The performance of diagnostic tests in intervention trials of Helicobacter pylori (H.pylori) eradication is crucial, since even minor inaccuracies can have major impact. To determine the cut-off point for 13C-urea breath test (13C-UBT) and to assess if it can be further optimized by serologic testing, mathematic modeling, histopathology and serologic validation were applied. A finite mixture model (FMM) was developed in 21,857 subjects, and an independent validation by modified Giemsa staining was conducted in 300 selected subjects. H.pylori status was determined using recomLine H.pylori assay in 2,113 subjects with a borderline 13C-UBT results. The delta over baseline-value (DOB) of 3.8 was an optimal cut-off point by a FMM in modelling dataset, which was further validated as the most appropriate cut-off point by Giemsa staining (sensitivity = 94.53%, specificity = 92.93%). In the borderline population, 1,468 subjects were determined as H.pylori positive by recomLine (69.5%). A significant correlation between the number of positive H.pylori serum responses and DOB value was found (rs = 0.217, P < 0.001). A mathematical approach such as FMM might be an alternative measure in optimizing the cut-off point for 13C-UBT in community-based studies, and a second method to determine H.pylori status for subjects with borderline value of 13C-UBT was necessary and recommended.

Charles University Central Military Hospital Prague Ovocný trh 3 5 Prague 11636 Czech Republic

German Centre of Infection Research partner site Munich Munich Germany

Healthy Bureau of Linqu County Shandong China

Institute of Pathology Klinikum Bayreuth Preuschwitzer Str 101 95445 Bayreuth Germany

International Digestive Cancer Alliance 81541 Munich Germany

Key Laboratory of Carcinogenesis and Translational Research Department of Cancer Epidemiology Peking University Cancer Hospital and Institute 52 Fu cheng Road Hai dian District Beijing 100142 China

Mikrogen GmbH Floriansbogen 2 4 Neuried Munich 82061 Germany

Technische Universität München Klinikum rechts der Isar Trogerstr 30 81675 Munich Germany

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