Proton Pump Inhibitor Challenge to Confirm Diagnosis of Atrophic Gastritis of the Stomach: A Proposal

Background & Aims: Chronic atrophic gastritis (CAG) is a known precancerous condition that can lead to the development of gastric cancer (GC). Low serum pepsinogen (PG) I levels have been proposed as a non-invasive marker for chronic atrophic gastritis of the stomach body, but the adequate upper cut-off for diagnosis remains controversial, as values ranging from 30 to 50 mcg/L are currently considered as a “grey zone”. We aimed to identify patients with chronic atrophic gastritis (CAG) of the stomach body amongst subjects with PG-I levels ranging between 30 and 50 mcg/L by means of a proton pump inhibitor (PPI) challenge. Methods: We selected 102 patients with baseline PG-I <60 mcg/L in whom upper gastrointestinal endoscopy with protocol biopsies staged according to OLGA system had been performed. Subsequently, all patients underwent a PPI challenge (consisting of PG-I testing after taking Esomeprazole 40 mg daily for 1 week). This population was divided into 5 groups according to PG-I levels: group A (PG-I< 30 mcg/L); group B (PG-I: 31-35 mcg/L); group C (PG-I: 36-40 mcg/L); group D (PG-I: 41-50 mcg/L); group E (PG-I: 51-60 mcg/L). By using the ROC curve, a cut-off of 30% increase from baseline PG-I was chosen. Results: A statistically significant relationship between PG-I levels and OLGA staging was found, being 100% in the group of PG-I < 30mcg/L. Based on the value of the cut-off of 30% (calculated by ROC curve) corresponding to the delta increase between PG-I baseline value and after a one-week full dose of PPI, the positive predictive value was 95%, the negative predictive value 86%, the sensitivity 83% and the specificity 96%. Conclusions: The use of the PPI challenge allows to identify subjects with CAG showing pepsinogen I values ranging between 30 and 50 mcg/L.