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1.
OBJECTIVE: To validate a simplified 13C-urea breath test (13C-UBT) method for the diagnosis of H. pylori infection. MATERIAL AND METHODS: Patients referred for gastrointestinal endoscopy and biopsy were included, and a 13C-UBT was performed after a 6-hour fast. Breath samples were collected in 10 ml glass tubes before and 30 min after the simultaneous administration of 50 mg of 13C-urea and 2 g of citric acid in 200 ml of water. All breath samples were analyzed using isotope ratio mass spectrometry. The diagnosis of H. pylori infection was established with a positive culture and/or positive histology and serology. RESULTS: Eighty-eight patients were included, 49 female and 39 male with a mean age of 45 +/- 15 yrs. Fifty-one patients (57.95%) were positive and 30 (34.1%) negative for H. pylori. Seven cases (7.95%) were considered undetermined. The sensitivity, specificity, positive predictive value, and negative predictive value for 13C-UBT were 90.2, 93.3, 95.83, and 84.8%, respectively. Accuracy was 91.4%. CONCLUSIONS: The simultaneous administration of 50 mg of 13C-urea and 2 g of citric acid represents an alternative for the non-invasive diagnosis of H. pylori infection.  相似文献   

2.
BACKGROUND: The 13C-urea breath test (13C-UBT) is a simple, non-invasive and reliable test for the diagnosis of Helicobacter pylori infection. The duration of the test, the timing of breath sampling, and the accuracy of the method vary according to the test meal used. AIM: To identify the optimal test meal or drink for rapid and accurate performance of the 13C-UBT for the detection of H pylori infection. PATIENTS: Eighty patients with dyspeptic symptoms were included. Of these, 48 patients had a positive H pylori status and 32 a negative one according to the results of the rapid urease test, histological examination, and culture. METHODS: A 13C-UBT was performed after an overnight fast, on three consecutive days. On each study day a different test meal or drink was given (0.1 N citric acid solution, a standard semiliquid meal, or a semiliquid fatty meal) 10 minutes before giving 75 mg 13C-urea. Breath samples were collected at 0, 15, 30, 45, and 60 minutes, and analysed by isotype ratio mass spectrometry. Results were expressed as delta (delta) and considered as positive for H pylori if the highest delta (peak) was greater than 4.0. RESULTS: The delta peak obtained with the citric acid drink in H pylori positive subjects (24.1 (SEM 1.5)) was significantly higher than that obtained with any of the semiliquid meals (13.3 (SEM 1.1) and 17.1 (SEM 1.0) respectively, p < 0.001). Furthermore, this delta peak was obtained earlier with the citric acid drink (30 (SEM 2) minutes) than with the other two meals tests (53 (SEM 2) min and 45 (SEM 2) min, p < 0.001). The sensitivity of the 13C-UBT for the diagnosis of H pylori infection was 96-100% with all three test meals. This high sensitivity was, however, obtained from 15 minutes by giving citric acid as the test drink, from 45 minutes by giving a semiliquid fatty meal, and at 60 minutes by giving the semiliquid standard meal. The specificity was 100% for all test meals. Citric acid is inexpensive and palatable to patients. CONCLUSIONS: The 13C-UBT procedure with citric acid as the test drink is superior to the previously proposed semiliquid test meals in terms of 13CO2 recovery, time requirement, and cost. In routine clinical sampling, collection at times 0 and 30 minutes seems to be optimal and gives a high diagnostic accuracy.  相似文献   

3.
An optimized 13C-urea breath test for the diagnosis of H pylori infection   总被引:3,自引:0,他引:3  
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 rain 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.  相似文献   

4.
OBJECTIVE: The 13C-urea breath test (13C-UBT) is a safe, noninvasive, and accurate test for the detection of Helicobacter pylori (H. pylori) infection in adults. The aim of this study was to evaluate sensitivity and specificity of 13C-UBT in children using different types of test meal, doses of 13C-urea and breath sampling intervals. As yet, a validated, standardized 13C-UBT protocol for children has not been formulated. METHODS: 13C-UBT was performed in 115 children and repeated within 3 days, modifying the test meal or the dose of 13C-urea. H. pylori status was assessed by histology and rapid urease test. 13C-UBT was performed using 100 mg or 50 mg of 13C-urea and a fatty test meal (100 FA; 50 FA), 50 mg of 13C-urea, and a carbohydrate test meal (50 CA). Breath samples were collected every 10 min for 60 min. RESULTS: The 13C-UBT in children was highly sensitive and specific with all three protocols used. The best combination of sensitivity (97.92%) and specificity (97.96%) was obtained with Protocol 50 FA at 30 min with a cut-off of 3.5 per mil. CONCLUSIONS: The 13C-UBT is an accurate test for the detection of H. pylori infection also in children. Administration of 50 mg of 13C-urea, a fatty test meal, and breath sampling at 30 min appears to be the most convenient protocol.  相似文献   

5.
This study aimed to evaluate the effectiveness of the 13C-urea breath test (UBT) for assessment of Helicobacter pylori eradication after treatment. One hundred twenty six patients were enrolled with 85 receiving proton pomp inhibitor based triple therapy. They were underwent upper gastrointestinal endoscopy with biopsies for diagnosis and assessment of H. pylori infection using culture, histology, rapid urease test (RUT) and 13C-UBT. Assessment of eradication needs to be performed 4 weeks or more after completion of treatment. Breath samples were taken 15 minutes after the ingestion of 100 mg 13C-urea. Breath samples were analyzed on a mass spectrometer system. The gold standard for H. pylori infection was a positive culture or positive histology + positive RUT; negative for infection was defined as negative results of all three biopsy tests. Based on ROC curves, the most appropriate cut-off value for diagnosis of H. pylori infection was identified as 2.5/1000, which provided 96.2% sensitivity, 100% specificity, and 96.8% accuracy as judged by the gold standard. However, when confirming the eradication of H. pylori, it was 3.5/1000, which provides for 100%, 95.8%, and 96.5%, respectively. Ten patients (11.8%) had delta13C values that were 2.5-5.0/1000 4-12 weeks after therapy. Eight patients were considered cured of H. pylori infection, and 2 were considered to still have H. pylori infection following 13C-UBT, serology, and H. pylori specific antigen test. The false-positive rate of 13C-UBT was 9.4% (8/85). When the grey zone of 13C-UBT was set at a level of 2.5 to 5.0/1000 (2.5 > : negative, 5.0 < or = : positive) after eradication therapy, the sensitivity and specificity of 13C-UBT was 100% and 98.4% compared to the gold standard. It was concluded that to avoid false-positive results of 13C-UBT, the grey zone of 13C-UBT needs to be set at a level of 2.5 to 5.0/1000; thus improving the accuracy of test for the assessment of eradication of H. pylori infection.  相似文献   

6.
目的探讨剂量小于常规75~100mg、红外能谱测量法^13C-尿素呼气试验(^13C-UBT)诊断幽门螺杆菌(H.pylori)感染的可行性。方法133例因消化不良进行胃镜检查的门诊患者,胃黏膜活检标本Giemsa染色检查H.pylori,红外能谱测量法进行20mg酸化胶囊^13C-UBT,分别应用ROC法和特异性优先法评价诊断效能。结果59例H.pylori阳性病人和74例阴性病人DOB值分别为5.27±4.49和-0.50±0.98,差异显著(P〈0.05)。ROC法的最适判别值为DOB=0.4时,其诊断敏感性、特异性和准确性分别为91.5%(54/59)、89.2%(66/74)和90.2%(120/133);以特异性优先法的最适判别值为DOB=2.0时,其诊断敏感性、特异性和准确性分别86.4%(51/59)、100%(74/74)和94.0%(125/133)。结论红外能谱测量法小剂量^13C-尿素呼气试验是可行的,但20mg酸化胶囊^13C-尿素呼气试验方案尚不能满足临床诊断需要。  相似文献   

7.
BACKGROUND AND AIM: Infrared spectrometry has correlated excellently with mass spectrometry in detecting the ratio of 13CO(2) to 12CO(2) in breath samples. The present study aimed to evaluate the accuracy of the 13C-urea breath test (13C-UBT) using a new model of infrared analyzer. METHODS: A total of 600 patients who were undergoing upper endoscopy without receiving eradication therapy were entered into the study. Culture, histology, and rapid urease test on biopsies from the antrum and corpus of the stomach were used for the determination of Helicobacter pylori infection. Breath samples were collected before and 20 min after drinking 100 mg 13C-urea in 100 mL water. The optimal cutoff value was determined by the receiver operating characteristic curve. RESULTS: Of the 586 patients who were eligible for analysis, 369 were positive for H. pylori infection, 185 were negative for H. pylori infection, and 32 were indeterminate. When the appropriate cutoff value was set at 3.5 per thousand, a sensitivity of 97.8%, a specificity of 96.8% and an accuracy of 97.5% were obtained using the 13C-UBT. The accuracy of the 13C-UBT decreased when CO(2) concentration in the breath sample was <2%, as compared with > or = 2% (93.6%vs 97.7%), mainly because of a decrease in specificity (81.8%vs 97.7%). There were 2.7% of patients with Delta13CO(2) values that fell between 3.0-4.5 per thousand, in whom the risk of error was 47%. CONCLUSIONS: The 13C-UBT performed with infrared spectrometry is a highly sensitive, specific, and non-invasive method for the detection of H. pylori infection. The immediate availability of the test result and technical simplicity make it particularly effective in routine clinical practice.  相似文献   

8.
9.
目的:验证红外能谱仪检测13C-尿素呼气试验(UBT)诊断幽门螺杆菌(H.pylori)感染的可靠性,并与气体质谱仪检测结果作一比较。方法:对76例患者以红外能谱仪进行13C-UBT检测H. pylori感染,H. pylori感染状态由快速尿素酶试验、组织学检查以及细菌培养确定。其中17例患者的呼气样本分别用红外能谱仪与气体质谱仪进行检测。结果:76例患者中H. pylori阳性者43例(56.6%),红外能谱仪进行13C-UBT的测定结果为41例(53.9%),其敏感性和特异性分别达到93.0%和97.0%。气体质谱仪与红外能谱仪的检测数值相差无几。结论:以红外能谱仪进行13C-UBT检测可靠、准确地诊断H.pylori感染,并具有简单、实用的特点。红外能谱仪与气体质谱仪一样可被广泛应用于H.pylori检测。  相似文献   

10.
BACKGROUND: A Helicobacter pylori stool antigen (HpSA) test has been proposed as a valid alternative to the 13C-urea breath test (13C-UBT) for the non-invasive detection of H. pylori infection in primary diagnosis. Published reports show conflicting results with regard to the test's diagnostic accuracy after eradication therapy. The aim of the present study was to assess the diagnostic value of the HpSA test and to determine the optimal discriminating cut-off value in patients following H. pylori eradication therapy. METHOD: Stool samples were collected and the 13C-UBT was performed in 113 patients 4-6 weeks after eradication therapy. A validated test protocol for the 13C-UBT was used. Stool specimens were analysed with the Premier Platinum HpSA enzyme immunoassay (EIA). A receiver operator characteristics (ROC) analysis was performed to define the optimal cut-off value on the basis of the results of the 13C-UBT. RESULTS: The results of the 13C-UBT showed that H. pylori eradication was successful in 83/113 (73%) patients. According to the manufacturer, the cut-off value for the HpSA test is 0.14 optical density, but this does not appear to be valid after eradication therapy (sensitivity 76.7%, specificity 98.8%). On the basis of ROC analysis, the optimal cut-off value after therapy was determined to be 0.11 optical density, giving a sensitivity of 93.3% and a specificity of 93.9%. CONCLUSION: The HpSA test is a valid test for the assessment of H. pylori status after eradication therapy, provided an adjusted cut-off value is applied.  相似文献   

11.
BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection has a causative relationship with various gastrointestinal disorders. 13C-urea breath test and H. pylori stool antigen test are two valuable noninvasive tests for detecting H. pylori infection. Since the bacterial load of H. pylori in the stomach and the resulting severity of gastritis are important in validating the status of H. pylori infection, we would like to investigate the relative diagnostic accuracy of 13C-urea breath test and H. pylori stool antigen test with respect to the severity of gastritis. METHODOLOGY: The H. pylori statuses of 62 consecutive patients were evaluated by five tests, i.e., culture, histology, biopsy urease test, 13C-urea breath test, and H. pylori stool antigen test. Gastritis was graded by the updated Sydney system. H. pylori status was defined as positive when the culture was positive or the concordance of positivity of two of the other four tests. RESULTS: Thirty-five patients (56%) were H. pylori positive. The accuracy of H. pylori stool antigen test and 13C-urea breath test were 92.6% and 100%, respectively. There was a positive correlation between the level of delta 13CO2 of the 13C-urea breath test and the optical density value of enzyme immunoassay of the H. pylori stool antigen test (Rho = 0.758, P < 0.001). Both the level of delta 13CO2 of 13C-UBT and the optical density value of enzyme immunoassay of the H. pylori stool antigen test correlated well with the separate score of the density of H. pylori (P < 0.001, each) and the inflammatory activity (each P < 0.001). CONCLUSIONS: Both the 13C-urea breath test and H. pylori stool antigen test are effective non-invasive methods to detect the status of H. pylori infection with respect to correlation with the density of H. pylori and inflammatory activity of gastritis.  相似文献   

12.
OBJECTIVE: We tested whether a 13C-urea breath test can predict antimicrobial resistance of Helicobacter pylori (H. pylori). METHODS: Seventy patients who had failed triple eradication therapy and 108 untreated H. pylori-infected patients were given a 13C-urea breath test, endoscopy for culture of H. pylori, and assessment of clarithromycin resistance. The patients who had failed triple therapy then received 1 week of quadruple therapy to eradicate residual H. pylori. RESULTS: The posttreatment value of the 13C-urea breath test expressed as excessive delta13CO2 per ml (ECR) was higher in patients with residual H. pylori with clarithromycin resistance than in those without (23.8 vs 10.6; P<.0001). With a cutoff of ECR >or< or =15, the 13C-urea breath test was 88.6% sensitive and 88.9% specific in predicting clarithromycin resistance of residual H. pylori. The H. pylori eradication rate of the rescue regimen was higher for patients with a posttreatment ECR of the 13C-urea breath test < or =15 than for those with a value >15 (93.8% vs 73.3%; P<.05). In contrast, in treatment-naive H. pylori-infected patients, the pretreatment value of the 13C-urea breath test did not differ between patients infected with clarithromycin-resistant or-sensitive isolates (P>.05). CONCLUSION: The posttreatment value of the 13C-urea breath test is predictive of clarithromycin resistance in residual H. pylori after failed triple therapy and predicts efficacy of the rescue regimen. The value of the noninvasive test is promising for primary care physicians who need to select a rescue regimen without invasive H. pylori culture.  相似文献   

13.
14.
OBJECTIVES: In adults, the 13C-urea breath test (UBT) has been widely used as a noninvasive test of Helicobacter pylori infection because of its high sensitivity and specificity. However, this test is less well established in pediatric practice. The optimum cutoff value and test protocol of the 13C-UBT remains to be established in the pediatric population. The primary purpose of this study was to evaluate diagnostic accuracy of the 13C-UBT for children and to determine its optimum cutoff value. METHODS: A total of 220 Japanese children aged 2-16 yr (mean = 11.9) who underwent upper GI endoscopy and gastric biopsies were finally studied. Endoscopic diagnoses included gastritis (n = 131), gastric ulcer (n = 15), duodenal ulcer (n = 72), and combined ulcer (n = 2). H. pylori infection status was confirmed by biopsy tests including histology, urease test, and culture. With the 13C-UBT, breath samples were obtained at baseline and at 20 min after ingestion of 13C-urea without a test meal and were analyzed by isotope ratio mass spectrometry. Based on biopsy tests, a cutoff value was determined using a receiver operating characteristic curve. In 26 children (seven children infected and 19 noninfected), paired breath samples were also measured by nondispersive infrared spectometry (NDIRS). RESULTS: Biopsy tests demonstrated that 89 children (40%) were infected with H. pylori and 131 children were not infected. There were no statistical differences in mean delta 13C values at 20 min between male and female H. pylori-infected and noninfected patients. A receiver operating characteristic analysis defined the best cutoff value as 3.5 per thousand. The overall sensitivity and specificity at a cutoff value of 3.5 per thousand were 97.8% (95% CI = 92.1-99.7%) and 98.5% (95% CI = 96.4-100%), respectively: high sensitivity and specificity were demonstrated in all three age groups (< or =5, 6-10, and > or = 11 yr). There was a close correlation between the values with isotope ratio mass spectrometry and NDIRS methods (r = 0.998, p < 0.001). CONCLUSIONS: The 13C-UBT with a cutoff value of 3.5 per thousand is an accurate diagnostic method for active H. pylori infection. The test with the NDIRS method is inexpensive and might be widely applied in clinical practice.  相似文献   

15.
幽门螺杆菌感染诊断方法的比较   总被引:5,自引:1,他引:5  
338例病人同时进行了快速尿素酶试验(简称RUT)。Warthin-Starry染色(简称W-S染色)、培养法、~(13)C-尿素呼气试验(~(13)C-UBT)、血清IgG、IgM等6种诊断方法中任意3种检查,以同时2种(或以上)检查方法一致的结果作为诊断幽门螺杆菌(Hp)是否存在的标准。对上述6种方法的敏感性、特异性、符合率、阳性预测值、阴性预测值分别给予评价,结果显示:RUT、W-S染色、~(13)C-UBT三法诊断Hp的敏感性、特异性等较高,均接近或高于90%。  相似文献   

16.
BACKGROUND: Endoscopic 13C-urea breath test may avoid contamination of oral urease and rapidly discriminate Helicobacter pylori-positive and Helicobacter pylori-negative patients. AIMS: To compare the accuracy of endoscopic 13C-urea breath test with conventional invasive methods in diagnosis of Helicobacter pylori infection. PATIENTS: One hundred patients who attended for routine upper gastrointestinal endoscopy were included. METHODS: 13C-urea was applied to the stomach through the working channel of endoscope at the end of endoscopic examination. Breath samples were collected before endoscopy and 2, 4, 6, 8, 10 min after consumption of 100 or 50 mg 13C-urea. Helicobacter pylori infection was defined as those with positive culture or positive results of both histology and CLO test. RESULTS: The accuracy of 100 mg endoscopic 13C-urea breath test was significantly higher than that of culture and CLO test (100% vs. 88% and 92%, p = 0.02 and 0.03, respectively). The accuracy of 50 mg endoscopic 13C-urea breath test was higher than that of histology and CLO test (98% vs. 90% and 96%, respectively), although the differences were not statistically significant. CONCLUSIONS: Endoscopic 13C-urea breath test has a higher accuracy compared with biopsy-based modalities. It may be a good choice to diagnose Helicobacter pylori infection if endoscopy is indicated for a dyspeptic patient.  相似文献   

17.
AIMS: We investigated the diagnostic properties of the (13)C-urea breath test ((13)C-UBT) prospectively. These are well validated in nonresected patients before and after treatment of Helicobacter pylori infection but not in patients with partial gastric resection due to peptic ulcer disease. METHODS: Hospitalized patients with previous gastric resection and indications for upper gastrointestinal endoscopy were recruited for the study. Biopsy specimens were obtained from the fundus mucosa and the gastric remnant adjacent to the gastroenteric anastomosis for histological examination and rapid urease test (HUT test). Histological slides were evaluated after hematoxylin and eosin and Warthin-Starry dye staining. 200 ml orange juice was given orally after two baseline breath samples had been taken, and 30 min after ingestion of 75 mg (13)C urea two more breath samples were obtained and analyzed by ratio mass spectrometry. The Warthin-Starry dye-stained sample was taken as reference. RESULTS: 68 patients (47 male, 21 female, mean age 62 years; 52 Billroth II resection, 17 Billroth I resection) were included in the study. The overall prevalence of histologically proven H. pylori infection was 36.7%. The sensitivity of the (13)C-UBT was 52%, the specificity 93%. The positive predictive value was 81.25%, the negative predictive value 76.9% and the accuracy was 77.9%. The sensitivity of the HUT test reached 60%, and the specificity 97%. CONCLUSION: The diagnostic accuracy of (13)C-UBT compared with the Warthin-Starry dye staining is low. The breath test, performed in the above-described manner, cannot be recommended as a noninvasive diagnostic tool for diagnosis of H. pylori infection in patients after partial gastrectomy as a result of peptic ulcer disease.  相似文献   

18.
The conventional 13C-urea breath test (13C-UBT) for detecting Helicobacter pylori infection was performed during fasting state and with a test meal to delay gastric emptying during the test. For the convenience of propagating this test, we assessed the availability of non-fast and without test meal in 13C-UBT for the diagnosis of H. pylori infection. One hundred and five consecutive patients who received endoscopic examination were studied. All of them received endoscopic biopsy for urease test, culture and histopathology to determine whether there was a presence of H. pylori infection. Each patient received four separate 13C-UBT under the following four testing conditions. Test I) fasting state with test meal (100 ml fresh milk), Test II) non-fast (taking usual food) but with test meal, Test III) fasting state without test meal, and Test IV) non-fast and without test meal. The excess delta 13CO2 values were calculated via the breathed samples that were collected at 15 minutes after ingestion of 13C-urea. There were 61 H. pylori positive and 44 negative patients in this study, with an excess delta 13CO2 values 3.0, 4.0, 3.5 and 4.0 as a cut-off value in the four tests respectively, according to the ROC curve. The results of test I, a conventional procedure, had a good correlation with the gold standard. The sensitivity and specificity were 100% and 95% respectively. The alternative procedures in other tests also have high sensitivity and specificity at 15-minute detecting time. The sensitivity of the tests II, III and IV at 15-minute detecting times were 98%, 98% and 100%, and the specificities of those were 95%, 98% and 95% respectively. We therefore suggest that fasting and test meal possibly be omitted when the cut-off value is 4.0 per mil in the simplified 13C-UBT (non-fast and without test meal, and detection at 15 minutes after ingestion of 13C-urea) which is a simple and available procedure for clinical diagnosis of H. pylori infection.  相似文献   

19.
目的通过电子胃镜检查及^13C呼气试验(^13C-UBT)检测,以了解幽门螺杆菌感染情况及相应的胃镜表现,为幽门螺杆菌感染引起胃肠道病变提供确切的临床诊断依据。方法对73例有腹痛症状的患儿进行^13C呼气试验(^13C-UBT)检测幽门螺杆菌感染情况,并行电子胃镜检查,观察胃镜下胃肠黏膜病变情况,对幽门螺杆菌感染与胃肠黏膜病变的关系进行分析。结果幽门螺杆菌感染的阳性率为43.84%;男性明显多于女性,学龄期组阳性率高于学龄前组。幽门螺杆菌感染引起胃肠黏膜病变以十二指肠球部溃疡占比最高,其次为结节性胃炎。结论^13C-UBT及胃镜检查应用为幽门螺杆菌感染引起胃肠道黏膜病变诊断提供确切的依据。  相似文献   

20.
Current standards in the diagnosis of Helicobacter pylori infection   总被引:1,自引:0,他引:1  
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.  相似文献   

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