Introduction: The newly developed vonoprazan (a potassium-competitive acid blocker) has a greater ability to suppress gastric acid production than convention proton pump inhibitors (PPIs). The objective of the present study was to determine how vonoprazan influences the pathogenesis of refractory gastroesophageal reflux disease (GERD) in clinical practice. Methods: Between March 2013 and November 2018, a total of 73 refractory GERD patients (34 in the conventional PPI group versus 39 in the vonoprazan group) were enrolled in this retrospective study. We then compared the underlying disease conditions between the 2 groups, examined by high-resolution manometry and multichannel intraluminal impedance/pH (MII-pH) monitoring. Results: There was a significant difference in the proportion of underlying disease conditions, including erosive esophagitis, non-erosive reflux disease, reflux hypersensitivity, functional heartburn and oesophageal motility disorder (EMD), between the conventional PPI (6, 14, 23, 40 and 17% respectively) and vonoprazan groups (0, 0, 10, 49, and 41% respectively; p < 0.01). No cases of acid-related GERD were observed in the vonoprazan group. When the EMD patients were excluded, the lower oesophageal acid exposure time of the vonoprazan group (0.1% [0.0–0.5%], n = 23) was significantly lower than that of the conventional PPI group (0.35% [0.1–3.9%], n = 28; p < 0.05), and the gastric pH <4 holding time of the vonoprazan group (7.7% [0.7–34.5%]) was also significantly lower than that of the conventional PPI group (61.6% [49.4–74.3%], p < 0.01). Conclusions: Vonoprazan serves as a diagnostic tool to exclude acid-related GERD.

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