Efficacy and Safety of Potassium-competitive Acid Blockers Versus Proton Pump Inhibitors in Treating Erosive Esophagitis: A Meta-analysis Based on Randomized Controlled Trials.

OBJECTIVE: This meta-analysis aimed to investigate the efficacy and safety of potassium-competitive acid blockers (P-CABs) and proton pump inhibitors (PPIs) in treating erosive esophagitis (EE). METHODS: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched using predefined search terms up to January 2024. Relevant randomized controlled trials were included. The outcoming were the EE healing rate and treatment-related adverse events incidence. RESULTS: Nine randomized controlled trials involving 4012 patients were included. Patients receiving P-CAB exhibited a significantly better overall healing rate compared with PPI at week 2 [risk ratio (RR) = 1.06], but no statistical difference was observed at week 4 and week 8. Subgroup analysis revealed that P-CAB demonstrated a higher healing rate for patients with Los Angeles (LA) grade C/D, regardless of the assessment at week 2 (RR = 1.17), week 4 (RR = 1.10), or week 8 (RR = 1.08). However, no significant difference was found between PPI and P-CAB for patients with LA grade A/B at week 2, week 4, or week 8. Furthermore, patients treated with P-CAB had lower recurrence rates during maintenance therapy compared with PPI (RR = 0.79). In terms of safety, P-CAB was associated with a lower incidence of headache compared with PPI (RR = 0.32), with no statistical difference found in any treatment-related adverse events between the two groups. CONCLUSIONS: P-CAB was found to be safe and effective for EE treatment compared with PPI, particularly in 2-week short-term treatment, severe EE (LA grade C/D) treatment, or maintenance therapy. Limitations such as potential heterogeneity among included trials should be considered in the interpretation of these findings.

In grade C/D erosive esophagitis, vonoprazan ranks highest among PPIs and P-CABs for healing and maintaining remission.

SOURCE CITATION: Zhuang Q, Chen S, Zhou X, et al. Comparative efficacy of P-CAB vs proton pump inhibitors for grade C/D esophagitis: a systematic review and network meta-analysis. Am J Gastroenterol. 2024;119:803-813. 38345252.

Columbianadin ameliorates experimental acute reflux esophagitis in rats via suppression of NF-κB pathway.

PURPOSE: Reflux esophagitis is a condition characterized by inflammation and irritation of the esophagus, resulting from the backflow of stomach acid and other gastric contents into the esophagus. Columbianadin is a coumarin derivative that exhibits anti-inflammatory and antioxidant effects. In this study, we tried to scrutinize the protective effect of Columbianadin against acute reflux esophagitis in rats. METHODS: RAW 264.7 cells were utilized to assess cell viability and measure the production of inflammatory parameters. The rats received anesthesia, and reflux esophagitis was induced via ligation of pylorus and fore stomach and corpus junction. Rats received the oral administration of Columbianadin (25, 50 and 100 mg/kg) and omeprazole (20 mg/kg). The gastric secretion volume, acidity, and pH were measured. Additionally, the levels of oxidative stress parameters, cytokines, and inflammatory markers were determined. At the end of the study, mRNA expression was assessed. RESULTS: Columbianadin remarkably suppressed the cell viability and production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and prostaglandin (PGE2). Columbianadin treatment remarkably suppressed the secretion of gastric volume, total acidity and enhanced the pH level in the stomach. Columbianadin remarkably altered the level of hydrogen peroxidase, free iron, calcium, and plasma scavenging activity, sulfhydryl group; oxidative stress parameters like malonaldehyde, glutathione, superoxide dismutase, catalase, glutathione peroxidase; inflammatory cytokines viz., TNF-α, IL-6, IL-1ß, IL-10, IL-17, and monocyte chemoattractant protein-1; inflammatory parameters including PGE2, iNOS, COX-2, and nuclear kappa B factor (NF-κB). Columbianadin remarkably (P < 0.001) suppressed the mRNA expression TNF-α, IL-6, IL-1ß and plasminogen activator inhibitor-1. CONCLUSIONS: Columbianadin demonstrated a protective effect against acute reflux esophagitis via NF-κB pathway.

Long-term endoscopic change of gastric polyp associated with administration of vonoprazan.

Vonoprazan (VPZ) has been available in Japan since 2015. Endoscopic features of proton-pump inhibitor (PPI)-related gastric mucosal changes, including fundic gland and hyperplastic polyps, have been observed. However, the relationship between gastric polyps and VPZ remains unclear. A 65-year-old man with reflux esophagitis-associated symptoms refractory to PPI was referred to our hospital. VPZ (20 mg) was administered for 3 weeks, which proved effective. Afterward, VPZ dose was reduced to 10 mg; the reflux symptoms worsened, and 20 mg VPZ was restarted. Afterward, esophagogastroduodenoscopy (EGD) revealed a gradually enlarging gastric polyp in the cardia. After 5 years of VPZ administration, the patient developed a reddish polyp (approximately 10 mm) with a whitish substance in the cardia. Based on the clinical course, the polyp was considered to have enlarged because of the long-term VPZ administration. After being informed of the endoscopic findings, the patient decided to discontinue VPZ. One year after VPZ discontinuation, EGD revealed a shrunken polyp (5 mm). Long-term acid suppression causes hypergastrinemia, which may lead to gastric mucosal changes, including gastric polyps. There are few case reports of a decrease in the number and size of gastric polyps after VPZ discontinuation. Hence, some VPZ-induced endoscopic changes may be reversible.

Vonoprazan 10 mg or 20 mg vs. lansoprazole 15 mg as maintenance therapy in Asian patients with healed erosive esophagitis: A randomized controlled trial.

BACKGROUND: Erosive esophagitis (EE) is a gastroesophageal reflux disease characterized by mucosal breaks in the esophagus. Proton pump inhibitors are widely used as maintenance therapy for EE, but many patients still relapse. In this trial, we evaluated the noninferiority of vonoprazan vs. lansoprazole as maintenance therapy in patients with healed EE. METHODS: We performed a double-blind, double-dummy, multicenter, phase 3 clinical trial among non-Japanese Asian adults with endoscopically confirmed healed EE from April 2015 to February 2019. Patients from China, South Korea, and Malaysia were randomized to vonoprazan 10 mg or 20 mg once daily or lansoprazole 15 mg once daily for 24 weeks. The primary endpoint was endoscopically confirmed EE recurrence rate over 24 weeks with a noninferiority margin of 10% using a two-sided 95% confidence interval (CI). Treatment-emergent adverse events (TEAEs) were recorded. RESULTS: Among 703 patients, EE recurrence was observed in 24/181 (13.3%) and 21/171 (12.3%) patients receiving vonoprazan 10 mg or 20 mg, respectively, and 47/184 (25.5%) patients receiving lansoprazole (differences: -12.3% [95% CI, -20.3% to -4.3%] and -13.3% [95% CI, -21.3% to -5.3%], respectively), meeting the primary endpoint of noninferiority to lansoprazole in preventing EE recurrence at 24 weeks. Evidence of superiority (upper bound of 95% CI <0%) was also observed. At 12 weeks, endoscopically confirmed EE recurrence was observed in 5/18, 2/20, and 7/20 of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. TEAEs were experienced by 66.8% (157/235), 69.0% (156/226), and 65.3% (158/242) of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. The most common TEAE was upper respiratory tract infection in 12.8% (30/235) and 12.8% (29/226) patients in vonoprazan 10 mg and 20 mg groups, respectively and 8.7% (21/242) patients in lansoprazole group. CONCLUSION: Vonoprazan maintenance therapy was well-tolerated and noninferior to lansoprazole for preventing EE recurrence in Asian patients with healed EE. TRIAL REGISTRATION: https://clinicaltrials.gov; NCT02388737.

Comparative Efficacy of P-CAB vs Proton Pump Inhibitors for Grade C/D Esophagitis: A Systematic Review and Network Meta-analysis.

INTRODUCTION: Los Angeles grade C/D esophagitis is a severe manifestation of gastroesophageal reflux disease that require active treatment and close follow-up. Potassium competitive acid blockers (P-CAB) are promising alternatives to proton pump inhibitors (PPI). We aimed to compare the efficacy and safety of P-CAB and PPI in healing grade C/D esophagitis to aid clinical decision-making. METHODS: A systematic literature search was performed using PubMed, MEDLINE, and Cochrane Central Register of Controlled Trials. Randomized controlled trials were eligible for inclusion if efficacy of P-CAB and PPI in healing grade C/D esophagitis was reported. Pooled risk ratios and risk difference with 95% credible intervals were used to summarize estimated effect of each comparison. The benefit of treatments was ranked using the surface under the cumulative probability ranking score. RESULTS: Of 5,876 articles identified in the database, 24 studies were eligible. Studies included incorporated 3 P-CAB (vonoprazan, tegoprazan, and keverprazan) and 6 PPI (lansoprazole, esomeprazole, omeprazole, rabeprazole extended-release (ER), pantoprazole, and dexlansoprazole). Based on the failure to achieve mucosal healing, 20 mg of vonoprazan q.d. ranked the first among PPI in initial and maintained healing of grade C/D esophagitis (surface under the cumulative probability ranking score = 0.89 and 0.87, respectively). Vonoprazan had similar risk of incurring adverse events, severe adverse events, and withdrawal to drug when compared with PPI. For those who attempted lower maintenance treatment dose, 10 mg of vonoprazan q.d. was a reasonable choice, considering its moderate efficacy and safety. DISCUSSION: Vonoprazan has considerable efficacy in initial and maintained healing of grade C/D esophagitis compared with PPI, with moderate short-term and long-term safety.

Vonoprazan is superior to lansoprazole for healing of severe but not mild erosive esophagitis: A systematic review with meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Healing rates of severe erosive esophagitis (EE; Los Angeles [LA] Grade C/D) in patients treated with a proton pump inhibitor (PPI) is suboptimal (~60-70%). Vonoprazan, a potassium-competitive acid blocker, is suggested to have better healing rates in patients with severe EE. This meta-analysis compares the efficacy and safety of vonoprazan 20 mg versus lansoprazole 30 mg daily in healing EE, specifically in those with LA Grade C/D. METHODS: We searched MEDLINE, Embase, and CENTRAL on May 24, 2023. Studies that randomized EE patients to vonoprazan 20 mg daily or lansoprazole 30 mg daily and compared healing rates were included. The risk of bias was assessed using Cochrane's Risk of Bias 2 tool. The fixed-effect model was used to obtain the pooled efficacy and safety outcomes. Subgroup analysis was done to compare healing rates in mild (LA Grade A/B) versus severe EE and based on study location. RESULTS: Four randomized controlled trials (RCTs) with low risks of bias comprising 2208 participants were included. Vonoprazan 20 mg was superior to lansoprazole 30 mg daily in healing severe EE at all weeks (Week 2 RR 1.294 [95% CI 1.169-1.433], Week 4 1.160 [1.059-1.270], and Week 8 1.175 [95% CI 1.107-1.247]), but was similar for mild EE at all weeks (P-interaction < 0.01). Vonoprazan 20 mg was more efficacious than lansoprazole 30 mg at Week 8 in Western versus Asian studies (P-interaction < 0.01). Any, serious, and drug-related treatment-emergent adverse events were comparable between groups. CONCLUSION: Vonoprazan 20 mg is superior to lansoprazole 30 mg for healing severe EE but not mild EE. Vonoprazan 20 mg daily has a similar safety profile to lansoprazole 30 mg daily.

Xuanfu Daizhe Tang alleviates reflux esophagitis in rats by inhibiting the STAT1/TREM-1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Reflux esophagitis (RE) is a common chronic inflammatory disease of the esophageal mucosa with a high prevalence and recurrence rate, for which a satisfactory therapeutic strategy is still lacking. Chinese medicine has its characteristics and advantages in treating RE, and the clinical application of Xuanfu Daizhe Tang (XDT) in treating RE has achieved sound therapeutic effects. However, there needs to be more research on its mechanism of action. AIM OF THE STUDY: The present work aimed to investigate the mechanism of XDT action in RE through the Signal Transducer and Activator of Transcription 1 (STAT1)/Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) pathway. MATERIALS AND METHODS: The main active components of XDT were analyzed by ultra-performance liquid chromatography-mass spectrometer (UPLC-MS). The effect of XDT on RE was evaluated in a rat model of RE induced by "Cardioplasty + pyloric ligation + Roux-en-Y esophagojejunostomy". Each administration group was treated by gavage. The degree of damage to the esophageal mucosa was evaluated by visual observation, and the Potential of Hydrogen (PH) method and Hematoxylin-eosin staining (HE) staining were performed. Serum levels of Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), Tumor Necrosis Factor alpha (TNF-α), and Inducible Nitric Oxide Synthase (iNOS) were measured by ELISA. Quantitative Real-time PCR (qPCR), Western Blot (WB), and Immunofluorescence (IF) methods were used to detect Claudin-4, Claudin-5, TREM-1, and p-STAT1 in esophageal tissues for studying the mechanism of action and signaling pathway of XDT. Immunohistochemistry (IHC) analysis was used to detect the expression of TREM-1 and CD68 in esophageal tissues. Flow Cytometry (FC) was used to detect the polarization of macrophages in the blood. After conducting preliminary experiments to verify our hypothesis, we performed molecular docking between the active component of XDT and STAT1 derived from rats and parallel experiments with STAT1 inhibitor. The selective increaser of STAT1 transcription (2-NP) group was used to validate the mechanism by which XDT acts. RESULTS: XDT alleviated esophageal injury and attenuated histopathological changes in RE rats. XDT also inhibited the inflammatory response and decreased serum IL-1ß, IL-6, TNF-α, and iNOS levels in RE rats. qPCR and WB results revealed that XDT inhibited the expression of Claudin-4, Claudin-5, TREM-1, and STAT1 in the esophageal mucosa of RE rats. IHC and FC results showed that XDT reduced TREM-1 levels in esophageal tissues and polarized macrophages toward M2. The molecular docking results showed that rat-derived STAT1 can strongly bind to Isochronogenic acid A in XDT. The parallel experimental results of STAT1 inhibitor showed that XDT has anti-inflammatory effects similar to STAT1 inhibitors. The 2-NP group confirmed that XDT exerts its therapeutic effect on reflux esophagitis through the STAT1/TREM-1 pathway, with STAT1 as the upstream protein. CONCLUSIONS: This study suggests that XDT may treat reflux esophagitis by modulating the STAT1/TREM-1 pathway.

Prevalence and risk factors for medication-refractory reflux esophagitis in patients with systemic sclerosis in Japan.

BACKGROUNDS: Patients with systemic sclerosis (SSc) often have esophageal motility abnormalities and weak esophago-gastric junction (EGJ) barrier function, which causes proton pump inhibitor (PPI)-refractory reflux esophagitis (RE). The aims of this study were to clarify the current management of RE and prevalence and risk factors of medication-refractory RE in patients with SSc in Japan. METHODS: A total of 188 consecutive patients with SSc who underwent both esophageal high-resolution manometry (HRM) and esophagogastroduodenoscopy (EGD) were reviewed. The presence of RE and grades of the gastroesophageal flap valve (GEFV) were assessed. Esophageal motility was assessed retrospectively according to the Chicago classification v3.0. When RE was seen on a standard dose of PPI or any dose of vonoprazan (VPZ), it was defined as medication-refractory RE. RESULTS: Approximately 80% of patients received maintenance therapy with acid secretion inhibitors regardless of esophageal motility abnormalities. Approximately 50% of patients received maintenance therapy with PPI, and approximately 30% of patients received VPZ. Medication-refractory RE was observed in 30 patients (16.0%). In multivariable analyses, the number of EGD and absent contractility were significant risk factors for medication-refractory RE. Furthermore, combined absent contractility and GEFV grade III or IV had higher odds ratios than did absent contractility alone. CONCLUSIONS: Patients with persistent reflux symptoms and those with absent contractility and GEFV grade III or IV should receive maintenance therapy with strong acid inhibition to prevent medication-refractory RE.

The efficacy and safety of fexuprazan in treating erosive esophagitis: a phase III, randomized, double-blind, multicenter study.

BACKGROUND AND AIM: Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE). METHODS: This was a phase III, randomized, double-blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4-8 weeks. The healing rates of EE, symptom response, GERD-health-related quality life (GERD-HRQL), and treatment-emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group. RESULTS: A total of 332 subjects were included in full analysis set (FAS) and 311 in per-protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD-HRQL. The incidence of drug-related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm. CONCLUSION: This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561.

Efficacy and safety of HIP1601 (dual delayed-release esomeprazole) 40 mg in erosive esophagitis compared to HGP1705 (delayed-release esomeprazole) 40 mg: a multicenter, randomized, double-blind, non-inferiority study.

BACKGROUND: Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE). METHODS: We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups. RESULTS: By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups. CONCLUSIONS: The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD. TRIAL REGISTRATION: NCT04080726 ( https://classic. CLINICALTRIALS: gov/ct2/show/NCT04080726 ), registration date: 25/10/2018.

Network meta-analysis of multiple doses of vonoprazan for the treatment of erosive esophagitis.

Aim: 20 mg of vonoprazan (VPZ20) is recommended in most countries to treat erosive esophagitis (EE). Whether other doses of vonoprazan, such as 5 mg (VPZ5), 10 mg (VPZ10), 20 mg (VPZ20), and 40 mg (VPZ40) are more effective is unknown. Materials & methods: Three databases were electronically searched to identify studies published before November 2021. Network meta-analysis was performed using STATA 14.0. Results: VPZ20 and VPZ40 were comparable to PPI, VPZ5 and VPZ10 in 4- and 8-week healing rates, and this was also detected in patients with refractory EE. All regimens resulted in similar treatment-emergent adverse events (TEAEs). However, VPZ40 ranked first for healing rate and TEAEs; however, VPZ20 ranked worst for TEAEs. Conclusion: Different doses of VPZ are comparable in efficacy and safety, but VPZ40 may be best in both effectiveness and safety.

Therapeutic Effect of Polaprezinc on Reflux Esophagitis in the Rat Model.

BACKGROUND/AIMS: To explore the protective effects and therapeutic mechanism of Esomeprazole (PPI), polaprezinc granule (PZ), and PPI + PZ on reflux esophagitis (RE) in the rat model. METHODS: Wistar rats were randomly divided into 9 groups, which contain the control group, the acid cessation group (0.7% HCl, Q3D × 4), and the acid persistence group (0.7% HCl, Q3D × 11). PPI was administered by gavage at 8 mg·kg-1 body weight and PZ was administered by gavage at 120 mg·kg-1 body weight once a day for 15 days. The gastric cardia tissue of the feeding tube was observed under the light microscope, and the levels of interleukin-8 (IL-8) and prostaglandin E2 (PGE2) were measured by ELISA. The expression of EGFR, Akt, p-Akt, and p-mTOR was detected by Western blot. RESULTS: The ELISA results showed that the levels of IL-8 and PGE2 were significantly increased in the model group, but decreased in all groups after treatment. In the acid cessation group, PZ treatment had the most significant effect on reducing IL-8 levels and PPI + PZ treatment had the most significant effect on reducing PGE2 levels. In the acid persistence group, the PPI treatment had the most significant effect on reducing the levels of IL-8 and PGE2, and the PZ treatment could also significantly reduce their levels, close to the normal value. Western blot results showed that the expression of PI3K/Akt/mTOR pathway protein was increased in the model group, while its expression was decreased after treatment. CONCLUSIONS: Polaprezinc has a significant therapeutic effect on RE in rats, which can reduce the levels of IL-8 and PGE2 and downregulate the expression of PI3K/Akt/mTOR signal pathway protein. The efficacy of polaprezinc in the treatment of reflux esophagitis is comparable to that of PPI, and the combination of them is more effective in the reflux esophagitis treatment.

Microbiota in Reflux Esophagitis and Peptic Ulcer Disease.

Gastroesophageal reflux disease (GERD), reflux esophagitis (RE), and peptic ulcer disease (PUD) are commonly encountered in clinical practice. More than simple anatomic abnormalities, these conditions are tethered to a variety of external influences as well as those related to genomics, transcriptomics, and metabolomics. Furthermore, each of these conditions is clearly related to abnormalities of the microbiota of the oropharynx, esophagus, and gastrointestinal tract. Certain therapeutics used to address these conditions such as antibiotic agents and proton pump inhibitors worsen microbiome dysbiosis while pursuing clinical benefit. Therapeutics that protect, shape adaptively, or restore microbiota balance are key aspects of current and future therapy to pursue. How the microbiota is involved in clinical condition genesis and progression, as well as how therapeutic support or derange the microbiota are herein explored.

Long-Term Clinical Course after Successful Initial Treatment in Patients with Mild Erosive Esophagitis: A Prospective Follow-Up Study.

INTRODUCTION: This study aimed to investigate the clinical course of patients with healed mild erosive esophagitis and clarify the predictive factors for continuous treatment. METHOD: Fifty-one patients with mild erosive esophagitis who confirmed mucosal healing by endoscopy after initial treatment with vonoprazan (VPZ) were enrolled. The patients continued subsequent treatment of their choice: maintenance therapy with VPZ 10 mg (n = 15), on-demand therapy with VPZ 20 mg (n = 19), or no medication (n = 17). Each patient was prospectively followed up for over 2 years, and the treatment was switched to other options appropriately according to their symptoms. RESULTS: During the mean follow-up period of 3.1 years (range: 2.0-3.9 years), 2 patients who chose maintenance therapy switched to on-demand therapy. One patient who chose on-demand therapy switched to maintenance therapy, while 3 patients switched to no medication. Recurrence of symptoms occurred in 9 patients who chose no medication. They were administered maintenance therapy and five of them were subsequently switched to on-demand therapy. Ultimately, the proportion of patients receiving each treatment was 35.3% (18/51) for maintenance therapy, 43.1% (22/51) for on-demand therapy, and 21.6% (11/51) for no medication. A predictive factor for the need for continuous treatment was the presence of esophageal hiatal hernia (odds ratio: 6.03, 95% confidence interval: 1.43-25.3, p = 0.014). CONCLUSION: Among patients with healed mild erosive esophagitis, 78.4% required continuous treatment with VPZ, while 21.6% remained symptom free with no medication. On-demand therapy was the most common treatment, and continuous treatment may be recommended for patients with esophageal hiatal hernia.

Elevated Pro-inflammatory Cytokine Levels in Acute Reflux Esophagitis Are Reduced by 1,25 Dihydroxy Vitamin D3.

BACKGROUND/AIM: Gastric acid reflux into the esophagus can cause irritation and inflammation of the esophagus and progress to reflux esophagitis (RE). Vitamin D3 (VitD3) has anti-inflammatory effects and plays an important regulatory role in adaptive and innate immunity. We hypothesized that VitD3 may play a protective role in RE. MATERIALS AND METHODS: Seventy male Sprague-Dawley rats were used, and acute RE (n=35) or chronic RE (n=35) were surgically induced. The effects of different doses of VitD3 on morphological changes and alteration of pro-inflammatory cytokine levels were examined in the rat models. Western blot analysis was performed to determine protein expression levels of IL-1ß, IL-6, and IL-8 in esophageal tissues. Serum levels of VitD3 and calcium were determined using enzyme-linked immunosorbent assays. RESULTS: The protein expression of pro-inflammatory cytokines IL-1ß, IL-6, and IL-8 was found significantly increased in RE. VitD3 treatment significantly reduced the levels of these pro-inflammatory cytokines in both the low-dose and high-dose VitD3 groups compared to control groups in acute RE, but not chronic RE. Macrographic and histopathological examination revealed various degrees of esophageal impairment in rats following surgical induction of acute or chronic RE in rats. These impairments were not improved by VitD3. Morphological grading of esophageal mucosa showed no significant differences between acute and chronic RE. Elevated serum levels of calcium were observed after VitD3 treatment. CONCLUSION: IL-1ß, IL-6, and IL-8 levels were significantly elevated in RE. The abnormal increase in these important pro-inflammatory cytokines was suppressed by VitD3 in the rat models of acute RE. These novel findings suggest a potential protective role of VitD3 in early-stage RE.

Proton Pump Inhibitor Treatment Has Little Effects on Secretion of Saliva in Patients with Proton Pump Inhibitor-Responsive Mild Reflux Esophagitis and Non-Erosive Reflux Disease.

INTRODUCTION: The secretion of saliva, which is triggered by acid reflux into the esophagus via the esophagosalivary reflex, plays a crucial role in the defensive mechanisms of the esophagus. The volume of saliva secreted in patients with gastroesophageal reflux disease (GERD) is reduced. However, the effects of proton pump inhibitors (PPI) on the secretion of saliva have rarely been reported. Therefore, the present study investigated changes in the volume and pH of saliva after the cessation of PPI. MATERIALS AND METHODS: We retrospectively reviewed the records of consecutive patients previously diagnosed with mild reflux esophagitis (RE) or non-erosive reflux disease (NERD) controlled with PPI (including vonoprazan) who performed the salivary secretion test before and after a 2-week cessation of PPI. The volume, pH, and pH after acid loading (buffering capacity) of saliva were compared before and after the cessation of PPI. RESULTS: Thirty-two patients (25 NERD, 7 mild RE) were included. The second saliva test was performed a median interval of 14 months [12.0-15.3] after the first test. No significant differences were observed in the volume of saliva secreted before and after the cessation of PPI (before 4.0 mL [2.7-6.0] vs. after 4.0 mL [2.3-5.9], p = 0.894). No significant differences were noted in pH or changes in pH after acid loading before and after the cessation of PPI (pH: before 7.1 ± 0.24 vs. after 7.0 ± 0.24, p = 0.1. Delta pH after acid loading: before 1.0 [0.8-1.2] vs. after 1.0 [0.8-1.2], p = 0.844). CONCLUSION: The cessation of PPI did not appear to affect the volume, pH, or buffering capacity of saliva in patients with PPI-responsive mild RE and NERD.