Occult H. pylori infection partially explains 'false-positive' results of (13)C-urea breath test

Abstract

Background: In a previous study, UBiT-100 mg, (Otsuka, Spain), a commercial (13)C-urea breath test omitting citric acid pre-treatment, had a high rate of false-positive results; however, it is possible that UBiT detected low-density 'occult' infection missed by other routine reference tests. We aimed to validate previous results in a new cohort and to rule out the possibility that false-positive UBiT were due to an 'occult' infection missed by reference tests.

Methods: Dyspeptic patients (n = 272) were prospectively enrolled and UBiT was performed, according to the manufacturer's recommendations. Helicobacter pylori infection was determined by combining culture, histology and rapid urease test results. We calculated UBiT sensitivity, specificity, positive and negative predictive values (with 95% CI). In addition, we evaluated 'occult' H. pylori infection using two previously-validated polymerase chain reaction (PCR) methods for urease A (UreA) and 16 S sequences in gastric biopsies. We included 44 patients with a false-positive UBiT, and two control groups of 25 patients each, that were positive and negative for all H. pylori tests.

Results: UBiT showed a false-positive rate of 17%, with a specificity of 83%. All the positive controls and 12 of 44 patients (27%) with false-positive UBiT were positive for all two PCR tests; by contrast, none of our negative controls had two positive PCR tests.

Conclusions: UBiT suffers from a high rate of false-positive results and sub-optimal specificity, and the protocol skipping citric acid pre-treatment should be revised; however, low-density 'occult' H. pylori infection that was undetectable by conventional tests accounted for around 25% of the 'false-positive' results.

Keywords: Bacterial infection; Helicobacter pylori; diagnostic tests; false positive results; sensitivity; specificity; urea breath tests.

Figure 1.

Distribution of UBT values in patients with positive and negative H. pylori infection according to the Gold Standard. H. pylori: the bacteria Helicobacter pylori; UBiT: the specific name given to a commercial UBT; UBT: urea breath test

Figure 2.

STARD diagram depicting the flow of patients and the results of the analysis. Values are calculated for UBiT Delta cut-offs of 2.5‰ and 8.5‰. GS +: positive gold standard, GS –: negative gold standard; STARD: Standards for Reporting of Diagnostic Accuracy; UBiT: a specific commercial UBT; UBT: urea breath test

Figure 3.

Number of PCR positive tests in positive and negative controls and in ‘false-positive’ UBiT results. The 25 positive controls with all positive tests (UBiT, RUT, histology and culture) were all positive for the two PCRs, whereas none of the 25 negative controls had two positive PCR tests; also, 27% of patients with a ‘false-positive’ UBiT were positive for the two PCRs. PCR: polymerase chain reaction; RUT: Rapid Urease Test; UBiT: name of the commercial urea breath test used.