Association of epithelial and subepithelial <i>H. pylori</i> distribution detected by immunohistochemistry in gastric biopsies and clinical outcomes of patients receiving proton pump inhibitors

Studies have shown that <i>Helicobacter pylori</i> (<i>H. pylori)</i> can penetrate both the epithelium and subepithelium, which may lead to underdiagnosis. Rod-shaped <i>H. pylori</i> can transform into coccoid forms during proton pump inhibitor (PPI) therapy. However, the relationships among PPI use, bacterial invasiveness and clinical outcomes remain unclear. In the present retrospective study, the relationships among PPI use, <i>H. pylori</i> distribution patterns and clinical outcomes were investigated. Gastric tissue biopsies obtained between October and December 2022 were retrospectively studied using BioGenex immunohistochemical antibodies. <i>H. pylori</i> distribution was graded on the basis of surface epithelial and subepithelial locations. The overall pattern of <i>H. pylori</i> infection was determined from the grade and pattern of distribution. Data from patients with and without PPI use were compared. Among the 255 patients, those with and without PPI use had significantly different isolated epithelial patterns. Multivariate analysis revealed a positive correlation between PPI use and the isolated surface epithelial pattern and an inverse correlation with the isolated subepithelial pattern. Survival analysis revealed that the isolated subepithelial pattern was associated with the poorest clinical outcomes. Furthermore, eradication rates were lower in patients with the isolated subepithelial pattern than in patients with isolated surface epithelial pattern or other mixed patterns. The results of the present study suggested that PPI use altered the gastric mucosal microenvironment and bacterial biology. The presence of subepithelial <i>H. pylori</i> could be incorporated into pathological reports as ancillary studies along with the updated Sydney reporting system and could be incorporated into future clinical management.