Pathogenesis of Potassium-Competitive Acid Blocker-Resistant Non-Erosive Reflux Disease

Abstract

Background: The present study examined the pathogenesis of potassium-competitive acid blocker (P-CAB)-resistant non-erosive reflux disease (NERD). Methods: Forty-three patients with NERD, who had persistent reflux symptoms despite the administration of P-CAB, were included in this study. After excluding eosinophilic esophagitis and primary esophageal motility disorders, esophageal impedance-pH monitoring was performed. In symptom index (SI)-positive patients, the mechanism of SI-positivity and percent time with intragastric pH > 4 and with esophageal pH < 4 were investigated according to the presence or absence of Helicobacter pylori infection. Results: One (2.3%) of 43 patients had a primary esophageal motility disorder (Jackhammer esophagus). Eighteen (41.9%) and 3 (7%) patients were SI-positive for liquid and gas-only reflux, respectively, and the remaining 21 patients who were SI-negative (48.8%) had functional heartburn. All patients SI-positive for liquid reflux were SI-positive for weakly acidic reflux. Gastric acid was sufficiently suppressed by P-CAB, regardless of the presence or absence of H. pylori infection. Conclusions: The pathogenesis of ­P-CAB-resistant NERD was elucidated in 51% of patients. Symptoms in all patients SI-positive for liquid reflux were related to weakly acidic reflux, and symptoms related to acid reflux may be ruled out by the administration of P-CAB.

Efficacy of <i>Rikkunshito</i> for Functional Heartburn: A Prospective Pilot Study

“…Regarding correlation between changes in FSSG score from 8 weeks after treatment or discontinuation to before treatment and OTE, correlations were found between total FSSG score and OTE, and between FSSG RS score and OTE (total FSSG vs. OTE: r = 0.857, P = 0.0017; FSSG RS vs. OTE: r = 0.857, P = 0.0017) ( Figure 7). Contrarily, in a previous study, no patients had symptoms caused by acid reflux on administration of P-CAB 6 . Therefore, patients with functional heartburn can be more readily selected from those with P-CAB-resistant NERD.…”

“…Functional heartburn is a cause of proton pump inhibitor (PPI)resistant NERD, and it was reported that around 20%-50% of patients with PPIresistant NERD have functional heartburn [2][3][4][5] . Additionally, approximately half of NERD patients who are resistant to potassium-competitive acid blocker (P-CAB) (novel and potent acid secretion inhibitor), and whose symptoms do not improve, have functional heartburn [6][7][8] . Although the pathophysiology of functional heartburn is unclear, the appearance symptoms is not triggered by reflux.…”

Clinical Characterization of Vonoprazan-Refractory Gastroesophageal Reflux Disease

“…The newly developed potassium-competitive acid blocker vonoprazan has a much greater ability to suppress gastric acid production than conventional PPIs [16,17], and as expected, vonoprazan has shown strong efficacy for treating GERD in clinical practice in Japan. In the present study, we examined whether or not there was any marked difference in the proportion of underlying disease conditions between conventional PPI-and vonoprazan-resistant GERD in clinical practice by performing both HRM and MII-pH monitoring [11,18]. We subsequently observed a significant difference in the proportion of underlying disease conditions between these 2 types of resistant GERD.…”

“…Vonoprazan has the potential to normalize the oesophageal acid exposure time (AET) in GERD patients and cure acid-related EE and NERD [9,10]. It was recently reported that symptoms related to acid reflux might be ruled out by vonoprazan [11], but further evidence is yet needed before it can be applied to clinical practice.…”

Convenient Method of Measuring Baseline Impedance for Distinguishing Patients with Functional Heartburn from those with Proton Pump Inhibitor-Resistant Endoscopic Negative Reflux Disease

“…Previous studies reported that switching to P-CAB from conventional PPIs achieved high mucosal healing rates in patients with PPI-refractory reflux esophagitis [6,7]. However, even with the use of P-CAB, NERD patients refractory to P-CAB therapy still exist and the pathogenesis of these patients was complex [8]. These data mean that acid reflux has only a minor effect on the pathophysiologic mechanism of NERD.…”