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Skokowski J, Vashist Y, Girnyi S, Cwalinski T, Mocarski P, Antropoli C, Brillantino A, Boccardi V, Goyal A, Ciarleglio FA, Almohaimeed MA, De Luca R, Abou-Mrad A, Marano L, Oviedo RJ, Januszko-Giergielewicz B. The Aging Stomach: Clinical Implications of H. pylori Infection in Older Adults-Challenges and Strategies for Improved Management. Int J Mol Sci 2024; 25:12826. [PMID: 39684537 PMCID: PMC11641014 DOI: 10.3390/ijms252312826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 10/25/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024] Open
Abstract
Aging is a multifactorial biological process characterized by a decline in physiological function and increasing susceptibility to various diseases, including malignancies and gastrointestinal disorders. Helicobacter pylori (H. pylori) infection is highly prevalent among older adults, particularly those in institutionalized settings, contributing to conditions such as atrophic gastritis, peptic ulcer disease, and gastric carcinoma. This review examines the intricate interplay between aging, gastrointestinal changes, and H. pylori pathogenesis. The age-associated decline in immune function, known as immunosenescence, exacerbates the challenges of managing H. pylori infection. Comorbidities and polypharmacy further increase the risk of adverse outcomes in older adults. Current clinical guidelines inadequately address the specific needs of the geriatric population, who are disproportionately affected by antibiotic resistance, heightened side effects, and diagnostic complexities. This review focuses on recent advancements in understanding H. pylori infection among older adults, including epidemiology, diagnostics, therapeutic strategies, and age-related gastric changes. Diagnostic approaches must consider the physiological changes that accompany aging, and treatment regimens need to be carefully tailored to balance efficacy and tolerability. Emerging strategies, such as novel eradication regimens and adjunctive probiotic therapies, show promise for improving treatment outcomes. However, significant knowledge gaps persist regarding the impact of aging on H. pylori pathogenesis and treatment efficacy. A multidisciplinary approach involving gastroenterologists, geriatricians, and other specialists is crucial to providing comprehensive care for this vulnerable population. Future research should focus on refining diagnostic and therapeutic protocols to bridge these gaps, ultimately enhancing clinical outcomes and reducing the burden of H. pylori-associated diseases in the aging population.
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Affiliation(s)
- Jaroslaw Skokowski
- Department of Medicine, Academy of Applied Medical and Social Sciences-AMiSNS: Akademia Medycznych I Spolecznych Nauk Stosowanych, 82-330 Elbląg, Poland;
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, 80-000 Gdańsk, Poland; (S.G.); (T.C.); (P.M.)
| | - Yogesh Vashist
- Organ Transplant Center for Excellence, Center for Liver Diseases and Oncology, King Faisal Specialist Hospital and Research Center, 12211 Riyadh, Saudi Arabia; (Y.V.); (M.A.A.)
| | - Sergii Girnyi
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, 80-000 Gdańsk, Poland; (S.G.); (T.C.); (P.M.)
| | - Tomasz Cwalinski
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, 80-000 Gdańsk, Poland; (S.G.); (T.C.); (P.M.)
| | - Piotr Mocarski
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, 80-000 Gdańsk, Poland; (S.G.); (T.C.); (P.M.)
| | - Carmine Antropoli
- Department of Surgery, Antonio Cardarelli Hospital, 80100 Naples, Italy; (C.A.); (A.B.)
| | - Antonio Brillantino
- Department of Surgery, Antonio Cardarelli Hospital, 80100 Naples, Italy; (C.A.); (A.B.)
| | - Virginia Boccardi
- Division of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy;
| | - Aman Goyal
- Adesh Institute of Medical Sciences and Research, 151001 Bathinda, Punjab, India;
| | - Francesco A. Ciarleglio
- Department of General Surgery and Hepato-Pancreato-Biliary (HPB) Unit-APSS, 38121Trento, Italy;
| | - Muhannad Abdullah Almohaimeed
- Organ Transplant Center for Excellence, Center for Liver Diseases and Oncology, King Faisal Specialist Hospital and Research Center, 12211 Riyadh, Saudi Arabia; (Y.V.); (M.A.A.)
| | - Raffaele De Luca
- Department of Surgical Oncology, IRCCS Istituto Tumori “Giovanni Paolo II”, 70100 Bari, Italy;
| | - Adel Abou-Mrad
- Department of Surgery, Centre Hospitalier Universitaire d’Orléans, 45100 Orléans, France;
| | - Luigi Marano
- Department of Medicine, Academy of Applied Medical and Social Sciences-AMiSNS: Akademia Medycznych I Spolecznych Nauk Stosowanych, 82-330 Elbląg, Poland;
- Department of General Surgery and Surgical Oncology, “Saint Wojciech” Hospital, “Nicolaus Copernicus” Health Center, 80-000 Gdańsk, Poland; (S.G.); (T.C.); (P.M.)
- Department of Medicine, Surgery, and Neurosciences, University of Siena, 53100 Siena, Italy
| | - Rodolfo J. Oviedo
- Department of Surgery, Nacogdoches Medical Center, Nacogdoches, TX 75965, USA;
- Department of Surgery, University of Houston Tilman J. Fertitta Family College of Medicine, Houston, TX 75961, USA
- Department of Surgery, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77301, USA
| | - Beata Januszko-Giergielewicz
- Department of Medicine, Academy of Applied Medical and Social Sciences-AMiSNS: Akademia Medycznych I Spolecznych Nauk Stosowanych, 82-330 Elbląg, Poland;
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Said ZNA, El-Nasser AM. Evaluation of urea breath test as a diagnostic tool for Helicobacter pylori infection in adult dyspeptic patients. World J Gastroenterol 2024; 30:2302-2307. [PMID: 38813047 PMCID: PMC11130578 DOI: 10.3748/wjg.v30.i17.2302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 03/09/2024] [Accepted: 04/15/2024] [Indexed: 04/30/2024] Open
Abstract
In this editorial, we discuss the article in the World Journal of Gastroenterology. The article conducts a meta-analysis of the diagnostic accuracy of the urea breath test (UBT), a non-invasive method for detecting Helicobacter pylori (H. pylori) infection in humans. It is based on radionuclide-labeled urea. Various methods, both invasive and non-invasive, are available for diagnosing H. pylori infection, including endoscopy with biopsy, serology for immunoglobulin titers, stool antigen analysis, and UBT. Several guidelines recommend UBTs as the primary choice for diagnosing H. pylori infection and for reexamining after eradication therapy. It is used to be the first choice non-invasive test due to their high accuracy, specificity, rapid results, and simplicity. Moreover, its performance remains unaffected by the distribution of H. pylori in the stomach, allowing a high flow of patients to be tested. Despite its widespread use, the performance characteristics of UBT have been inconsistently described and remain incompletely defined. There are two UBTs available with Food and Drug Administration approval: The 13C and 14C tests. Both tests are affordable and can provide real-time results. Physicians may prefer the 13C test because it is non-radioactive, compared to 14C which uses a radioactive isotope, especially in young children and pregnant women. Although there was heterogeneity among the studies regarding the diagnostic accuracy of both UBTs, 13C-UBT consistently outperforms the 14C-UBT. This makes the 13C-UBT the preferred diagnostic approach. Furthermore, the provided findings of the meta-analysis emphasize the significance of precise considerations when choosing urea dosage, assessment timing, and measurement techniques for both the 13C-UBT and 14C-UBT, to enhance diagnostic precision.
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Affiliation(s)
- Zeinab Nabil Ahmed Said
- Department of Medical Microbiology & Immunology, Faculty of Medicine for Girls Al-Azhar University, Nasr City 11754, Cairo, Egypt
| | - Asmaa Mohamed El-Nasser
- Department of Medical Microbiology & Immunology, Faculty of Medicine for Girls Al-Azhar University, Nasr City 11754, Cairo, Egypt
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Omar M, Abu-Salah R, Agbareia R, Sharif Y, Levin R, Lahat A, Sharif K. A comparative systematic review and meta-analysis on the diagnostic accuracy of non-invasive tests for Helicobacter pylori detection in elderly patients. Front Med (Lausanne) 2023; 10:1323113. [PMID: 38143438 PMCID: PMC10748425 DOI: 10.3389/fmed.2023.1323113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 11/23/2023] [Indexed: 12/26/2023] Open
Abstract
Background Helicobacter pylori (H. pylori) infection, a type I carcinogen, affects approximately 50% of the global population, correlating with various gastric pathologies. Notably, diagnostic sensitivities of non-invasive methods, such as the stool antigen test (HpSA), Serology, and Urea Breath Test (UBT), have been suggested to be less effective in older age groups. This study systematically reviews and meta-analyzes the diagnostic accuracy of these tests within the elderly population. Methods A comprehensive literature search was performed across multiple databases, including PubMed, Medline, and Web of Science, up to July 2023. Data were pooled and analyzed using random-effects models. Sensitivity, specificity, and Diagnostic Odds Ratios (DOR) were computed for the tests. Heterogeneity and risk of bias were assessed. Results Eight studies involving diverse geographic locations and totaling between 46 and 1,441 participants per study were included. The pooled sensitivity and specificity for HpSA were 72.5 and 94.7%, for Serology 83.7 and 73.3%, and for UBT 96.4 and 88.3%, respectively. DOR for UBT, HpSA, and Serology were 94.5, 47.9, and 14.2, respectively. High levels of heterogeneity were observed across the studies. Conclusion UBT and HpSA proved effective for diagnosing H. pylori in those over 60, while serology showed lower specificity. Despite methodological variations in available studies, these non-invasive tests offer reliable alternatives, especially for older patients who recently undergone endoscopy or without an indication for it, warranting consideration by healthcare practitioners.
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Affiliation(s)
- Mahmud Omar
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Razi Abu-Salah
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | | | - Yusra Sharif
- Hebrew University Medical School, Jerusalem, Israel
- Department of Medicine C, Hadassah Medical Centre, Jerusalem, Israel
| | - Roni Levin
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Medicine B, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel
| | - Adi Lahat
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel
| | - Kassem Sharif
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel
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Ma TL, Tai WC, Loke SS, Yao CC, Liang CM, Chuah SK. Efficacy and Safety of 7-Day Non-Bismuth Concomitant Quadruple Therapy for First-Line Helicobacter pylori Eradication in the Elderly. Drugs Aging 2023; 40:71-79. [PMID: 36602725 DOI: 10.1007/s40266-022-00990-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/15/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND Aging may affect the efficacy of Helicobacter pylori eradication. The aim of our study was to assess the efficacy and safety of 7-day non-bismuth concomitant quadruple therapy as a first-line H. pylori infection eradication regimen in elderly individuals. METHODS We retrospectively analyzed a cohort with prospectively collected data from January 2013 to December 2019 at Chang Gung Memorial Hospital in Kaohsiung. There were 408 naive infected subjects aged 20 years or older who were treated with 7 days of concomitant therapy as a first-line H. pylori eradication regimen. We divided the patients into an elderly group (aged ≥ 65 years) and a control group (aged < 65 years). Two patients were lost during follow-up in the elderly group and 29 patients were lost in the control group, resulting in 56 in the ≥ 65-year age group and 321 in the control group. The patients were asked to perform urea breath tests 8 weeks later. RESULTS The eradication rates for the elderly and control groups were 93.1% (95% confidence interval (CI): 83.3-98.1) and 84.0% (95% CI 79.7-87.7) (p = 0.070), respectively, in the intention-to-treat analysis, and 96.4% (95% CI 87.6-99.6) and 91.6% (95% CI 88.0-94.4) (p = 0.210), respectively, in the per-protocol (PP) analysis. The adverse event rates were 8.9% in the elderly group and 12.8% in the control group (p = 0.417). The compliance was 100% in both groups. No significant difference was seen in antibiotic resistance in either group. Multivariate analysis revealed that metronidazole resistance (odds ratio (OR) 6.870, 95% CI 1.182-39.919, p = 0.032) and dual-therapy resistance (OR 7.188, 95% CI 1.326-38.952, p = 0.022) were independent factors for eradication failure. CONCLUSIONS The efficacy of non-bismuth concomitant quadruple therapy in the elderly cohort was comparable with that in the non-elderly cohort for first-line H. pylori eradication with acceptable adverse effects.
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Affiliation(s)
- Te-Ling Ma
- Department of Internal Medicine, Fu Jen Catholic University Hospital, New Taipei City, Taipei, Taiwan
| | - Wei-Chen Tai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Niao-Sung Dist. 833, Kaohsiung City, Taiwan.,Chang Gung University College of Medicine, Taoyuan City, Taiwan
| | - Song-Seng Loke
- Division of Family Physician, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Chien Yao
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Niao-Sung Dist. 833, Kaohsiung City, Taiwan
| | - Chih-Ming Liang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Niao-Sung Dist. 833, Kaohsiung City, Taiwan. .,Chang Gung University College of Medicine, Taoyuan City, Taiwan.
| | - Seng-Kee Chuah
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Niao-Sung Dist. 833, Kaohsiung City, Taiwan.,Chang Gung University College of Medicine, Taoyuan City, Taiwan
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Huang Q, Jia X, Chu Y, Zhang X, Ye H. Helicobacter pylori Infection in Geriatric Patients: Current Situation and Treatment Regimens. Front Med (Lausanne) 2021; 8:713908. [PMID: 34660627 PMCID: PMC8514670 DOI: 10.3389/fmed.2021.713908] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Accepted: 09/03/2021] [Indexed: 12/24/2022] Open
Abstract
Helicobacter pylori (H. pylori) has so far infected more than half the global population. It is the most important and controllable risk factor for gastric cancer. The elderly, who are at a higher incidence of the infection, are also commonly found to develop antibiotic resistance. The symptoms, diagnosis, clinical features (of gastric or extra-digestive diseases), and treatment of H. pylori infection in the elderly, are different from that in the non-elderly. Health conditions, including comorbidities and combined medication have limited the use of regular therapies in elderly patients. However, they can still benefit from eradication therapy, thus preventing gastric mucosal lesions and gastric cancer. In addition, new approaches, such as dual therapy and complementary therapy, have the potential to treat older patients with H. pylori infection.
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Affiliation(s)
| | | | | | - Xuezhi Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Beijing, China
| | - Hui Ye
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Beijing, China
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Sabbagh P, Mohammadnia-Afrouzi M, Javanian M, Babazadeh A, Koppolu V, Vasigala VR, Nouri HR, Ebrahimpour S. Diagnostic methods for Helicobacter pylori infection: ideals, options, and limitations. Eur J Clin Microbiol Infect Dis 2019; 38:55-66. [PMID: 30414090 DOI: 10.1007/s10096-018-3414-4] [Citation(s) in RCA: 94] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Accepted: 10/26/2018] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori (H. pylori) resides in the stomach, colonizes gastric epithelium, and causes several digestive system diseases. Several diagnostic methods utilizing invasive or non-invasive techniques with varying levels of sensitivity and specificity are developed to detect H. pylori infection. Selection of one or more diagnostic tests will depend on the clinical conditions, the experience of the clinician, cost, sensitivity, and specificity. Invasive methods require endoscopy with biopsies of gastric tissues for the histology, culture, and rapid urease test. Among non-invasive tests, urea breath test and fecal antigen tests are a quick diagnostic procedure with comparable accuracy to biopsy-based techniques and are methods of choice in the test and treatment setting. Other techniques such as serological methods to detect immunoglobulin G antibodies to H. pylori can show high accuracy as other non-invasive and invasive biopsies, but do not differentiate between current or past H. pylori infections. Polymerase chain reaction (PCR) is an emerging option that can be categorized as invasive and non-invasive tests. PCR method is beneficial to detect H. pylori from gastric biopsies without the need for the cultures. There is no other chronic gastrointestinal infection such as H. pylori with a set of comparable diagnostic methodologies. Despite the availability of multiple diagnostic methods, it remains unclear on the choice of any one method as the gold standard for detecting H. pylori infection, especially in epidemiological studies. In this work, we review the principal diagnostic methods used to detect H. pylori infection and their advantages and disadvantages, and applications in clinical practice.
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Affiliation(s)
- Parisa Sabbagh
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Islamic Republic of Iran
| | - Mousa Mohammadnia-Afrouzi
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Islamic Republic of Iran
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Islamic Republic of Iran
| | - Mostafa Javanian
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Islamic Republic of Iran
| | - Arefeh Babazadeh
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Islamic Republic of Iran
| | - Veerendra Koppolu
- Scientist Biopharmaceutical Development Medimmune, Gaithersburg, MD, 20878, USA
| | | | - Hamid Reza Nouri
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Islamic Republic of Iran
| | - Soheil Ebrahimpour
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Islamic Republic of Iran.
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Leal YA, Flores LL, García-Cortés LB, Cedillo-Rivera R, Torres J. Antibody-based detection tests for the diagnosis of Helicobacter pylori infection in children: a meta-analysis. PLoS One 2008; 3:e3751. [PMID: 19015732 PMCID: PMC2582133 DOI: 10.1371/journal.pone.0003751] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2008] [Accepted: 10/26/2008] [Indexed: 01/11/2023] Open
Abstract
Background Numerous serologic tests are available for the diagnosis of H. pylori infection in children. Common designs of antibody-based detection tests are ELISA and Western Blot (WB). For developing countries with limited laboratory resources and access, ELISA would be the preferred method because of its simplicity, lower cost and speed. Although in adults ELISA has proven to be highly accurate in diagnosing H. pylori infection; in children, it has shown variable accuracy. Methods/Findings We conducted a systematic review and meta-analysis to assess the accuracy of antibody-based detection tests for the diagnosis of H. pylori infection in children. Selection criteria included participation of at least 30 children and the use of a gold standard for H. pylori diagnosis. In a comprehensive search we identified 68 studies. Subgroup analyses were carried out by technique, immunoglobulin class, and source of test (commercial and in-house). The results demonstrated: 1) WB tests showed high overall performance, sensitivity 91.3% (95% CI, 88.9–93.3), specificity 89% (95% CI, 85.7–91.9), LR+ 8.2 (95% CI, 5.1–13.3), LR− 0.06 (95% CI, 0.02–0.16), DOR 158.8 (95% CI, 57.8–435.8); 2) ELISA-IgG assays showed low sensitivity 79.2% (95% CI, 77.3–81.0) and high specificity (92.4%, 95% CI, 91.6–93.3); 3) ELISA commercial tests varied widely in performance (test for heterogeneity p<0.0001); and 4) In-house ELISA with whole-cell antigen tests showed the highest overall performance: sensitivity 94% (95% CI, 90.2–96.7), specificity 96.4% (95% CI, 94.2–97.9), LR+ 19.9 (95% CI, 7.9–49.8), LR− 0.08 (95% CI, 0.04–0.15) DOR 292.8 (95% CI, 101.8–841.7). Conclusions/Significance WB test and in-house ELISA with whole-cell antigen tests are the most reliable tests for the diagnosis of H. pylori infection in children. Antigens obtained from local strains of the community could partially explain the good overall accuracy of the in-house ELISA. Because of its cost and technical demands, in-house ELISA might be more suitable for use in developing countries.
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Affiliation(s)
- Yelda A Leal
- Unidad de Investigación Médica Yucatán (UIMY), Unidad Médica de Alta Especialidad de Mérida, Instituto Mexicano del Seguro Social, Mérida, Yucatán, México.
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Mégraud F, Lehours P. Helicobacter pylori detection and antimicrobial susceptibility testing. Clin Microbiol Rev 2007; 20:280-322. [PMID: 17428887 PMCID: PMC1865594 DOI: 10.1128/cmr.00033-06] [Citation(s) in RCA: 486] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The discovery of Helicobacter pylori in 1982 was the starting point of a revolution concerning the concepts and management of gastroduodenal diseases. It is now well accepted that the most common stomach disease, peptic ulcer disease, is an infectious disease, and all consensus conferences agree that the causative agent, H. pylori, must be treated with antibiotics. Furthermore, the concept emerged that this bacterium could be the trigger of various malignant diseases of the stomach, and it is now a model for chronic bacterial infections causing cancer. Most of the many different techniques involved in diagnosis of H. pylori infection are performed in clinical microbiology laboratories. The aim of this article is to review the current status of these methods and their application, highlighting the important progress which has been made in the past decade. Both invasive and noninvasive techniques will be reviewed.
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Affiliation(s)
- Francis Mégraud
- INSERM U853, and Université Victor Segalen Bordeaux 2, and Laboratoire de Bactériologie, Hôpital Pellegrin, Place Amélie Raba-Léon, 33076 Bordeaux cedex, France.
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Mangia A, Chiriatti A, Ranieri G, Abbate I, Coviello M, Simone G, Zito FA, Montemurro S, Rucci A, Di Leo A, Tommasi S, Berloco P, Xu JM, Paradiso A. H pylori status and angiogenesis factors in human gastric carcinoma. World J Gastroenterol 2006; 12:5465-72. [PMID: 17006982 PMCID: PMC4088227 DOI: 10.3748/wjg.v12.i34.5465] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate H pylori expression in gastric cancer patients in relation to primary tumor angiogenic markers, such as microvessel density (MVD), thymidine phosphorylase (TP), vascular endothelial growth factor receptor-1 (VEGF-R1), p53 and circulating VEGF levels.
METHODS: Angiogenic markers were analyzed immunohistochemically in 56 primary gastric cancers. H pylori cytotoxin (vacA) and the cytotoxin-associated gene (cagA) amplification were evaluated using PCR assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels were detected in 39 and 38 patients by ELISA, respectively.
RESULTS: A total of 69% of patients were positive for circulating IgG antibodies against H pylori. cagA-positive H pylori strains were found in 41% of gastric patients. vacA was found in 50% of patients; s1 strains were more highly expressed among vacA-positive patients. The presence of the s1 strain was significantly associated with cagA (P = 0.0001). MVD was significantly correlated with both tumor VEGF expression (r = 0.361, P = 0.009) and serum VEGF levels (r = -0.347, P = 0.041). Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression. However, H pylori was not related to any angiogenic markers except for the plasma VEGF level (P = 0.026).
CONCLUSION: H pylori antigen is related to higher plasma VEGF levels, but not to angiogenic characteristics. It can be hypothesized that the toxic effects of H pylori on angiogenesis occurs in early preclinical disease phase or in long-lasting aggressive infections, but only when high H pylori IgG levels are persistent.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Antigens, Bacterial/genetics
- Antigens, Bacterial/metabolism
- Bacterial Proteins/genetics
- Bacterial Proteins/metabolism
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Female
- Gene Expression Regulation, Bacterial
- Gene Expression Regulation, Neoplastic
- Helicobacter Infections/complications
- Helicobacter Infections/genetics
- Helicobacter Infections/metabolism
- Helicobacter pylori/genetics
- Helicobacter pylori/immunology
- Helicobacter pylori/pathogenicity
- Humans
- Immunoglobulin G/blood
- Immunoglobulin G/genetics
- Male
- Microcirculation
- Middle Aged
- Neovascularization, Pathologic/genetics
- Neovascularization, Pathologic/metabolism
- Neovascularization, Pathologic/physiopathology
- Receptors, Vascular Endothelial Growth Factor/genetics
- Receptors, Vascular Endothelial Growth Factor/metabolism
- Stomach Neoplasms/blood supply
- Stomach Neoplasms/genetics
- Stomach Neoplasms/metabolism
- Stomach Neoplasms/microbiology
- Thymidine Phosphorylase/genetics
- Thymidine Phosphorylase/metabolism
- Tumor Suppressor Protein p53/genetics
- Tumor Suppressor Protein p53/metabolism
- Vascular Endothelial Growth Factor A/blood
- Vascular Endothelial Growth Factor A/metabolism
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Affiliation(s)
- Anita Mangia
- Clinical Experimental Oncology Laboratory, National Cancer Institute, Via Amendola 209, Bari 70126, Italy
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Kullavanijaya P, Thong-Ngam D, Hanvivatvong O, Nunthapisud P, Tangkijvanich P, Suwanagool P. Analysis of eight different methods for the detection of Helicobacter pylori infection in patients with dyspepsia. J Gastroenterol Hepatol 2004; 19:1392-6. [PMID: 15610313 DOI: 10.1111/j.1440-1746.2004.03506.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND The present study was designed to compare the accuracy of eight different methods for the detection of Helicobacter pylori (H. pylori) infection in patients with dyspepsia. These tests included culture, histology, rapid urease test (CLO test), serology, saliva IgA, gastric juice IgA, and two in-house methods, namely in-house urease test and Gram stain. METHODS H. pylori infection was diagnosed prospectively in 200 untreated patients who underwent upper gastrointestinal endoscopy at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between July 1999 and August 2001. The gold standard for H. pylori infection was based on a positive culture or both a positive histological examination and CLO test. RESULTS The culture provided a sensitivity of 55.9% whereas saliva IgA and gastric juice IgA had a sensitivity of 26.8% and 22.2%, respectively. In contrast, the other tests provided satisfactory sensitivities ranging between 89.3% and 100% (Gram stain 89.3%, histology 93.5%, serology 96.8%, CLO test 99.0%, in-house urease test 100%). The specificities of the tests ranged between 75% and 100% (culture 100%, CLO test 91.9%, histology 90.4%, in-house urease test 88.9%, Gram stain 93.5% serology 96.8%, gastric juice IgA 91.7% and saliva IgA 75%). CONCLUSIONS Majority of invasive and non-invasive tests in this study were accurate for the diagnosis of H. pylori infection. However, the secretory IgA-based techniques in saliva and gastric juice seem to be inappropriate for determining H. pylori status in our populations due to their low sensitivities.
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Affiliation(s)
- Pinit Kullavanijaya
- Gastroenterology Unit, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University Hospital, Bangkok, Thailand
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11
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Monteiro L, de Mascarel A, Sarrasqueta AM, Bergey B, Barberis C, Talby P, Roux D, Shouler L, Goldfain D, Lamouliatte H, Mégraud F. Diagnosis of Helicobacter pylori infection: noninvasive methods compared to invasive methods and evaluation of two new tests. Am J Gastroenterol 2001; 96:353-8. [PMID: 11232675 DOI: 10.1111/j.1572-0241.2001.03518.x] [Citation(s) in RCA: 126] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Current guidelines recommending Helicobacter pylori eradication treatment without performing endoscopy in certain patients highlight the importance of noninvasive tests. Our aim was to determine the accuracy of two new tests: the antigen stool test and Helicoblot 2.1 (an immunoblot used on serum) as well as the 13C urea breath test and ELISA serology in comparison to invasive tests for the pretreatment diagnosis of H. pylori infection. METHODS Helicobacter pylori infection was diagnosed prospectively in 104 untreated patients using eight different tests. Invasive tests included culture, urease test (CLOtest), histology, and PCR; noninvasive tests included the 13C urea breath test, IgG serology (Pyloriset EIA-G), immunoblot (Helicoblot 2.1), and antigen stool detection (Premier Platinum HpSA). A predefined gold standard based on biopsy tests was used to define H. pylori status, as well as an empirical approach. RESULTS There was no statistically significant difference between the different tests. The sensitivity of the noninvasive tests ranged between 88.9% and 95.6% (stool test: 88.9%, 95% CI: 82.7-95.1, and Helicoblot 2.1: 95.6%, 95% CI: 91.5-99.6) and the specificity ranged between 92.6 and 98.1% (stool test: 94.4%, 95% CI: 84.6-98.8, and Helicoblot 2.1: 92.6%, 95% CI: 91.5-96.2) when a predefined gold standard was used. CONCLUSIONS Most tests had sensitivities, specificities, and predictive values >90%. The noninvasive tests are accurate for the diagnosis of H. pylori infection. Helicoblot 2.1 performed as well as the best ELISA kit. The HpSA is a promising direct noninvasive test that can be applied easily to evaluate H. pylori status.
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Affiliation(s)
- L Monteiro
- Laboratoire de Bactériologie, Université Victor Segalen, Bordeaux 2, France
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12
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Vaira D, Holton J, Menegatti M, Ricci C, Landi F, Ali' A, Gatta L, Acciardi C, Farinelli S, Crosatti M, Berardi S, Miglioli M. New immunological assays for the diagnosis of Helicobacter pylori infection. Gut 1999; 45 Suppl 1:I23-7. [PMID: 10457032 PMCID: PMC1766658 DOI: 10.1136/gut.45.2008.i23] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Abstract
There are several types of immunological tests available for the diagnosis and management of Helicobacter pylori infection. Most commercially available serological kits use the enzyme linked immunosorbent assay (ELISA) test format. Originally the kits used crude antigen preparations although many of the newer kits use a more purified antigen preparation, with often increased specificity but lower sensitivity. Near patient test kits are based either on latex agglutination or immunochromatography. Generally they have low sensitivities compared with laboratory tests. Western blotting, ELISA, and recombinant immunoblot assays (RIBA) have also been developed into commercially available kits and can be used to indicate the presence of specific virulence markers. An antigen detection kit has been developed for the detection of Helicobacter pylori in faeces. Immunological reagents have also been combined with other diagnostic modalities to develop immunohistochemical stains and DNA immunoassays. Helicobacter pylori is now recognised as the cause of gastritis and most cases of peptic ulcer disease (PUD); its long term carriage increases the risk of gastric adenocarcinoma sixfold and it is designated as a class I carcinogen. H pylori has also been implicated as a cause of gastric mucosa associated lymphoid tissue lymphomas. Its relation to non-ulcer dyspepsia remains controversial. Additionally, long term carriage of the organism may be associated with short stature in young girls and, in the general population, as a possible risk factor for the development of vasospastic disorders and possibly skin immunopathology such as urticaria. With the recognition of H pylori as an important human pathogen, it has become one of the growing number of organisms to have its complete genome sequence mapped. Serology is an important method of determining colonisation status and can be used for diagnosis, as a screening procedure, or to follow the efficacy of eradication regimens. Most serological assays are in the ELISA format although some are based on the latex agglutination reaction. These latter are used principally as near patient assays. Most assays detect IgG in serum although some detect serum IgA. More recently developed assays detect IgA in saliva and the production of affinity purified antibodies has led to the development of an antigen detection assay for faecal specimens. Serological reagents have also been used in immunocytochemistry and to speed up the detection of amplified products of the polymerase chain reaction (PCR)-DNA immunoassays.
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Affiliation(s)
- D Vaira
- Department of Internal Medicine, University of Bologna, Bologna, Italy
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13
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Laheij RJ, Straatman H, Jansen JB, Verbeek AL. Evaluation of commercially available Helicobacter pylori serology kits: a review. J Clin Microbiol 1998; 36:2803-9. [PMID: 9738024 PMCID: PMC105068 DOI: 10.1128/jcm.36.10.2803-2809.1998] [Citation(s) in RCA: 88] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Affiliation(s)
- R J Laheij
- Department of Gastroenterology, University Hospital Nijmegen, Nijmegen, The Netherlands.
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14
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Vaira D, Holton J, Menegatti M, Landi F, Ricci C, Ali A, Gatta L, Farinelli S, Acciardi C, Massardi B, Miglioli M. Blood tests in the management of Helicobacter pylori infection. Italian Helicobacter pylori Study Group. Gut 1998; 43 Suppl 1:S39-46. [PMID: 9764039 PMCID: PMC1766597 DOI: 10.1136/gut.43.2008.s39] [Citation(s) in RCA: 25] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
There are three main types of blood test available for the management of Helicobacter pylori infection: those that detect an antibody response; tests of the pathophysiological state of the stomach; and those that indicate an active infection. Enzyme linked immunosorbent assay (ELISA) based kits are the most numerous of the commercially available tests. Originally the kits used crude antigen preparations but many of the newer kits use a more purified antigen preparation giving increased specificity but a lower sensitivity. The sensitivity, specificity, and predictive values of the tests can also be affected by the population under test and coexistent disease in the patients. Near patient test kits are based on either latex agglutination or immunochromatography. Generally, they have low sensitivities compared with laboratory tests. Commercial western blotting kits have also been developed and are used to detect the presence of specific virulence markers. The exact role of serology in the management of Helicobacter infection has still to be defined, although there is evidence that, used as a screening procedure, it can reduce endoscopy cost and workload. Gastrin and pepsinogen blood concentrations may provide valuable information on the pathophysiological state of the stomach--for example, the presence of inflammation or gastric atrophy. A combination of serology and serum concentrations of gastrin and pepsinogen may be used effectively to detect serious gastroduodenal disease in patients.
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Affiliation(s)
- D Vaira
- Department of Internal Medicine, University of Bologna, Italy
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Misawa K, Kumagai T, Shimizu T, Furihata K, Ota H, Akamatsu T, Katsuyama T. A new histological procedure for re-evaluation of the serological test for Helicobacter pylori. Eur J Clin Microbiol Infect Dis 1998; 17:14-9. [PMID: 9512176 DOI: 10.1007/bf01584357] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
To re-evaluate the accuracy of the serological test for Helicobacter pylori, fixation of biopsy specimens with Carnoy's solution (preserving the mucous layer in tissue preparations) followed by immunohistochemical staining (a new histological procedure) was used as the reference histological method instead of 10% formalin fixation followed by hematoxylin-eosin staining (the conventional histological procedure). Biopsy specimens (antrum and body) from 114 patients with gastritis (including non-ulcer dyspepsia) or gastric and/or duodenal ulcers were obtained by endoscopy and used for both bacteriological culture and histological examination. Serum samples were taken from all patients at the time of endoscopy. The serum levels of specific IgG and IgA antibodies for Helicobacter pylori were measured by commercial enzyme immunoassay kits. The reliability of the IgG and IgA measurements was evaluated by analyzing receiver operating characteristic curves obtained using the two histological procedures. With the conventional histological procedure as the reference, the sensitivity and specificity levels of the serological test were 87.2% and 82.1%, respectively. With the new histological procedure as reference, sensitivity and specificity were 94% and 96.7%, respectively. The insufficient accuracy reported for the serological test could be due to false-positive or false-negative results obtained when the conventional histological procedure is used as the reference. The new histological procedure used here revealed that the serological test for Helicobacter pylori is more reliable than previously thought.
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Affiliation(s)
- K Misawa
- Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan
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16
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Nakao K, Imoto I, Gabazza EC, Yamauchi K, Yamazaki N, Taguchi Y, Shibata T, Takaji S, Ikemura N, Misaki M. Gastric juice levels of lactoferrin and Helicobacter pylori infection. Scand J Gastroenterol 1997; 32:530-4. [PMID: 9200282 DOI: 10.3109/00365529709025094] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Recently, in vitro studies suggested that lactoferrin (Lf) might play an important role in the physiopathology of Helicobacter pylori-associated gastritis. However, whether Lf is present in the gastric juice and its relationship with H. pylori infection have not as yet been reported. In the present investigation the presence of Lf in gastric juice and its correlation with H. pylori infection were assessed. METHODS This study comprised 30 H. pylori-positive and 14-negative patients with chronic gastritis. Gastric juice levels of Lf were measured with enzyme-linked immunoassays. Gastric juice concentration of Lf was also investigated in accordance with the histologic findings of biopsy specimens in the gastric body and antrum. RESULTS Lf concentration in gastric juice was significantly higher in H. pylori-positive than in -negative patients (P = 0.033). The pH values are known to influence the levels of Lf. However, intragastric Lf levels were also significantly increased in H. pylori-positive patients as compared with H. pylori-negative patients after correcting the Lf levels for pH values (P = 0.029) or after adjusting the pH values of the gastric juice with NaHCO3 solution in both groups of patients (P = 0.0007). In addition, the gastric juice levels of Lf correlated significantly with the gastric mucosal concentrations of Lf in the gastric body (P < 0.005, r = 0.568) and the antrum (P < 0.05, r = 0.401). CONCLUSIONS This study showed for the first time that Lf is present in gastric juice and that it correlates with H. pylori infection. Lf may constitute a good marker for H. pylori-associated gastritis. Although correlation does not prove causation, this study suggests that Lf might play an important role in the physiopathology of H. pylori-associated gastritis.
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Affiliation(s)
- K Nakao
- Third Dept. of Internal Medicine, Mie University School of Medicine, Tsu, Japan
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Pilotto A, Franceschi M, Leandro G, DiMario F, Soffiati G, Scagnelli M, Bozzola L, Fabrello R, Valerio G. The clinical usefulness of serum pepsinogens, specific IgG anti-HP antibodies and gastrin for monitoring Helicobacter pylori treatment in older people. J Am Geriatr Soc 1996; 44:665-670. [PMID: 8642157 DOI: 10.1111/j.1532-5415.1996.tb01829.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
OBJECTIVE To evaluate the clinical usefulness of Pepsinogen A (PGA) and C (PGC), PGA/PGC ratio, gastrin, and specific IgG anti-HP antibodies (anti-HP Ab) in monitoring the effect of cure for Helicobacter pylori (HP) infection in older people. DESIGN We studied the changes in serum parameters (PGA, PGC, PGA/PGC ratio, gastrin and anti-HP Ab) in older patients before and 2 months after stopping therapy for the cure of HP infection. PATIENTS Eighty-eight older patients (M = 43, F = 45, mean age = 73.3, range = 60-89) with chronic gastritis (42), gastric ulcer (14) or duodenal ulcer (32) were found HP-positive by histology of gastric antral and body biopsies and the rapid urease test. INTERVENTIONS Two different associations of antibiotics and antiulcer drugs (omeprazole, metronidazole, azithromycin, or clarithromycin) for 2-4 weeks. MEASUREMENTS At the beginning of the study and 2 months after treatment withdrawal, the subjects were studied by upper G.I. endoscopy with at least two antral and two body gastric biopsies (Giemsa stain and rapid urease test for HP); serum PGA (RIA method, microgram/mL), PGC (RIA method, microgram/mL), PGA/PGC ratio, gastrin (RIA method, picogr/mL), and anti-HP Ab (ELISA method, Biolife, MU/mL) were also determined. Statistical analysis was based on either the Wilcoxon test, for paired data, the chi-square test, the Kruskal Wallis test, or the Mann-Whitney test for unpaired data. The choice of the best cut-off value in the different parameters was performed by receiver operating characteristics curves (ROC) and by Youden index. The correlation between HP density in the gastric mucosa and gastritis activity was verified by Spearman rank correlation test. RESULTS After therapy, 56/88 patients proved HP-negative (HP-eradicated: M = 30, F = 26, mean age = 73.0, range = 60-87 years), whereas 32/88 were not cured (HP-persistent: M = 13, F = 19, mean age = 73.0, range = 60-89 years). After therapy, in HP-eradicated cases, a statistically significant change was found in anti-HP Ab (75.23 +/- 8.94 vs 47.32 +/- 5.26, P < .001), PGC (21.58 +/- 1.97 vs 14.34 +/- 1.75, P < .001), and PGA/PGC ratio (8.46 +/- 0.68 vs 11.54 +/- 0.89, P < .001), but not in PGA and gastrin. On the other hand, in HP-persistent cases, anti-HP Ab, PGA, PGC, PGA/ PGC ratio and gastrin did not change after therapy. The sensitivity and specificity were, respectively, 0.62 and 0.56 for anti-HP Ab and 0.75 and 0.56 for the PGA/PGC ratio, which demonstrated the best diagnostic accuracy (68%). CONCLUSIONS The eradication of HP from the stomach of older patients induces a rapid and significant decrease in serum levels of IgG anti-HP antibodies and PGC, with an increase in PGA/PGC ratio but not in gastrin. Unchanged serum levels of IgG anti-HP antibodies, PGC, and PGA/PGC ratio 2 months after completing HP eradication therapy are indicative of ongoing HP infection. The PGA/PGC ratio showed the best diagnostic accuracy among serum measures tested.
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Affiliation(s)
- A Pilotto
- Division of Geriatric Medicine, S.Bortolo Hospital, Vicenza, Italy
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Bateson MC. Gastroenterology--I: Gastroduodenal disease and Helicobacter pylori. Postgrad Med J 1994; 70:561-7. [PMID: 7937449 PMCID: PMC2397689 DOI: 10.1136/pgmj.70.826.561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Affiliation(s)
- M C Bateson
- General Hospital, Bishop Auckland, Co. Durham, UK
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