However, it is possible that additional important pathogenic genes may exist because H. pylori consists of approximately 1600 genes. Despite the advances in our understanding of the development of H. pylori infection-related diseases, further work is required to clarify the roles of H. pylori virulence factors.
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Affiliation(s)
- Seiji SHIOTA
- Department of Environmental and Preventive Medicine, Yufu-City, Oita, Japan
,Department of General Medicine, Oita University Faculty of Medicine, Yufu-City, Oita, Japan
| | - Rumiko SUZUKI
- Department of Environmental and Preventive Medicine, Yufu-City, Oita, Japan
| | - Yoshio YAMAOKA
- Department of Environmental and Preventive Medicine, Yufu-City, Oita, Japan
,Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas, USA
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Shiota S, Murakawi K, Suzuki R, Fujioka T, Yamaoka Y. Helicobacter pylori infection in Japan. Expert Rev Gastroenterol Hepatol 2013; 7:35-40. [PMID: 23265147 PMCID: PMC3732492 DOI: 10.1586/egh.12.67] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The prevalence of Helicobacter pylori infection is gradually decreasing in Japan. On the main island of Japan, nearly all H. pylori isolates possess cagA and vacA with strong virulence. However, less virulent H. pylori strains are frequently found in Okinawa where cases of gastric cancer are the lowest in Japan. Eradication therapy for peptic ulcer, idiopathic thrombocytopenic purpura, gastric mucosa-associated lymphoid tissue lymphoma and early gastric cancer after endoscopic resection has been approved by the Japanese national health insurance system. However, the Japanese Society for Helicobacter Research recently stated that all 'H. pylori infection' was considered as the indication for eradication irrespective of the background diseases. To eliminate H. pylori in Japan, the Japanese health insurance system should approve the eradication of all H. pylori infections.
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Affiliation(s)
- Seiji Shiota
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu City, Oita 879-5593, Japan,Department of General Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu City, Oita 879-5593, Japan
| | - Kazunari Murakawi
- Department of General Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu City, Oita 879-5593, Japan
| | - Rumiko Suzuki
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu City, Oita 879-5593, Japan
| | - Toshio Fujioka
- Department of General Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu City, Oita 879-5593, Japan
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu City, Oita 879-5593, Japan,Department of Medicine–Gastroenterology, Baylor College of Medicine and Michael E. Debakey Veterans Affairs Medical Center, 2002 Holcombe Blvd. Houston, TX 77030, USA,Author for correspondence: Tel.: +81 975 865 740, Fax: +81 975 865 749,
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