Diagnosis of Helicobacter pylori infection in the elderly using an immunochromatographic assay-based stool antigen test
Graphical Abstract
The prevalence of Helicobacter pylori infection is elevated along with increasing age. Compared with the 13C-urea breath test, the immunochromatographic assay-based stool antigen test achieves excellent accuracy with high specificity but suboptimal sensitivity in the male elderly population before and after the eradication of H. pylori. Caution is needed when applying this test to patients with constipation, which can reduce the sensitivity of the stool antigen test.
Abstract
The diagnostic value of Helicobacter pylori stool antigen (HpSA) tests in elderly subjects remains unclear. The objective of this study was to assess the diagnostic accuracy of the immunochromatographic assay-based HpSA test in a male elderly cohort and identify factors affecting the accuracy. Data for asymptomatic elderly male citizens (≥65 years old) who received health checkups at the Chinese PLA General Hospital between July 2007 and November 2018 were collected. The diagnostic accuracy of the HpSA test was determined using the 13C-urea breath test as a reference standard. Associations between baseline comorbidities and the accuracy of the HpSA test were analyzed. In total, 316 participants were enrolled, including 193 in the pre-treatment group (77.2 ± 7.8 years old) and 123 in the post-treatment group (78.7 ± 8.3 years old). The accuracy (91.5%, 91.2%, and 91.9%) and specificity (97.6%, 98.7%, and 96.0%) were high in all participants, pre- and post-treatment groups, respectively. However, sensitivities were only 68.7%, 65.1%, and 75.0%, respectively. In the pre-treatment group, constipation was associated with decreased sensitivity (p = 0.039), while colorectal polyps were associated with increased sensitivity (p = 0.010). Multivariate analysis indicated that constipation and colorectal polyps are independent factors for the sensitivity of HpSA in the pre-treatment group. The immunochromatographic assay-based HpSA test achieved high accuracy with high specificity but suboptimal sensitivity in the elderly male cohort. Constipation and colorectal polyps were negatively and positively associated with HpSA sensitivity, respectively, in the pre-treatment group.
1 INTRODUCTION
Helicobacter pylori infection is considered an infectious disease, regardless of symptoms and the stage of the disease (Sugano, Tack, & Kuipers, 2015). Along with increasing age, the prevalence of H. pylori infection is elevated in developing countries (Bardhan, 1997). The reliable diagnosis of H. pylori infection is of utmost importance for identifying the source of infection, preventing complications related to chronic H. pylori infection, and monitoring the treatment response after H. pylori eradication.
Several invasive and noninvasive diagnostic methods for H. pylori infection are available (Makristathis, Hirschl, & Megraud, 2019). Invasive tests, such as histopathology, H. pylori culture, rapid urease tests, and modern molecular tests (e.g., real-time quantitative PCR techniques), require gastroscopy with gastric mucosa biopsies, may need specialized laboratory facilities, and are time-consuming. Thus, researches have focused on noninvasive methods, such as the urea breath test (UBT), H. pylori stool antigen (HpSA) test, and serological assays. UBT is capable of identifying active H. pylori infections and is the most widely studied and preferentially recommended a noninvasive approach for the “test-and-treat strategy” (Malfertheiner et al., 2017). The 13C-UBT is the best approach for the detection of H. pylori infection, with outstanding sensitivity, specificity, and performance (Gisbert & Calvet, 2013; Gisbert & Pajares, 2004a). However, the high price and the need for skilled technical staff and complicated instruments limit the application of UBT in clinical practice. As H. pylori antibodies may remain positive for several months or longer after the eradication of bacteria, it is difficult to distinguish between current and past infections using serologic tests (Bergey, Marchildon, Peacock, & Megraud, 2003).
The HpSA test detects bacterial antigens and thus can diagnose active infections. It is easy to perform, especially for pediatric and geriatric patients, those with asthma, after gastrectomy, or in the case of achlorhydria, those in which breath test results are unreliable (Yang & Seo, 2008). It is a noninvasive alternative to UBT (Korkmaz, Kesli, & Karabagli, 2013). Previous HpSA tests with poly-/monoclonal antibodies have shown a sensitivity of 0.83 at a fixed specificity of 0.9 and a ratio of diagnostic odds ratios of 0.88 for the 13C-UBT versus the stool antigen test (Best et al., 2018). The HpSA test can be organized into three groups: immunochromatographic assays (ICA), enzymatic immunoassays (EIA), and immunodot blot assays. H. pylori stool antigens can be easily and rapidly detected using the ICA-based HpSA test, with reported sensitivity and specificity values exceeding 90% both before and after H. pylori treatment (Gatta et al., 2004). There is no significant difference in diagnostic accuracy between ICA-based tests and EIA-based tests in children (Yang & Seo, 2008).
The diagnostic value of the HpSA test in elderly patients remains unclear. Only a few reports involving small sample sizes have evaluated HpSA tests in these patients (Inelmen et al., 2004; Kamel et al., 2011; Salles-Montaudon, Dertheil, & Broutet, 2001, 2002). The objective of this study was to evaluate the sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and diagnostic accuracy of the ICA-based HpSA test in an elderly male cohort using the 13C-UBT as a reference standard. As elderly individuals often have concurrent chronic diseases, we adjusted their baseline comorbidities to investigate the factors related to the accuracy of ICA-based HpSA tests in the study population.
2 MATERIALS AND METHODS
2.1 Participants
Clinical data for elderly male citizens (age ≥65 years) who underwent health checks at the Chinese PLA General Hospital between July 2007 and November 2018 were collected. All participants received the 13C-UBT examination and ICA-based HpSA test. Stool samples were obtained for the HpSA test, which was performed on the same day or no longer than 1 week before or after the 13C-UBT. Subjects who took antibiotics, proton-pump inhibitors, H2 receptor antagonists, or bismuth within recent 4 weeks of the tests were excluded. Clinical data for concurrent drug use and chronic diseases that may affect the accuracy of tests, such as atrophic gastritis, constipation, colon diverticulum, and diabetes mellitus, were recorded. The history of anti-H. pylori treatment (triple or quadruple regimens) was also collected. Subjects with no history of anti-H. pylori treatment before 13C-UBT and HpSA tests were regarded as the pre-treatment group. Those who were tested after anti-H. pylori treatment were assigned to the post-treatment group, irrespective of the frequency and/or outcome of the treatment. Also, gastric and colorectal polyps diagnosed by endoscopy within 3 years of HpSA detection were collected for the baseline comorbidity assessment. Patients with prior gastrointestinal cancer, overt gastrointestinal bleeding, and a history of gastrectomy were excluded. Subjects with intermediate HpSA results were also eliminated from the analysis.
This research was approved by the Ethics Committee of the Chinese PLA General Hospital.
2.2 13C-UBT detection
Helicobacter pylori infection was determined via the 13C-UBT. After fasting for over 8 hr, each subject drank a solution containing 75 mg of 13C-urea in 70 ml of water. Breath samples were collected before and 30 min after the ingurgitation of the water. Then, 13C-enrichment was detected using a 13C-breath test instrument (Fischer Analysen Instrumente GmbH). The results were defined as positive when the delta over baseline (DOB) was >4‰, calculated as the surplus of the isotopic ratio over the baseline isotopic ratio.
2.3 HpSA test
Fresh fecal samples were used for the analysis. A one-step chromatographic immunoassay, CerTest H. pylori Blister Test (CerTest Biotec S.L.), was applied for the analysis, following the manufacturer's instructions. Based on the condition of the control line and sample line, samples were categorized as positive, negative, or intermediate. All intermediate data were excluded from the final analysis.
2.4 Statistical analyses
Statistical analyses were performed using Statistical Package for Social Sciences version 25.0 (SPSS, Chicago, IL, USA). Sensitivity, specificity, PPV, and NPV with 95% confidence intervals (CI) were calculated by standard methods using 13C-UBT as the reference standard. Continuous variables are expressed as means ± standard deviation (SD). Categorical variables are expressed as n (%). The chi-square test was used to detect differences within categorical variables. A univariate analysis was performed for all variables, including age, comorbidities, and medications, via chi-square tests. A multivariate analysis was performed to determine independent factors for diagnostic efficiency using a binary logistic regression model. A p-value of less than 0.05 (two-sided) was regarded as statistically significant.
3 RESULTS
3.1 Demographic characteristics of participants
A total of 316 participants who underwent both 13C-UBT and HpSA tests were enrolled. Among them, 193 subjects were assigned to the pre-treatment group and 123 subjects were assigned to the post-treatment group. The mean ages of all participants and those in the pre-treatment and post-treatment groups were 77.8 ± 8.0 years, 77.2 ± 7.8 years, and 78.7 ± 8.3 years, respectively. The positive rate for 13C-UBT was 21.1% and that for HpSA was 16.5% (Table 1 and Table A1 in the Appendix A). Comorbidities in each group, such as atrophic gastritis, constipation, colorectal polyps, diabetes, hyperlipidemia, hypertension, and dementia, are listed in Table 1. A total of 72 (22.8%) participants suffered from constipation and 131 (41.5%) participants had colorectal polyps. Medications administered to the participants are summarized in Table A2 in the Appendix A.
| Characteristics | All (N = 316) | Pre-treatment (N = 193) | Post-treatment (N = 123) |
|---|---|---|---|
| Mean ± SD | |||
| Age (years) | 77.8 ± 8.0 | 77.2 ± 7.8 | 78.7 ± 8.3 |
| N (%) | |||
| 13C-UBT-positive | 67 (21.1) | 43 (22.3) | 24 (19.5) |
| HpSA test-positive | 52 (16.5) | 30 (15.5) | 22 (17.9) |
| Atrophic gastritis | 189 (59.8) | 115 (59.6) | 74 (60.2) |
| GERD | 53 (16.8) | 29 (15.0) | 24 (19.5) |
| Constipation | 72 (22.8) | 44 (22.8) | 28 (22.8) |
| Colon diverticulum | 34 (10.8) | 14 (7.3) | 20 (16.3) |
| Gastric polyps | 27 (8.5) | 19 (9.8) | 8 (6.5) |
| Colorectal polyps | 131 (41.5) | 76 (39.4) | 55 (44.7) |
| History of intestinal surgery | 8 (2.5) | 3 (1.6) | 5 (4.1) |
| Diabetes mellitus | 109 (34.5) | 70 (36.3) | 39 (31.7) |
| Hyperlipidemia | 49 (15.5) | 31 (16.1) | 18 (14.6) |
| Coronary heart disease | 166 (52.5) | 95 (49.2) | 71 (57.7) |
| Hypertension | 189 (59.8) | 113 (58.5) | 76 (61.8) |
| COPD | 77 (24.4) | 37 (19.2) | 40 (32.5) |
| Dementia | 10 (3.2) | 8 (4.1) | 2 (1.6) |
| Post-cerebral infarction | 64 (20.3) | 40 (20.7) | 24 (19.5) |
| Median (IQR) | |||
| Days between 13C-UBT and HpSA test (days) | 2 (1–4) | 2 (1–4) | 2 (1–4) |
- Abbreviations: COPD, chronic obstructive pulmonary disease; GERD, gastroesophageal reflux disease; HpSA, Helicobacter pylori stool antigen; IQR, interquartile range; N, number; SD, standard deviation; UBT, urea breath test.
3.2 Diagnostic efficacy of HpSA test
The performance of the HpSA test using 13C-UBT as a reference standard was analyzed. The median time between 13C-UBT and HpSA tests was 2 days (interquartile range 1–4 days). As shown in Figure 1 and Table A3 in the Appendix A, the accuracy of the HpSA test was 91.5% (95% CI: 87.8%–94.3%) for all participants, 91.2% (95% CI: 86.3%–94.8%) in the pre-treatment group, and 91.9% (95% CI: 85.6%–96.0%) in the post-treatment group. The specificities were 97.6% (95% CI: 94.6%–99.0%), 98.7% (95% CI: 94.8%–99.8%), and 96.0% (95% CI: 89.4%–98.7%) in these groups. However, the sensitivities were only 68.7% (95% CI: 56.0%–79.1%), 65.1% (95% CI: 49.0%–78.5%), and 75.0% (95% CI: 52.9%–89.4%) in these groups. The PPV was 88.5% (95% CI: 75.9%–95.2%) in all subjects, 93.3% (95% CI: 76.5%–98.8%) in the pre-treatment group, and 81.8% (95% CI: 59.0%–94.0%) in the post-treatment group, and the NPV was 92.0% (95% CI: 87.9%–94.9%), 90.8% (95% CI: 85.0%–94.6%), and 94.1% (95% CI: 87.0%–97.6%) in these groups. Intermediate results of HpSA tests and their potential influence on the diagnostic accuracy are listed in Tables A4 and A5 in the Appendix A.
3.3 Factors associated with HpSA sensitivity
We further investigated factors (comorbidities) that affect the sensitivity of the HpSA test. Univariate analysis indicated that the sensitivity of the HpSA test was significantly higher for participants over 78 years old than for younger participants (54.8% vs. 80.6%, p = 0.024), significantly lower in those with constipation than in those without (76.5% vs. 43.8%, p = 0.014), and higher in those with colorectal polyps than in those without (56.8% vs. 83.3%, p = 0.020). In the pre-treatment group, the sensitivity of the HpSA test was significantly lower in participants with constipation than in those without constipation (76.7% vs. 38.5%, p = 0.039). The sensitivity was significantly higher in participants with colorectal polyps than those without (45.0% vs. 82.6%, p = 0.010). Differences in these parameters were not observed in the post-treatment group (Table 2). Other comorbidities, such as colon diverticulum, a history of bowel surgery, diabetes, and hyperlipidemia, were not significantly correlated with HpSA sensitivity in this cohort. No medications were significantly associated with HpSA sensitivity in all groups (Table A6 in Appendix A).
| Factors | Subgroups | All | Pre-treatment | Post-treatment | |||
|---|---|---|---|---|---|---|---|
| Sensitivity | p | Sensitivity | p | Sensitivity | p | ||
| Age (years) | <78 | 54.8% | 0.024* | 54.5% | 0.137 | 55.6% | 0.224 |
| ≥78 | 80.6% | 76.2% | 86.7% | ||||
| Atrophic gastritis | − | 58.6% | 0.122 | 55.0% | 0.194 | 66.7% | 0.808 |
| + | 76.3% | 73.9% | 80.0% | ||||
| GERD | − | 67.8% | 0.995 | 64.1% | 1.000 | 75.0% | 1.000 |
| + | 75.0% | 75.0% | 75.0% | ||||
| Constipation | − | 76.5% | 0.014* | 76.7% | 0.039* | 76.2% | 0.722 |
| + | 43.8% | 38.5% | 66.7% | ||||
| Colon diverticulum | − | 68.9% | 1.000 | 64.3% | 1.000 | 78.9% | 0.772 |
| + | 66.7% | 100.0% | 60.0% | ||||
| Gastric polyps | − | 68.3% | 1.000 | 65.0% | 1.000 | 73.9% | 1.000 |
| + | 75.0% | 66.7% | 100.0% | ||||
| Colorectal polyps | − | 56.8% | 0.020* | 45.0% | 0.010 * | 70.6% | 0.795 |
| + | 83.3% | 82.6% | 85.7% | ||||
| History of intestinal surgery | − | 68.2% | 1.000 | 65.1% | NULL | 73.9% | 1.000 |
| + | 100.0% | NULL | 100.0% | ||||
| Diabetes mellitus | − | 69.2% | 0.905 | 68.2% | 0.666 | 70.6% | 0.795 |
| + | 67.9% | 61.9% | 85.7% | ||||
| Hyperlipidemia | − | 73.2% | 0.145 | 71.4% | 0.160 | 76.2% | 1.000 |
| + | 45.5% | 37.5% | 66.7% | ||||
| Coronary heart disease | − | 69.0% | 0.962 | 73.7% | 0.294 | 60.0% | 0.339 |
| + | 68.4% | 58.3% | 85.7% | ||||
| Hypertension | − | 64.3% | 0.513 | 66.7% | 0.856 | 60.0% | 0.339 |
| + | 71.8% | 64.0% | 85.7% | ||||
| COPD | − | 63.8% | 0.192 | 62.5% | 0.805 | 66.7% | 0.465 |
| + | 80.0% | 72.7% | 88.9% | ||||
| Dementia | − | 68.8% | 1.000 | 65.0% | 1.000 | 75.0% | NULL |
| + | 66.7% | 66.7% | NULL | ||||
| Post-cerebral infarction | − | 65.3% | 0.329 | 61.3% | 0.625 | 72.2% | 1.000 |
| + | 77.8% | 75.0% | 83.3% | ||||
- Abbreviations: COPD, chronic obstructive pulmonary disease; GERD, gastroesophageal reflux disease; HpSA, Helicobacter pylori stool antigen.
- * p < 0.05.
To identify the most important covariate for HpSA sensitivity, various factors including age, constipation, and colorectal polyps were subjected to multivariate regression analysis. Both constipation and colorectal polyps were independent factors for the sensitivity of the HpSA test in all participants and the pre-treatment group. All summary statistics are summarized in Table 3.
| Groups | Factors | Regression coefficient | SE for regression coefficient | p | OR (95% CI) |
|---|---|---|---|---|---|
| All | Constipation | −2.01 | 0.74 | 0.007* | 0.134 (0.032–0.570) |
| Colorectal polyps | 1.87 | 0.72 | 0.009* | 6.492 (1.591–26.482) | |
| Pre-treatment | Constipation | −2.16 | 0.89 | 0.016* | 0.115 (0.020–0.666) |
| Colorectal polyps | 2.21 | 0.87 | 0.011* | 9.095 (1.656–49.955) |
- Abbreviations: CI, confidence interval; HpSA, Helicobacter pylori stool antigen; OR, odds ratio; SE, standard error.
- * p < 0.05.
A subgroup analysis showed that the accuracy of the HpSA test in patients with constipation was lower than that in patients without constipation (94.3% vs. 81.9%) for all participants (Table A7 in Appendix A). A similar tendency was found in the pre-treatment group (95.3% vs. 77.3%) (Table A8 in Appendix A). The accuracy of the HpSA test in patients with colorectal polyp was higher than that in non-colorectal polyp counterparts (88.1% vs. 96.2%) for all participants (Table A7 in the Appendix A) and the pre-treatment group (88.9% vs. 94.7%) (Table A8 in the Appendix A).
4 DISCUSSION
Monoclonal HpSA test is considered a precise, noninvasive method for the diagnosis of H. pylori infection and proof of H. pylori eradication (Gisbert, de la Morena, & Abraira, 2006; McNicholl et al., 2019). It is approved by the FDA of the United States and is recommended by clinical guidelines as a substitute for invasive diagnostic methods (Malfertheiner et al., 2017). The HpSA test only requires fresh stool samples and therefore is particularly useful in relatively old patients and especially in individuals who are not able to expire air completely or who cannot swallow. Furthermore, the HpSA test has higher precision than UBT in patients with a history of subtotal gastrectomy (Costa et al., 2001). Data for the sensitivity and specificity of ICA-based HpSA in asymptomatic older subjects are lacking. Using the 13C-UBT as a reference standard, our results showed that ICA-based HpSA has a very high specificity (all: 97.6%, pre-treatment: 98.7%, post-treatment: 96.0%) but a relatively low sensitivity (all: 68.7%, pre-treatment: 65.1%, post-treatment: 75.0%), with an accuracy of greater than 91% in each group. The results were comparable to those of a previous study of hospitalized elderly patients (≥65 years old), in which the sensitivity and specificity of the Premier Platinum HpSA test (EIA-based HpSA) in untreated patients were 76% and 93%, respectively (Inelmen, Gasparini, & Sergi, 2005). Similar results were reported in a study involving 122 elderly hospitalized patients (Inelmen et al., 2004). These data indicated that the sensitivity of the HpSA test could be inferior to those of other tests in elderly individuals.
Some studies have suggested that H. pylori shedding decreases with an increase in the chronicity of infection (Haggerty, Perry, Sanchez, Perez-Perez, & Parsonnet, 2005), which is commonly observed in the elderly population. The prolonged passage of bacteria into the colon owing to chronic constipation may also lead to the degradation of H. pylori antigens (Monteiro, Gras, Vidal, Cabrita, & Mégraud, 2001), thereby decreasing the accuracy of the HpSA test. Consistent with these previous results, our univariate and multivariate analyses revealed a significantly lower sensitivity of the HpSA test in subjects with constipation than in those without constipation in the pre-treatment group. However, we found no correlation between HpSA sensitivity and drugs with the potential to affect passage through the colon, such as opioid analgesics.
We noted that colorectal polyps were closely related to the sensitivity of the HpSA test (88.9% in participants with colorectal polyps vs. 50.0% in participants without colorectal polyps). Helicobacter pylori infection has been identified as an independent risk factor for colorectal polyps and colonic adenomas, especially in cases of advanced or multiple lesions (Dong, Guo, & Yang, 2019; Nam et al., 2017); we detected a correlation between H. pylori infection and colorectal polyps in the pre-treatment group but not in the post-treatment group or the whole cohort (Table A9 in the Appendix A). We did not find an association between polyps and constipation in the pre-treatment group (Table A10 in Appendix A). Large prospective studies are needed for further investigation of the association between colorectal polyps and HpSA sensitivity in the elderly.
Low sensitivity of the polyclonal HpSA test in the post-treatment setting has been reported (Gisbert & Pajares, 2004b). However, there is evidence that the HpSA test using monoclonal antibodies shows superior sensitivity to those of tests using polyclonal antibodies, particularly in the post-treatment setting (Gisbert et al., 2006). We achieved an accuracy rate exceeding 91% in both pre- and post-treatment groups by using ICA, consistent with previous reports (Vaira et al., 2000). Our stringent inclusion criteria may explain the high accuracy obtained in both the pre- and post-treatment groups. In this study, factors with the potential to affect the accuracy of 13C-UBT or HpSA, such as proton-pump inhibitors, antibiotics, bismuth therapy (Calvet et al., 2002; Gisbert & Pajares, 2001; Grino et al., 2003; Inelmen et al., 2005), a history of gastrectomy, and overt gastrointestinal bleeding, were excluded. Cases with “indeterminate results” were also excluded. Furthermore, the 13C-UBT and HpSA tests were performed on the same day or with an interval of no longer than 7 days to minimize the error caused by variation in detection times. Finally, we recruited only asymptomatic elderly subjects who underwent the tests for health checkup purposes to minimize the influence of active and/or severe diseases.
There were several limitations to this study. First, 13C-UBT, believed to be an ideal noninvasive assay, was chosen as the only reference standard (Best et al., 2018). According to the literature, the false-negative rate of 13C-UBT could be elevated in elderly individuals (Salles-Montaudon et al., 2001). A combination of invasive tests, such as histological or culture data, would be a more effective reference standard. Also, the sample size was relatively small and was limited to male subjects. Sample size calculation was performed based on the following settings: the prevalence of H. pylori infection (around 25%) in the cohort, previously reported sensitivity (76%) and specificity (93%) values for the HpSA test in the elderly (Inelmen et al., 2005), and a two-sided α level of 0.05. We noticed that only the whole study cohort matched the sample size requirement. Although no study has reported a gender difference in noninvasive detection efficiency, further studies of both male and female subjects will broaden our knowledge in this field. Moreover, participants were in a relatively higher-than-average socioeconomic status, as evidenced by their utilization of a regular health check with a low prevalence (22.3%) of H. pylori infection, compared with a reported prevalence in Beijing, China, in the general population of as high as 47.0% (Hooi et al., 2017). Hence, the generalizability of the results of this study to the whole elderly population should be performed with caution. Lastly, we cannot confirm the causality between the parameters identified, such as colorectal polyps, and HpSA sensitivity, as this is an observational study.
5 CONCLUSIONS
In an observational study of an elderly male cohort, we revealed that HpSA achieves high accuracy and specificity but suboptimal sensitivity in both pre- and post-treatment groups when using 13C-UBT as a reference standard. Our findings show that ICA-based HpSA is accurate for the diagnosis of H. pylori infection in the elderly. We found that comorbidities, such as constipation and colorectal polyps, can affect the sensitivity of HpSA. Owing to the lower sensitivity of the HpSA test, caution should be taken when applying this test to elderly patients with constipation.
ACKNOWLEDGMENTS
We would like to thank Prof. Wai K Leung (University of Hong Kong) for valuable comments and helpful discussion. This study was supported by Healthcare Research Projects, China PLA (grant number 18BJZ22), and the National Clinical Research Center for Geriatric Diseases (grant number NCRCG-PLAGH-2019015).
CONFLICT OF INTEREST
None declared.
AUTHOR CONTRIBUTIONS
Yingjie Han: Data curation (lead); formal analysis (lead); project administration (supporting); writing – original draft (lead); writing – review & editing (supporting). Wei Dai: Investigation (equal). Fansen Meng: Investigation (equal). Xueyang Gan: Investigation (equal). Miao Liu: Formal analysis (supporting). Xinli Deng: Investigation (supporting); resources (supporting). Yuan Li: Investigation (supporting); resources (supporting). Gangshi Wang: Conceptualization (lead); Data curation (supporting); investigation (supporting); project administration (lead); resources (lead); supervision (lead); writing – review & editing (lead).
ETHICS STATEMENT
This retrospective study complies with the Declaration of Helsinki and was following standards of the ethical committee of the Chinese PLA General Hospital. Because data collection was based on retrospective searches of electronic medical records and patient identities were not disclosed, consent was not available and was not required according to the ethics committee of Chinese PLA General Hospital.
Appendix A
| Groups | HpSA test | 13C-UBT | ||
|---|---|---|---|---|
| + | − | Total | ||
| All participants | + | 46 | 6 | 52 |
| − | 21 | 243 | 264 | |
| Total | 67 | 249 | 316 | |
| Pre-treatment | + | 28 | 2 | 30 |
| − | 15 | 148 | 163 | |
| Total | 43 | 150 | 193 | |
| Post-treatment | + | 18 | 4 | 22 |
| − | 6 | 95 | 101 | |
| Total | 24 | 99 | 123 | |
- Abbreviations: HpSA, Helicobacter pylori stool antigen; UBT, urea breath test.
| Medications | All (N = 316) | Pre-treatment (N = 193) | Post-treatment (N = 123) |
|---|---|---|---|
| N (%) | |||
| Prokinetic agents | 18 (5.7) | 11 (5.7) | 7 (5.7) |
| Opioid analgesics | 44 (13.9) | 22 (11.4) | 22 (17.9) |
| Prebiotics or probiotics | 37 (11.7) | 24 (12.4) | 13 (10.6) |
| Digestive enzyme | 22 (7) | 12 (6.2) | 10 (8.1) |
| Antiplatelet agents | 40 (12.7) | 28 (14.5) | 12 (9.8) |
| Antihypertensive agents | 189 (59.8) | 113 (58.5) | 76 (61.8) |
| Lipid-lowering agents | 57 (18) | 44 (22.8) | 13 (10.6) |
| α-glucosidase inhibitor | 14 (4.4) | 12 (6.2) | 2 (1.6) |
| Groups | Accuracy (95% CI) | Sensitivity (95% CI) | Specificity (95% CI) | PPV (95% CI) | NPV (95% CI) |
|---|---|---|---|---|---|
| All participants | 91.5% (87.8%–94.3%) | 68.7% (56.0%–79.1%) | 97.6% (94.6%–99.0%) | 88.5% (75.9%–95.2%) | 92.0% (87.9%–94.9%) |
| Pre-treatment | 91.2% (86.3%–94.8%) | 65.1% (49.0%–78.5%) | 98.7% (94.8%–99.8%) | 93.3% (76.5%–98.8%) | 90.8% (85.0%–94.6%) |
| Post-treatment | 91.9% (85.6%–96.0%) | 75.0% (52.9%–89.4%) | 96.0% (89.4%–98.7%) | 81.8% (59.0%–94.0%) | 94.1% (87.0%–97.6%) |
- Abbreviations: CI, confidence interval; HpSA, Helicobacter pylori stool antigen; NPV, negative predictive value; PPV, positive predictive value; UBT, urea breath test.
- a Excluding intermediate results for the HpSA test.
| Groups | Accuracy (95% CI) | Sensitivity (95% CI) | Specificity (95% CI) | PPV (95% CI) | NPV (95% CI) |
|---|---|---|---|---|---|
| All participants | 87.7% (87.7%–87.8%) | 70.4% (59.8%–81.0%) | 92.4% (89.2%–95.6%) | 71.4% (60.8%–82.0%) | 92.0% (88.8%–95.3%) |
| Pre-treatment | 87.3% (87.2%–87.4%) | 67.4% (53.8%–80.9%) | 93.1% (89.1%–97.0%) | 73.8% (60.5%–87.1%) | 90.8% (86.4%–95.2%) |
| Post-treatment | 88.4% (88.2%–88.5%) | 76.0% (59.3%–92.7%) | 91.3% (85.9%–96.7%) | 67.9% (50.6%–85.2%) | 94.1% (89.4%–98.7%) |
- Abbreviations: CI, confidence interval; HpSA, Helicobacter pylori stool antigen; NPV, negative predictive value; PPV, positive predictive value; UBT, urea breath test.
- a Treating intermediate results for the HpSA test as positive results.
| Groups | Accuracy (95% CI) | Sensitivity (95% CI) | Specificity (95% CI) | PPV (95% CI) | NPV (95% CI) |
|---|---|---|---|---|---|
| All participants | 90.7% (90.7%–90.8%) | 64.8% (53.7%–75.9%) | 97.7% (95.9%–99.5%) | 88.5% (79.8%–97.1%) | 91.1% (87.8%–94.5%) |
| Pre-treatment | 90.2% (90.2%–90.3%) | 60.9% (46.8%–75.0%) | 98.7% (97.0%–100.0%) | 93.3% (84.4%–100.0%) | 89.7% (85.2%–94.2%) |
| Post-treatment | 91.5% (91.4%–91.6%) | 72.0% (54.4%–89.6%) | 96.2% (92.5%–99.8%) | 81.8% (65.7%–97.9%) | 93.5% (88.8%–98.1%) |
- Abbreviations: CI, confidence interval; HpSA, Helicobacter pylori stool antigen; NPV, negative predictive value; PPV, positive predictive value; UBT, urea breath test.
- a Treating intermediate results of the HpSA test as negative results.
| Factors | Subgroups | All | Pre-treatment | Post-treatment | |||
|---|---|---|---|---|---|---|---|
| Sensitivity | p | Sensitivity | p | Sensitivity | p | ||
| Prokinetic agents | − | 68.9% | 1.000 | 63.2% | 0.807 | 78.3% | 0.250 |
| + | 66.7% | 80.0% | 0.0% | ||||
| Opioid analgesics | − | 66.1% | 0.413 | 63.2% | 0.807 | 71.4% | 0.546 |
| + | 87.5% | 80.0% | 100.0% | ||||
| Prebiotics or probiotics | − | 67.8% | 0.995 | 62.2% | 0.584 | 77.3% | 0.446 |
| + | 75.0% | 83.3% | 50.0% | ||||
| Digestive enzyme | − | 69.8% | 0.784 | 65.9% | 1.000 | 77.3% | 0.446 |
| + | 50.0% | 50.0% | 50.0% | ||||
| Antiplatelet agents | − | 69.0% | 1.000 | 63.9% | 1.000 | 77.3% | 0.446 |
| + | 66.7% | 71.4% | 50.0% | ||||
| Antihypertensive agents | − | 64.3% | 0.513 | 66.7% | 0.856 | 60.0% | 0.339 |
| + | 71.8% | 64.0% | 85.7% | ||||
| Lipid-lowering agents | − | 68.5% | 1.000 | 64.5% | 1.000 | 73.9% | 1.000 |
| + | 69.2% | 66.7% | 100.0% | ||||
| α-glucosidase inhibitor | − | 70.5% | 0.568 | 67.6% | 0.707 | 75.0% | NULL |
| + | 50.0% | 50.0% | NULL | ||||
- Abbreviation: HpSA, Helicobacter pylori stool antigen.
| Subgroup | HpSA test | 13C-UBT | Accuracy (95% CI) | Sensitivity (95% CI) | Specificity (95% CI) | PPV (95% CI) | NPV (95% CI) | ||
|---|---|---|---|---|---|---|---|---|---|
| + | − | Total | |||||||
| Non-constipation | + | 39 | 2 | 41 | 94.3% (94.2%–94.3%) | 76.5% (64.8%–88.1%) | 99.0% (97.5%–100%) | 95.1% (88.5%–100%) | 94.1% (90.8%–97.3%) |
| − | 12 | 191 | 203 | ||||||
| Total | 51 | 193 | 244 | ||||||
| Constipation | + | 7 | 4 | 11 | 81.9% (81.5%–82.3%) | 43.8% (19.4%–68.1%) | 92.9% (86.1%–99.6%) | 63.6% (35.2%–92.1%) | 85.2% (76.3%–94.1%) |
| − | 9 | 52 | 61 | ||||||
| Total | 16 | 56 | 72 | ||||||
| Non-colorectal polyps | + | 21 | 6 | 27 | 88.1% (88.0%–88.2%) | 56.8% (40.8%–72.7%) | 95.9% (92.8%–99.1%) | 77.8% (62.1%–93.5%) | 89.9% (85.2%–94.6%) |
| − | 16 | 142 | 158 | ||||||
| Total | 37 | 148 | 185 | ||||||
| Colorectal polyps | + | 25 | 0 | 25 | 96.2% (96.1%–96.2%) | 83.3% (70.0%–96.7%) | 100.0% (100%–100%) | 100.0% (100%–100%) | 95.3% (91.2%–99.3%) |
| − | 5 | 101 | 106 | ||||||
| Total | 30 | 101 | 131 | ||||||
- Abbreviations: CI, confidence interval; HpSA, Helicobacter pylori stool antigen; NPV, negative predictive value; PPV, positive predictive value; UBT, urea breath test.
- a 13C-UBT served as the gold standard.
| Subgroup | HpSA test | 13C-UBT | Accuracy (95% CI) | Sensitivity (95% CI) | Specificity (95% CI) | PPV (95% CI) | NPV (95% CI) | ||
|---|---|---|---|---|---|---|---|---|---|
| + | − | Total | |||||||
| Non-constipation | + | 23 | 0 | 23 | 95.3% (90.6%–98.1%) | 76.7% (57.3%–89.4%) | 100.0% (96.1%–100.0%) | 100.0% (82.2%–100.0%) | 94.4% (88.5%–97.5%) |
| − | 7 | 119 | 126 | ||||||
| Total | 30 | 119 | 149 | ||||||
| Constipation | + | 5 | 2 | 7 | 77.3% (62.2%–88.5%) | 38.5% (15.1%–98.9%) | 93.5% (77.2%–98.9%) | 71.4% (30.3%–98.9%) | 78.4% (61.3%–98.9%) |
| − | 8 | 29 | 37 | ||||||
| Total | 13 | 31 | 44 | ||||||
| Non-colorectal polyps | + | 9 | 2 | 11 | 88.9% (81.7%–93.9%) | 45.0% (23.8%–68.0%) | 97.9% (92.0%–99.6%) | 81.8% (47.8%–96.8%) | 89.6% (81.8%–94.5%) |
| − | 11 | 95 | 106 | ||||||
| Total | 20 | 97 | 117 | ||||||
| Colorectal polyps | + | 19 | 0 | 19 | 94.7% (87.1%–98.5%) | 82.6% (60.5%–94.3%) | 100.0% (91.6%–100.0%) | 100.0% (79.1%–100.0%) | 93.0% (82.2%–97.7%) |
| − | 4 | 53 | 57 | ||||||
| Total | 23 | 53 | 76 | ||||||
- Abbreviations: CI, confidence interval; HpSA, Helicobacter pylori stool antigen; NPV, negative predictive value; PPV, positive predictive value; UBT, urea breath test.
- a 13C-UBT served as the reference standard.
| Groups | Subgroups | 13C-UBT-negative | 13C-UBT-positive | χ2 | p |
|---|---|---|---|---|---|
| All participants | Non-colorectal polyps | 148 | 37 | 0.386 | 0.534 |
| Colorectal polyps | 101 | 30 | |||
| Pre-treatment | Non-colorectal polyps | 97 | 20 | 4.614 | 0.032* |
| Colorectal polyps | 53 | 23 | |||
| Post-treatment | Non-colorectal polyps | 51 | 17 | 2.916 | 0.088 |
| Colorectal polyps | 48 | 7 |
- Abbreviation: 13C-UBT, 13C-urea breath test.
- * p < 0.05.
| Groups | Subgroups | Colorectal polyps N (%) | χ2 | p |
|---|---|---|---|---|
| All participants | Non-constipation | 21 (41.2) | 1.119 | 0.290 |
| Constipation | 9 (56.3) | |||
| Pre-treatment | Non-constipation | 16 (53.3) | 0.001 | 0.975 |
| Constipation | 7 (53.8) |
- Abbreviation: UBT, urea breath test.
Open Research
DATA AVAILABILITY STATEMENT
All primary data obtained in this study excluding information related to participant identities are shown in Supplementary Table A11 available in the Zenodo repository (https://doi.org/10.5281/zenodo.3871777).
