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Lemos FFB, Castro CTD, Silva Luz M, Rocha GR, Correa Santos GL, de Oliveira Silva LG, Calmon MS, Souza CL, Zarpelon-Schutz AC, Teixeira KN, Queiroz DMDM, Freire de Melo F. Urea breath test for Helicobacter pylori infection in adult dyspeptic patients: A meta-analysis of diagnostic test accuracy. World J Gastroenterol 2024; 30:579-598. [PMID: 38463019 PMCID: PMC10921142 DOI: 10.3748/wjg.v30.i6.579] [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: 11/14/2023] [Revised: 12/16/2023] [Accepted: 01/16/2024] [Indexed: 02/05/2024] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection has been well-established as a significant risk factor for several gastrointestinal disorders. The urea breath test (UBT) has emerged as a leading non-invasive method for detecting H. pylori. Despite numerous studies confirming its substantial accuracy, the reliability of UBT results is often compromised by inherent limitations. These findings underscore the need for a rigorous statistical synthesis to clarify and reconcile the diagnostic accuracy of the UBT for the diagnosis of H. pylori infection. AIM To determine and compare the diagnostic accuracy of 13C-UBT and 14C-UBT for H. pylori infection in adult patients with dyspepsia. METHODS We conducted an independent search of the PubMed/MEDLINE, EMBASE, and Cochrane Central databases until April 2022. Our search included diagnostic accuracy studies that evaluated at least one of the index tests (13C-UBT or 14C-UBT) against a reference standard. We used the QUADAS-2 tool to assess the methodological quality of the studies. We utilized the bivariate random-effects model to calculate sensitivity, specificity, positive and negative test likelihood ratios (LR+ and LR-), as well as the diagnostic odds ratio (DOR), and their 95% confidence intervals. We conducted subgroup analyses based on urea dosing, time after urea administration, and assessment technique. To investigate a possible threshold effect, we conducted Spearman correlation analysis, and we generated summary receiver operating characteristic (SROC) curves to assess heterogeneity. Finally, we visually inspected a funnel plot and used Egger's test to evaluate publication bias. RESULTS The titles and abstracts of 4621 studies were screened; 79 articles were retrieved and selected for full-text reading. Finally, 60 studies were included in the diagnostic test accuracy meta-analysis. Our analysis demonstrates superior diagnostic accuracy of 13C-UBT over 14C-UBT, indicated by higher sensitivity (96.60% vs 96.15%), specificity (96.93% vs 89.84%), likelihood ratios (LR+ 22.00 vs 10.10; LR- 0.05 vs 0.06), and area under the curve (AUC; 0.979 vs 0.968). Notably, 13C-UBT's DOR (586.47) significantly outperforms 14C-UBT (DOR 226.50), making it the preferred diagnostic tool for dyspeptic individuals with H. pylori infection. Correlation analysis revealed no threshold effect (13C-UBT: r = 0.48; 14C-UBT: r = -0.01), and SROC curves showed consistent accuracy. Both 13C-UBT and 14C-UBT showed high AUC values (13C-UBT 0.979; 14C-UBT 0.968) near 1.00, reinforcing their excellent accuracy and endorsing both as reliable diagnostic tools in clinical practice. CONCLUSION In summary, our study has demonstrated that 13C-UBT has been found to outperform the 14C-UBT, making it the preferred diagnostic approach. Additionally, our results emphasize the significance of carefully considering urea dosage, assessment timing, and measurement techniques for both tests to enhance diagnostic precision. Nevertheless, it is crucial for researchers and clinicians to evaluate the strengths and limitations of our findings before implementing them in practice.
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Affiliation(s)
- Fabian Fellipe Bueno Lemos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | | | - Marcel Silva Luz
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Gabriel Reis Rocha
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Gabriel Lima Correa Santos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | | | - Mariana Santos Calmon
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Cláudio Lima Souza
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | | | | | | | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
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Chen Q, Yang W, Gong W, Chen X, Zhu Z, Chen H. Advanced Sensing Strategies Based on Different Types of Biomarkers toward Early Diagnosis of H. pylori. Crit Rev Anal Chem 2023; 54:2277-2289. [PMID: 36598423 DOI: 10.1080/10408347.2022.2163585] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Helicobacter pylori (H. pylori) is a bacterium that can colonize human gastric epithelial cells and cause H. pylori infection, closely related to many gastric diseases. Compared with conventional H. pylori detection methods, emerging diagnostic approaches (such as biosensors) have become potentially more effective alternatives due to their high sensitivity, good selectivity and noninvasiveness. This review begins with a brief overview of H. pylori infection, the processes that lead to diseases, and current diagnostic methods. Subsequently, advanced biosensors in different target-based for diagnosing H. pylori infection are focused, including the detection of H. pylori-related nucleic acid, H. pylori-related protein (such as the cytotoxin, urease), and intact H. pylori. In addition, prospects for the development of H. pylori detection methods are also discussed in the end.
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Affiliation(s)
- Qiang Chen
- School of Medicine, Shanghai University, Shanghai, PR China
| | - Wenyi Yang
- School of Life Sciences, Shanghai University, Shanghai, PR China
| | - Weihua Gong
- Department of Oncology, Chongming Branch of Shanghai Tenth People's Hospital, Shanghai, PR China
| | - Xiaobing Chen
- Department of Oncology, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, PR China
| | - Zhongzheng Zhu
- Department of Oncology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, PR China
| | - Hongxia Chen
- School of Life Sciences, Shanghai University, Shanghai, PR China
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Pham YL, Beauchamp J. Breath Biomarkers in Diagnostic Applications. Molecules 2021; 26:molecules26185514. [PMID: 34576985 PMCID: PMC8468811 DOI: 10.3390/molecules26185514] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 09/07/2021] [Accepted: 09/08/2021] [Indexed: 02/06/2023] Open
Abstract
The detection of chemical compounds in exhaled human breath presents an opportunity to determine physiological state, diagnose disease or assess environmental exposure. Recent advancements in metabolomics research have led to improved capabilities to explore human metabolic profiles in breath. Despite some notable challenges in sampling and analysis, exhaled breath represents a desirable medium for metabolomics applications, foremost due to its non-invasive, convenient and practically limitless availability. Several breath-based tests that target either endogenous or exogenous gas-phase compounds are currently established and are in practical and/or clinical use. This review outlines the concept of breath analysis in the context of these unique tests and their applications. The respective breath biomarkers targeted in each test are discussed in relation to their physiological production in the human body and the development and implementation of the associated tests. The paper concludes with a brief insight into prospective tests and an outlook of the future direction of breath research.
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Affiliation(s)
- Y Lan Pham
- Department of Sensory Analytics and Technologies, Fraunhofer Institute for Process Engineering and Packaging IVV, Giggenhauser Straße 35, 85354 Freising, Germany;
- Department of Chemistry and Pharmacy, Chair of Aroma and Smell Research, Friedrich-Alexander-Universität Erlangen-Nürnberg, Henkestraße 9, 91054 Erlangen, Germany
| | - Jonathan Beauchamp
- Department of Sensory Analytics and Technologies, Fraunhofer Institute for Process Engineering and Packaging IVV, Giggenhauser Straße 35, 85354 Freising, Germany;
- Correspondence:
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Best LMJ, Takwoingi Y, Siddique S, Selladurai A, Gandhi A, Low B, Yaghoobi M, Gurusamy KS. Non-invasive diagnostic tests for Helicobacter pylori infection. Cochrane Database Syst Rev 2018; 3:CD012080. [PMID: 29543326 PMCID: PMC6513531 DOI: 10.1002/14651858.cd012080.pub2] [Citation(s) in RCA: 90] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori. OBJECTIVES To compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started. SEARCH METHODS We searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively. SELECTION CRITERIA We included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as 13C or 14C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection. DATA COLLECTION AND ANALYSIS Two review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities. MAIN RESULTS We included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.Of the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-13C; 21 studies (1810 participants) evaluated urea breath test-14C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.Using data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-13C, urea breath test-14C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-13C, urea breath test-14C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-13C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-14C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-13C, urea breath test-14C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).Direct comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-13C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-13C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons. AUTHORS' CONCLUSIONS In people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.We need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions.
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Affiliation(s)
- Lawrence MJ Best
- Royal Free Campus, UCL Medical SchoolDepartment of SurgeryRowland Hill StreetLondonUKNW32PF
| | - Yemisi Takwoingi
- University of BirminghamInstitute of Applied Health ResearchEdgbastonBirminghamUKB15 2TT
| | | | | | | | | | - Mohammad Yaghoobi
- McMaster University and McMaster University Health Sciences CentreDivision of Gastroenterology1200 Main Street WestHamiltonONCanada
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Perets TT, Shporn E, Boltin D, Dickman R, Niv Y. Stability of (13) C-Urea Breath Test Samples Over Time in the Diagnosis of Helicobacter pylori. J Clin Lab Anal 2015; 30:231-4. [PMID: 25600933 DOI: 10.1002/jcla.21841] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2014] [Accepted: 11/24/2014] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND The accuracy and repeatability of breath test in the diagnosis of Helicobacter pylori infection have not been adequately investigated. Although it has been shown that storage for long periods does not affect the analysis results, no data are available on the effect of repetitive testing. In this study, our aim was to evaluate the repeatability of the analyses of breath samples at room temperature. METHODS A total of 202 positive breath samples were collected in duplicates, before and after administration of 75 mg (13) C- urea dissolved in 100 ml of orange juice. Breath test results were expressed as delta (13) CO2 . The cut-off value was 3.5 parts per thousand. Each sample was analyzed in a mass spectrometer 7, 14, 21, and 28 days after collection. The accuracy calculation was based on the comparison of the delta (13) CO2 obtained in the three consecutive weeks following the first test run to the delta (13) CO2 obtained in the first test run. RESULTS Two hundred (99%), 197 (97.52%), and 196 (97%) of the 202 samples tested positive in the second, third, and fourth test runs, respectively. The accuracy of the delta (13) CO2 was 98.6%, 99.2%, and 96.7% in the three consecutive runs, respectively. CONCLUSION Short-term storage of 1 month does not affect sample stability or the results of (13) C-urea breath tests in up to three consecutive repeats.
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Affiliation(s)
- Tsachi Tsadok Perets
- Gastroenterology Laboratory, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Einav Shporn
- Gastroenterology Laboratory, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel
| | - Doron Boltin
- Department of Gastroenterology, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ram Dickman
- Department of Gastroenterology, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yaron Niv
- Department of Gastroenterology, Rabin Medical Center - Beilinson Hospital, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Abstract
Breath tests provide a valuable non-invasive diagnostic strategy to in vivo assess a variety of enzyme activities, organ functions or transport processes. Both the hydrogen breath tests and the (13)C-breath tests using the stable isotope (13)C as tracer are non-radioactive and safe, also in children and pregnancy. Hydrogen breath tests are widely used in clinical practice to explore gastrointestinal disorders. They are applied for diagnosing carbohydrate malassimilation, small intestinal bacterial overgrowth and for measuring the orocecal transit time. (13)C-breath tests non-invasively monitor the metabolisation of a (13)C-labelled substrate. Depending on the choice of the substrate they enable the assessment of gastric bacterial Helicobacter pylori infection, gastric emptying, liver and pancreatic function as well as measurements of many other enzyme activities. The knowledge of potential pitfalls and influencing factors are important for correct interpretation of breath test results before drawing clinical conclusions.
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Affiliation(s)
- Barbara Braden
- John Radcliffe Hospital, Headley Way, OX3 9DU Oxford, UK.
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7
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Abstract
AIM: To validate an optimized 13C-urea breath test (13C-UBT) protocol for the diagnosis of H pylori infection that is cost-efficient and maintains excellent diagnostic accuracy.
METHODS: 70 healthy volunteers were tested with two simplified 13C-UBT protocols, with test meal (Protocol 2) and without test meal (Protocol 1). Breath samples were collected at 10, 20 and 30 min after ingestion of 50 mg 13C-urea dissolved in 10 mL of water, taken as a single swallow, followed by 200 mL of water (pH 6.0) and a circular motion around the waistline to homogenize the urea solution. Performance of both protocols was analyzed at various cut-off values. Results were validated against the European protocol.
RESULTS: According to the reference protocol, 65.7% individuals were positive for H pylori infection and 34.3% were negative. There were no significant differences in the ability of both protocols to correctly identify positive and negative H pylori individuals. However, only Protocol 1 with no test meal achieved accuracy, sensitivity, specificity, positive and negative predictive values of 100%. The highest values achieved by Protocol 2 were 98.57%, 97.83%, 100%, 100% and 100%, respectively.
CONCLUSION: A 10 min, 50 mg 13C-UBT with no test meal using a cut-off value of 2-2.5 is a highly accurate test for the diagnosis of H pylori infection at a reduced cost.
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Jolley CD, Wagner DA. Comparison of the 13C-urea blood test to histology and rapid urease testing in the diagnosis of Helicobacter pylori infection in children. J Pediatr Gastroenterol Nutr 2007; 44:68-70. [PMID: 17204956 DOI: 10.1097/01.mpg.0000243426.78721.bc] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE Helicobacter pylori infection is commonly investigated in children with abdominal pain. The definitive means of diagnosing infection, histology, requires endoscopy and sedation, making it invasive and expensive. Our objective was to compare histology against a less invasive and safer method, the 13C-urea blood test. PATIENTS AND METHODS Forty children with abdominal pain undergoing upper endoscopy were randomized into either of 2 dosages of 13C-urea. Several biopsies were taken for histology and rapid urease testing. After endoscopy, each child ingested a randomly assigned dosage of either 75 mg or 125 mg 13C-urea, and blood was withdrawn 30 min later. RESULTS Irrespective of the dosage of 13C-urea, the 13C-urea blood test performed with high accuracy (89%) when compared against either histology or rapid urease testing. The sensitivity and specificity of the blood test was 83% and 91%, respectively. When the smaller dosage of 13C-urea was used, the accuracy of the blood test was 100% compared with histology. There were no adverse events related to using either dosage of 13C-urea. CONCLUSIONS The 13C-urea blood test may be comparable with histology in diagnosing H. pylori infection in children, and the smaller dosage of 13C-urea does not adversely affect blood test performance. The 13C-urea blood test is well tolerated in children.
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Schneider A, Caspary WF, Saich R, Dietrich CF, Sarrazin C, Kuker W, Braden B. 13C-methacetin breath test shortened: 2-point-measurements after 15 minutes reliably indicate the presence of liver cirrhosis. J Clin Gastroenterol 2007; 41:33-7. [PMID: 17198062 DOI: 10.1097/mcg.0b013e31802dd4b9] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND GOALS The 13C-methacetin breath test (MBT) measures the activity of the cytochrome P450 dependent enzyme system and has been developed to assess the functional hepatic mass. We evaluated simple modifications of the 13C-MBT to further increase its practicability and therefore clinical acceptance. STUDY One hundred and four patients with different chronic liver diseases (including 35 patients with histologically proven cirrhosis) and 65 healthy controls underwent the 13C-MBT. Breath test results of 2-point measurements were compared with conventional breath test results (cumulative recovery after 30 min) and liver histology. RESULTS The 2-point-measurement at 0 and 15 minutes (with a cut-off <14.6 per thousand delta over baseline) had 92.6% sensitivity and 94.1% specificity in identifying the presence of cirrhosis compared with liver histology. The 2-point-measurements at 5 and 10 minutes also provided good discrimination between cirrhotic and noncirrhotic patients. CONCLUSIONS The 13C-MBT using 2-point-measurement of breath samples at baseline and after 15 minutes reliably indicates decreased liver function in liver cirrhosis. This simplification of the 13C-MBT will increase practicability and cost efficiency, thus facilitating its clinical acceptability.
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Affiliation(s)
- Arne Schneider
- Medical Department I, Johann Wolfgang Goethe University of Frankfurt/Main, Germany
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10
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Kopácová M, Bures J, Vorísek V, Konstacký M, Rejchrt S, Zivný P, Douda T, Palicka V. Comparison of different protocols for 13C-urea breath test for the diagnosis of Helicobacter pylori infection in healthy volunteers. Scandinavian Journal of Clinical and Laboratory Investigation 2005; 65:491-8. [PMID: 16179282 DOI: 10.1080/00365510500209199] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE The (13)C-urea breath test ((13)C-UBT) is the most accurate non-invasive method for diagnosis of Helicobacter pylori infection. However, several methodological issues have not been resolved yet. The aim of this study was to test different protocols of (13)C-UBT to find the optimal test drink and sampling interval. MATERIAL AND METHODS (13)C-UBT was performed at 3-day intervals in 27 healthy volunteers using citric acid (test A), orange juice (B) and still water (C) as test drinks. Breath samples were collected from time 5 to 60 min. A total number of 2106 breath samples were analysed by isotope ratio mass spectrometry (cut-off value 3.5). RESULTS Differences in delta values were greater than would be expected by chance (A versus B and A versus C at times 20, 25, 30, 35 and 40 min, p<0.05, Dunnett's method). There were no grey zone- or false-negative results among H. pylori-positive persons in test A at any time, but some were found in tests B and C. Optimal intervals for breath sampling are at times 20 or 25 min after (13)C-urea ingestion. CONCLUSIONS Citric acid solution as a test drink and 20- or 25-min breath sampling intervals are optimal for the (13)C-UBT in healthy volunteers.
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Affiliation(s)
- M Kopácová
- Second Department of Internal Medicine, Charles University, Prague, Czech Republic.
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Gisbert JP, González-Lama Y. [Breath tests in the diagnosis of gastrointestinal diseases]. GASTROENTEROLOGIA Y HEPATOLOGIA 2005; 28:407-16. [PMID: 16137476 DOI: 10.1157/13077762] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Determination of carbon or hydrogen markers in breath has allowed closer investigation of the pathogenic mechanisms of several gastrointestinal diseases. Thus, the 13C-urea breath test is a nonaggressive, simple and safe test with excellent accuracy both in the initial diagnosis of Helicobacter pylori infection and in confirmation of its eradication following treatment. Moreover, because of the simplicity, reproducibility and safety of these types of procedure, they have tended to substitute more uncomfortable and expensive techniques that were traditionally used in gastroenterology. Several breath tests have been developed that allow reliable evaluation of liver or exocrine pancreatic function, gastrointestinal motility, as related to gastric emptying or orocecal transit time, and a diagnostic approach to clinical problems that could be due to bacterial overgrowth or malabsorption of various sugars.
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Affiliation(s)
- J P Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de la Princesa, Madrid, España.
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Bühling F, Peitz U, Krüger S, Küster D, Vieth M, Gebert I, Roessner A, Weber E, Malfertheiner P, Wex T. Cathepsins K, L, B, X and W are differentially expressed in normal and chronically inflamed gastric mucosa. Biol Chem 2005; 385:439-45. [PMID: 15196006 DOI: 10.1515/bc.2004.051] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
The expression of cathepsins K, L, B, X and W was studied by quantitative RT-PCR in normal and inflamed gastric mucosa (antrum, corpus, cardia). Cathepsins B, L, K and X were expressed ubiquitously. In contrast, cathepsin W was expressed at very low levels. Infection by Helicobacter pylori caused a significant induction of cathepsin X (p<0.008), whereas the other cathepsins were not or only locally affected by H. pylori infection or reflux disease. Immunohistochemistry revealed specific expression of cathepsin X (macrophages), cathepsin K (parietal cells) and cathepsin W (lymphocytes), whereas cathepsins B and L were predominantly expressed in epithelial cells.
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Affiliation(s)
- Frank Bühling
- Institute of Immunology, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany
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Gisbert JP, Pajares JM. Review article: 13C-urea breath test in the diagnosis of Helicobacter pylori infection -- a critical review. Aliment Pharmacol Ther 2004; 20:1001-17. [PMID: 15569102 DOI: 10.1111/j.1365-2036.2004.02203.x] [Citation(s) in RCA: 253] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The urea breath test is a non-invasive, simple and safe test which provides excellent accuracy both for the initial diagnosis of Helicobacter pylori infection and for the confirmation of its eradication after treatment. Some studies have found no differences between urea breath test performed under non-fasting conditions. The simplicity, good tolerance and economy of the citric acid test meal probably make its systematic use advisable. The urea breath test protocol may be performed with relatively low doses (<100 mg) of urea: 75 mg or even 50 mg seem to be sufficient. With the most widely used protocol (with citric acid and 75 mg of urea), excellent accuracy is obtained when breath samples are collected as early as 10-15 min after urea ingestion. A unique and generally proposed cut-off level is not possible because it has to be adapted to different factors, such as the test meal, the dose and type of urea, or the pre-/post-treatment setting. Fortunately, because positive and negative urea breath test results tend to cluster outside of the range between 2 and 5 per thousand, a change in cut-off value within this range would be expected to have little effect on clinical accuracy of the test.
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Affiliation(s)
- J P Gisbert
- Department of Gastroenterology, University Hospital of La Princesa, Madrid, Spain.
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Annibale B, Lahner E, Chistolini A, Gallucci C, Di Giulio E, Capurso G, Luana O, Monarca B, Fave GD. Endoscopic Evaluation of the Upper Gastrointestinal Tract is Worthwhile in Premenopausal Women with Iron-Deficiency Anaemia Irrespective of Menstrual Flow. Scand J Gastroenterol 2003; 38:239-245. [PMID: 12737437 DOI: 10.1080/00365520310000690a] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND In premenopausal women, iron-deficiency anaemia is common and menstrual flow is often held responsible, but it is not clear whether these women should be submitted to gastrointestinal (GI) evaluation. We aim to prospectively investigate whether premenopausal women with iron-deficiency anaemia benefit from GI evaluation regardless of menstrual flow. METHODS The study population comprised 59 consecutive premenopausal women with iron-deficiency anaemia. Excluded were women with obvious or suspected causes of anaemia and those ≤21 years. Heavy menstrual loss was not considered an exclusion criterion. All subjects had: complete blood count, ferritin, non-invasive testing by faecal occult blood (FOB), 13C-urea breath test (13C-UBT), anti-tissue transglutaminase antibodies (tTG) and gastrin levels. Gastroscopy with antral (n = 3), corporal (n = 3) and duodenal (n = 2) biopsies was performed in women with positive 13C-UBT or tTG titre or hypergastrinaemia. RESULTS Heavy menstrual loss was present in 50.8%. Non-invasive tests were positive in 40/59 (67.8%): 30 had positive 13C-UBT, 12 had hypergastrinaemia, 7 had positive tTG and 3 had positive FOB. Women tested positive were similar to those tested negative as far as concerned age, haemoglobin and ferritin levels and heavy menstrual flow (55% versus 42.1%). All 40 women tested positive underwent gastroscopy with biopsies. Four (10%) had bleeding-associated lesions and 34 (85%) had non-bleeding-associated lesions. As regards upper GI findings, no differences were observed between women with normal and those with heavy menstrual flow. No lower GI tract lesions were detected in the three women with positive FOB. CONCLUSIONS Our data suggest that premenopausal women with iron-deficiency anaemia benefit from endoscopic evaluation of the upper GI tract irrespective of menstrual flow.
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Affiliation(s)
- B Annibale
- a Digestive and Liver Disease Unit , 2nd Medical School, Policlinico Universitario Ospedale 'Sant' Andrea' , and Dept. of Haematology , University 'La Sapienza' , Rome , Italy
| | - E Lahner
- a Digestive and Liver Disease Unit , 2nd Medical School, Policlinico Universitario Ospedale 'Sant' Andrea' , and Dept. of Haematology , University 'La Sapienza' , Rome , Italy
| | - A Chistolini
- a Digestive and Liver Disease Unit , 2nd Medical School, Policlinico Universitario Ospedale 'Sant' Andrea' , and Dept. of Haematology , University 'La Sapienza' , Rome , Italy
| | - C Gallucci
- a Digestive and Liver Disease Unit , 2nd Medical School, Policlinico Universitario Ospedale 'Sant' Andrea' , and Dept. of Haematology , University 'La Sapienza' , Rome , Italy
| | - E Di Giulio
- a Digestive and Liver Disease Unit , 2nd Medical School, Policlinico Universitario Ospedale 'Sant' Andrea' , and Dept. of Haematology , University 'La Sapienza' , Rome , Italy
| | - G Capurso
- a Digestive and Liver Disease Unit , 2nd Medical School, Policlinico Universitario Ospedale 'Sant' Andrea' , and Dept. of Haematology , University 'La Sapienza' , Rome , Italy
| | - O Luana
- a Digestive and Liver Disease Unit , 2nd Medical School, Policlinico Universitario Ospedale 'Sant' Andrea' , and Dept. of Haematology , University 'La Sapienza' , Rome , Italy
| | - B Monarca
- a Digestive and Liver Disease Unit , 2nd Medical School, Policlinico Universitario Ospedale 'Sant' Andrea' , and Dept. of Haematology , University 'La Sapienza' , Rome , Italy
| | - G Delle Fave
- a Digestive and Liver Disease Unit , 2nd Medical School, Policlinico Universitario Ospedale 'Sant' Andrea' , and Dept. of Haematology , University 'La Sapienza' , Rome , Italy
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Abstract
A large number of diagnostic tests are available for the diagnosis of Helicobacter pylori infection. These diagnostic methods include invasive and noninvasive methods. Culture yields the highest specificity and moreover allows the determination of strain resistance against antibiotics. Histology besides detection of H. pylori allows to assess morphological changes of the gastric mucosa. In clinical practice, the rapid urease test is very convenient and highly accurate. The (13)C-urea breath test and the recently developed stool antigen test are reliable noninvasive tests with a high diagnostic accuracy in pre- and posttreatment conditions. Serological tests have a lower diagnostic accuracy and should only be used for screening of H. pylori infection or after careful local validation.
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Affiliation(s)
- A Leodolter
- Department of Gastroenterology, Hepatology and Infectiology, Otto von Guericke University, Magdeburg, Germany
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16
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Chung IK, Hong SJ, Kim EJ, Cho JY, Kim HS, Park SH, Lee MH, Kim SJ, Shim CS. What is the best method to diagnose Helicobacter infection in bleeding peptic ulcers?: a prospective trial. Korean J Intern Med 2001; 16:147-52. [PMID: 11769572 PMCID: PMC4531724 DOI: 10.3904/kjim.2001.16.3.147] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND It has been debated which diagnostic test should be preferred for the diagnosis of Helicobacter pylori (HP) in patients with peptic ulcer diseases. Several limitations are reported in bleeding peptic ulcers because of intragastric blood and possibility of changed numbers of organisms by medication. This study was designed to find out the best method for diagnosis of HP infection, in aspect of deciding the times of detection and the specific tests in bleeding peptic ulcers. METHODS We prospectively examined histology, rapid urease test (CLO test), urea breath test (13C-UBT) and serology in HP diagnostics in 32 patients with bleeding peptic ulcers to detect HP infection. Each test was performed two times (four methods at first 24 hours and former three methods at 7th day after initial therapeutic endoscopy). We evaluated the sensitivity of each test, compared the two-times results and evaluated the effect of these tests to an outcome of endoscopic hemostasis. RESULTS Diagnostic sensitivities of histology, CLO test, 13C-UBT and serology are 75%, 67.8%, 100% and 100% at first endoscopy, and 71.4%, 78.5%, 89.3% at 7th day endoscopy, respectively. Histologic study and CLO test had diagnostic limitation at emergent first endoscopy contrary to UBT (p < 0.01). Histologic study, CLO test and UBT have limitations at 7th day endoscopy. Only 3 patients (9.4%) rebled with subsequent complete endoscopic hemostasis and all diagnostic tests at initial endoscopy did not influence the outcome of hemostasis. CONCLUSION First day histologic and CLO tests are inadequate methods in detecting HP infection in patients with bleeding peptic ulcers. 7-day histologic, CLO test and UBT have a low sensitivity. First-day UBT can be a standard test to diagnose HP infection in patients with bleeding peptic ulcers.
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Affiliation(s)
- I K Chung
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University Chonan Hospital, Institute of Digestive Disease Research, Korea
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17
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Vaira D, Holton J, Menegatti M, Ricci C, Gatta L, Geminiani A, Miglioli M. Review article:invasive and non-invasive tests for Helicobacter pylori infection. Aliment Pharmacol Ther 2000; 14 Suppl 3:13-22. [PMID: 11050483 DOI: 10.1046/j.1365-2036.2000.00096.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
There are two general ways in which a diagnosis of infection by Helicobacter pylori can be made: by using either an invasive or non-invasive procedure. The invasive procedures involve an endoscopy and biopsy. A biopsy is essential because often the mucosa may appear macroscopically normal but nevertheless be inflamed. A biopsy is obtained by histological examination, culture, polymerase chain reaction or detection of the presence of urease activity in biopsy material. The non-invasive tests that can be used to diagnose the infection are serology, detection of labelled metabolic products of urea hydrolysis in the breath (13CO2, 14CO2), the urine or the blood, and detection of H, pylori antigen in a stool specimen. At present no single test can be relied upon to detect definitely colonization by H. pylori, and a combination of two is recommended if this is feasible. The choice of the test to be used is not straightforward and may vary according to the clinical condition and local expertise.
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Affiliation(s)
- D Vaira
- Ist Medical Clinic, University of Bologna, Italy.
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18
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Di Leo A, Messa C, Russo F, Linsalata M, Amati L, Caradonna L, Pece S, Pellegrino NM, Caccavo D, Antonaci S, Jirillo E. Helicobacter pylori infection and host cell responses. Immunopharmacol Immunotoxicol 1999; 21:803-46. [PMID: 10584213 DOI: 10.3109/08923979909007143] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
It is well known that Helicobacter pylori is able to colonize the gastric mucosa, causing a chronic and persistent infection with complications, such as peptic ulcer and gastric cancer. This review places emphasis on some epidemiological aspects of Helicobacter pylori infection and its mode of transmission. At the same time, invasive and non-invasive methods of diagnosis of Helicobacter pylori infection are illustrated. More space is devoted to the host response following invasion of the stomach. In this respect, the role played by different growth factors and polyamines in the course of Helicobacter pylori disease is discussed also in relation to the result of eradicating treatment. On the other hand, an accurate description of the host immune responses against Helicobacter pylori organism and/or their components (e.g. lipopolysaccharides) is reported. Finally, since Helicobacter pylori has been classified as a class I carcinogen, current researches are focussed on the Helicobacter pylori-induced carcinogenesis.
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Affiliation(s)
- A Di Leo
- Laboratory of Biochemistry, IRCCS Saverio de Bellis, Castellana Grotte, Bari, Italy
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Leodolter A, Domínguez-Muñoz JE, von Arnim U, Kahl S, Peitz U, Malfertheiner P. Validity of a modified 13C-urea breath test for pre- and posttreatment diagnosis of Helicobacter pylori infection in the routine clinical setting. Am J Gastroenterol 1999; 94:2100-4. [PMID: 10445534 DOI: 10.1111/j.1572-0241.1999.01284.x] [Citation(s) in RCA: 59] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Citric acid meets the criteria of an optimal test drink for the 13C-urea breath test (13C-UBT) because it permits rapid, high level recovery of the 13C administered. In a previous study we reported that administration of 13C-urea dissolved in a citric acid solution provides results similar to those obtained with standard administration of the substrate 10 min after the test drink. The aim of this study was to evaluate the accuracy of this modified 13C-UBT for both primary and posttreatment diagnosis of Helicobacter pylori (H. pylori) infection in a large patient population in clinical practice. METHODS The 13C-UBT was performed in 553 patients with dyspeptic symptoms by giving them 75 mg of 13C-urea either 10 min after administration of 200 ml of a test drink comprising 0.1 mol/L citric acid solution (protocol 1, n = 320) or dissolved in the same amount of this test drink (protocol 2, n = 233). All patients underwent an upper gastrointestinal endoscopy and the H. pylori-status was assessed by histology, rapid urease test, and culture. Sixty patients with proven H. pylori infection were reinvestigated by both endoscopy and 13C-UBT (protocol 2) 4 wk after completing eradication therapy. RESULTS The accuracy of the two test protocols in the pretreatment diagnosis of H. pylori infection (95.6% and 96.6%), as well as of the modified 13C-UBT in the posttreatment evaluation of the infection (98.3%) was similar. More meaningful are the high PPV (>96%) and NPV (>93%) of the 13C-UBT under pre- and posttreatment conditions. CONCLUSIONS The administration of 13C-urea dissolved in a citric acid solution simplifies the 13C-UBT, while preserving the high accuracy in the diagnosis of H. pylori infection. This modified 13C-UBT has equal accuracy in the pre- and the posttreatment situations.
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Affiliation(s)
- A Leodolter
- Department of Gastroenterology, University of Magdeburg, Germany
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Leodolter A, Domínguez-Muñoz JE, Von Arnim U, Malfertheiner P. Citric acid or orange juice for the 13C-urea breath test: the impact of pH and gastric emptying. Aliment Pharmacol Ther 1999; 13:1057-62. [PMID: 10468681 DOI: 10.1046/j.1365-2036.1999.00557.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND There is an ongoing debate about the optimal test drink to be used in the 13C-urea breath test (13C-UBT). We recently reported that a citric acid solution is the optimal test drink in the 13C-UBT, because it provides a high 13CO2 recovery and the excellent accuracy of the test appears optimal compared to other test meals. Orange juice, because of a better taste, is also propagated as a test drink in the 13C-UBT. AIM To compare the diagnostic accuracy of the 13C-UBT with either orange juice or citric acid solution as a test drink. Furthermore, the effect of these test drinks on the gastric emptying rate was determined. METHODS H. pylori status was assessed by histology, rapid urease test and culture in 50 consecutive dyspeptic patients. A 13C-UBT was performed on two consecutive days by giving 75 mg of 13C-urea randomly dissolved in 200 mL 0.1 M citric acid solution or 200 mL orange juice. The 13CO2/12CO2 ratio was measured in breath samples taken before and 15, 30, 45 and 60 min after administration of the test drink. The gastric emptying rate of orange juice and citric acid solution was compared to that of water in 10 healthy subjects on three consecutive days by means of a 13C-sodium acetate breath test; 50 mg of 13C-sodium acetate was dissolved in 200 mL of each solution and breath samples were collected before and every 10 min for 90 min after administration of the test drink. RESULTS Twenty-six out of 50 patients (52%) were infected with H. pylori. Significantly higher values over baseline (35.7+/-5.2 per thousand vs. 23.2+/-3.4 per thousand, P<0.001) and higher area under the curve (1507+/-198 vs. 927+/-128, P<0.001) were observed in H. pylori-positive patients when citric acid solution was administered compared with orange juice. Sensitivity of the 13C-UBT was 100% when citric acid was used as a test drink and 88% with orange juice. Specificity was 100% with both test drinks. Gastric emptying of citric acid solution (t1/2 = 60.9+/-3.5 min) was significantly slower than that of orange juice (t1/2 = 49.7+/-3.1 min, P<0.001). CONCLUSION 13C-UBT loses diagnostic accuracy when orange juice instead of citric acid is used as a test drink. The faster gastric emptying of orange juice might be responsible for the lower diagnostic accuracy of the 13C-UBT.
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Affiliation(s)
- A Leodolter
- Department of Gastroenterology, Hepatology and Infectious Diseases, University of Magdeburg, Germany
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