Published online Jul 21, 2018. doi: 10.3748/wjg.v24.i27.3021
Peer-review started: April 28, 2018
First decision: June 11, 2018
Revised: June 12, 2018
Accepted: June 27, 2018
Article in press: June 27, 2018
Published online: July 21, 2018
Diagnostic approaches for Helicobacter pylori (H. pylori) infection include invasive and non-invasive testing. The non-invasive 13C-urea breath test and stool monoclonal antigen test have high accuracy for diagnosing the infection, although the stool test has low acceptability in some contexts and needs local validation. The need for upper endoscopy is a limitation to the use of invasive tests. Molecular tests are promising approaches for diagnosing H. pylori infection, due to the added advantage of identifying bacterial DNA mutations associated with antibiotic resistance.
The application of molecular diagnostic tests on gastric biopsy samples is limited by the need for invasive endoscopic procedure. Thus, the non-invasive application of these tests on fecal samples is gaining increasing interest. An accurate non-invasive molecular test may guide first-line eradicating treatments with the potential advantages of increasing bacterial eradication rates and reducing the development of H. pylori resistance to antibiotics. However, existing studies on molecular tests for H. pylori detection in stools show suboptimal quality.
We aimed to assess the accuracy of a new non-invasive molecular test, the THD fecal test, for the diagnosis of H. pylori infection, using 13C-urea breath test as the reference standard. Additionally, we estimated the point prevalence of H. pylori DNA mutations conferring resistance to clarithromycin and levofloxacin.
We conducted a prospective two-center diagnostic test accuracy study. We enrolled consecutive people ≥ 18 years old without previous diagnosis of H. pylori infection, referred for dyspepsia between February and October 2017. At enrollment, all participants underwent 13C-urea breath test. Participants aged over 50 years were scheduled to undergo upper endoscopy with histology. Participants collected stool samples 1-3 d after enrollment for the THD fecal test. The detection of bacterial 23S rRNA subunit gene indicated H. pylori infection. We also used the index diagnostic test to examine mutations conferring resistance to clarithromycin and levofloxacin. Independent investigators analyzed the index test and reference standard test results blinded to the other test findings, participants’ information and histology results. We estimated diagnostic accuracy parameters, together with their 95% confidence intervals. The novelty of our research methods included an a priori sample size, a prospective enrollment of consecutive participants, and the blindingof outcome assessors. This approach increased the certainty of our findings.
Out of 294 participants, 95 (32.3%) had a positive 13C-urea breath test. Four (1.4%) participants withdrew from the study after the enrollment visit. In the 290 participants who completed the study, the THD fecal test sensitivity was 90.2% (CI: 84.2%-96.3%), specificity 98.5% (CI: 96.8%-100%), positive predictive value 96.5% (CI: 92.6%-100%), negative predictive value 95.6% (CI: 92.8%-98.4%), accuracy 95.9% (CI: 93.6%-98.2%), positive likelihood ratio 59.5 (CI: 19.3-183.4), negative likelihood ratio 0.10 (CI: 0.05-0.18). Out of 83 H. pylori infected participants identified with the THD fecal test, 27 (32.5%) had bacterial strains resistant to clarithromycin, 3 (3.6%) to levofloxacin, and 4 (4.8%) to both antibiotics.
Our results indicate that the THD fecal test has high diagnostic accuracy for the non-invasive diagnosis of H. pylori infection in patients with dyspeptic symptoms, while enabling identification of bacterium resistance to clarithromycin and levofloxacin. The certainty of our findings is based on the rigorous methodological approach used in the assessment of the THD fecal test diagnostic performance. THD fecal testing may inform clinical decision-making and guide individualized therapies to eradicate H. pylori infection.
The spread of H. pylori resistance to antibiotics has prompted the investigation of the efficacy of antibiotic susceptibility-guided therapies. THD fecal testing may assist in the conduct of randomized trials to evaluate the benefits and harms of tailored eradication strategies in first-line.