The necessity and appropriate range of the diagnostic “gray zone” of (13)C-urea breath test

BACKGROUND: The (13)C-urea breath test ((13)C-UBT) is preferred for non-invasive detection of Helicobacter pylori (H. pylori); however, its accuracy drops when results fall between 2‰ and 6‰ (called the gray zone). This study aimed to evaluate the accuracy of (13)C-UBT (cut-off point 4‰) between 2‰ and 6‰, find a more appropriate gray zone, and identify the factors influencing (13)C-UBT. METHODS: Patients with (13)C-UBT results 2‰–6‰, over an eight-year period, were studied. H. pylori infection was diagnosed if patients were positive for either Warthin–Starry staining or quantitative real-time polymerase chain reaction (real-time PCR), and excluded if both were negative. Accuracy of (13)C-UBT under different cut-off points was calculated, and the factors affecting (13)C-UBT were analyzed. RESULTS: A total of 208 patients were included, of whom 129 were H. pylori–positive. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of (13)C-UBT were 71.32%, 83.54%, 64.08%, and 87.62%, respectively. When the cut-off point was changed to 2.15‰, the NPV of (13)C-UBT reached a maximum (76.47%); when the cut-off point was changed to 4.95‰, PPV reached its maximum (93.22%). Therefore, the original gray zone (2‰–6‰) was adjusted to 2‰–4.95‰. Gastric antral intestinal metaplasia (OR = 3.055, 95% CI: 1.003–9.309) was an independent risk factor for false-negative (13)C-UBT. CONCLUSIONS: Accuracy of (13)C-UBT over 2‰–6‰ was poor, and the gray zone was changed to 2‰–4.95‰. (13)C-UBT results over 2‰–4.95‰ should be interpreted with caution during mass screening of H. pylori, especially for patients with gastric antral intestinal metaplasia.