Clinical features of gastroesophageal reflux disease and erosive esophagitis:Insights from patients undergoing esophagogastroduodenoscopy in resource-limited Ethiopia

BACKGROUND Gastroesophageal reflux disease(GERD)is a common disease worldwide with varying clinical presentations and risk factors.Prevalence data for Africa is lacking,but an increasing trend is expected due to demographic and epidemiological transitions.Although endoscopic studies for general gastrointestinal disorders have shown some patients with erosive esophagitis(EE),no studies in Ethiopia have investigated the clinical characteristics,risk factors,and severity of GERD using esophagogastroduodenoscopy(EGD).AIM To assess the clinical features of GERD in Ethiopian patients who underwent EGD and determine the severity and risk factors of EE.METHODS We conducted a multicenter,retrospective cross-sectional study of 221 patients diagnosed with GERD and endoscopic findings of EE at Trauma Associated Severe Hemorrhage and Amniotic Membrane Stem Cell between January 2019 and August 2022.Data were collected from electronic medical records and phone call interviews.We used descriptive statistics and binary logistic regression analysis with SPSS version 26 to identify the association between variables with a statistical significance set at P value<0.05.RESULTS The mean±SD age of the patients was 44.8(±15.9)years,with a male-to-female ratio of 1.6:1.The most commonly reported symptom was epigastric pain(80.5%),followed by heartburn(43%).Los Angeles(LA)-A EE was diagnosed in 71.1%of patients,followed by LA-B(14.9%),LA-C(7.7%),and LA-D(5.9%).Multivariate analysis showed that age 50 or above,presence of bleeding,and endoscopic findings of duodenitis/duodenopathy were significantly associated with severe EE(P<0.05).Stricture and Barrett’s esophagus were observed in 4.5%and 1.36%of patients with EE,respectively.CONCLUSION Most of the patients had milder EE with fewer complications.However,severe EE was more prevalent in older patients and those with duodenitis/duodenopathy.

Metabolic syndrome is associated with erosive esophagitis

AIM： To clarify whether insulin resistance and metabolic syndrome are risk factors for erosive esophagitis.METHODS： A case-control study was performed using the database of the Kangbuk Samsung Hospital Medical Screening Center.RESULTS： A total of 1679 cases of erosive esophagitis and 3358 randomly selected controls were included. Metabolic syndrome was diagnosed in 21% of the cases and 12% of the controls （P 〈 0.001）. Multiple logistic regressions confirmed the association between erosive esophagitis and metabolic syndrome （Odds ratio, 1.25; 95% CI, 1.04-1.49）. Among the components of metabolic syndrome, increased waist circumference, elevated serum triglyceride levels and hypertension were significant risk factors for erosive esophagitis （all P 〈 0.01）. Furthermore, increased insulin resistance （Odds ratio, 0.91; 95% CI, 0.85-0.98） and fatty liver, as diagnosed by ultrasonography （odds ratio, 1.39; 95% CI, 1.20-1.60）, were also related to erosive esophagitis even afl：er adjustment for a series of confounding factors.CONCLUSION： Metabolic syndrome and increased insulin resistance are associated with an increased risk of developing erosive esophagitis.

Factors associated with complicated erosive esophagitis: A Japanese multicenter, prospective, cross-sectional study

AIMTo assess the clinical characteristics of patients with complicated erosive esophagitis (EE) and their associated factors.METHODSThis prospective, cross-sectional study included patients diagnosed with EE by upper gastrointestinal endoscopy between October 2014 and March 2015 at 106 Japanese hospitals. Data on medical history, general condition, gastrointestinal symptoms, lifestyle habits, comorbidities, and endoscopic findings were collected using a standard form to create a dedicated database. Logistic regression analysis was used to calculate adjusted odds ratios (aOR) and 95%CI for the association with complicated EE.RESULTSDuring the study period, 1749 patients diagnosed with EE, 38.3% of whom were prescribed proton pump inhibitors (PPIs) were included. Of them, 143 (8.2%) had EE complications. Esophageal bleeding occurred in 84 (4.8%) patients, esophageal strictures in 45 (2.6%) patients, and 14 (0.8%) patients experienced both. Multivariate analysis showed that increased age (aOR: 1.05; 95%CI: 1.03-1.08), concomitant use of psychotropic agents (aOR: 6.51; 95%CI: 3.01-13.61), and Los Angeles grades B (aOR: 2.69; 95%CI: 1.48-4.96), C (aOR: 15.38; 95%CI: 8.62-28.37), and D (aOR: 71.49; 95%CI: 37.47-142.01) were significantly associated with complications, whereas alcohol consumption 2-4 d/wk was negatively associated (aOR: 0.23; 95%CI: 0.06-0.61). Analyzing associated factors with each EE complication separately showed esophageal ulcer bleeding were associated with increased age (aOR: 1.05; 95%CI: 1.02-1.07) and Los Angeles grades B (aOR: 3.60; 95%CI: 1.52-8.50), C (aOR: 27.61; 95%CI: 12.34-61.80), and D (aOR: 119.09; 95%CI: 51.15-277.29), while esophageal strictures were associated with increased age (aOR: 1.07; 95%CI: 1.04-1.10), gastroesophageal reflux symptom (aOR: 2.51; 95%CI: 1.39-4.51), concomitant use of psychotropic agents (aOR: 11.79; 95%CI: 5.06-27.48), Los Angeles grades C (aOR: 7.35; 95%CI: 3.32-16.25), and D (aOR: 20.34; 95%CI: 8.36-49.53) and long-segment Barrett&#x02019;s esophagus (aOR: 4.63; 95%CI: 1.64-13.05).CONCLUSIONAging and severe EE were common associated factors, although there were more associated factors in esophageal strictures than esophageal ulcer bleeding. Despite the availability and widespread use of PPIs, EE complications are likely to remain a problem in Japan owing to the aging population and high-stress society.

Prevalence of Barrett's esophagus in patients with moderate to severe erosive esophagitis

AIM: To investigate the proportion of patients with moderate-severe erosive esophagitis (EE) who will have Barrett's esophagus (BE) after healing of inflammation. METHODS: Patients with EE of Los Angeles (LA) class B, C and D who underwent follow-up endoscopy documenting complete mucosal healing. RESULTS: A total of 86/169 patients were suspected of having BE (38 before healing and 48 after healing of EE) and, 46/86 eventually had the histological confirmation. At index esophago-gastro-duodenoscopy (EGD), BE was suspected in 38/169 (22%), and ultimately, histologically confirmed in 20 of these. In 11 patients where biopsies were performed in the presence of inflammation, BE was detected in 2 and missed in 5 (including 2 dysplasias). In 131/169 patients (77.5%), BE was not suspected at index EGD. After healing of EE though, 48 patients had suspicion of BE who underwent biopsies, and in 26 of these histology was positive for BE. The length of inflammation had a linear correlation with the length of BE (P = 0.01). Out of multiple variables to predict BE, only the suspicion at index endoscopy was statistically significant (P = 0.01). CONCLUSION: BE was seen in 46/169 (27%) patients with EE of LA class B, C and D. The length of EE can predict the length of underlying BE segment.Even when suspected, BE and associated dysplasia can be missed in the presence of inflammation; therefore, repeat evaluation should be considered after complete healing of esophagitis.

Head-to-head comparison of H_2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: A meta-analysis

AIM: To systematically evaluate the efficacy of H2-receptor antagonists (H2RAs) and proton pump inhibitors in healing erosive esophagitis (EE).METHODS: A meta-analysis was performed. A literature search was conducted in PubMed, Medline, Embase, and Cochrane databases to include randomized controlled head-to-head comparative trials evaluating the efficacy of H2RAs or proton pump inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI) were calculated under a random-effects model.RESULTS: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs standard dose H2RAs,1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vsstandard dose H2RAs, 1.59 (95%CI, 1.44-1.75);standard dose other proton pump inhibitors vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced consistently greater healing rates than H2RAs of all doses across all grades of esophagitis, including patients refractory to H2RAs. Healing rates achieved with standard dose omeprazole were similar to those with other proton pump inhibitors in all grades of esophagitis.CONCLUSION: H2RAS are less effective for treating patients with erosive esophagitis, especially in those with severe forms of esophagitis. Standard dose proton pump inhibitors are significantly more effective than H2RAs in healing esophagitis of all grades. Proton pump inhibitors given at the recommended dose are equally effective for healing esophagitis.

Association between body mass index and erosive esophagitis:A meta-analysis

AIM:To conduct a meta-analysis to estimate the determinants of the association between erosive esophagitis (EE)and body mass index(BMI). METHODS:We identified the studies using PubMed. Studies were selected for analysis based on certain inclusion and exclusion criteria.Data were extracted from each study on the basis of predefined items.Metaanalyses were performed to verify the risk factors,such as obesity and gender. RESULTS:Twenty-one studies were included in this systematic review.These studies demonstrated an association between increasing BMI and the presence of EE[95%confidence interval(CI):1.35-1.88,overweight,odds ratio(OR)=1.60,P value homogeneity =0.003,95%CI:1.65-2.55,obese,OR=2.05,P< 0.01].The heterogeneity disappeared by stratifying for gender.No publication bias was observed in this metaanalysis by the Egger method. CONCLUSION:This analysis demonstrates a positive association between BMI and the presence of EE,especially in males.The risk seems to progressively increase with increasing weight.

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.

Alginate controls heartburn in patients with erosive and nonerosive reflux disease

AIM:To evaluate the effect of a novel alginate-based compound,Faringel,in modifying reflux characteristics and controlling symptoms.METHODS:In this prospective,open-label study,40 patients reporting heartburn and regurgitation with proven reflux disease(i.e.,positive impedance-pH test/evidence of erosive esophagitis at upper endoscopy) underwent 2 h impedance-pH testing after eating a refluxogenic meal.They were studied for 1 h under basal conditions and 1 h after taking 10 mL Faringel.In both sessions,measurements were obtained in right lateral and supine decubitus positions.Patients also completed a validated questionnaire consisting of a 2-item 5-point(0-4) Likert scale and a 10-cm visual analogue scale(VAS) in order to evaluate the efficacy of Faringel in symptom relief.Tolerability of the treatment was assessed using a 6-point Likert scale ranging from very good(1) to very poor(6).RESULTS:Faringel decreased significantly(P < 0.001),in both the right lateral and supine decubitus positions,esophageal acid exposure time [median 10(25th75th percentil 6-16) vs 5.8(4-10) and 16(11-19) vs 7.5(5-11),respectively] and acid refluxes [5(3-8) vs 1(1-1) and 6(4-8) vs 2(1-2),respectively],but increased significantly(P < 0.01) the number of nonacid reflux events compared with baseline [2(1-3)vs 3(2-5) and 3(2-4) vs 6(3-8),respectively].Percentage of proximal migration decreased in both decubitus positions(60% vs 32% and 64% vs 35%,respectively;P < 0.001).Faringel was significantly effective in controlling heartburn,based on both the Likert scale [3.1(range 1-4) vs 0.9(0-2);P < 0.001] and VAS score [7.1(3-9.8) vs 2(0.1-4.8);P < 0.001],but it had less success against regurgitation,based on both the Likert scale [2.6(1-4) vs 2.2(1-4);P = not significant(NS)] and VAS score [5.6(2-9.6) vs 3.9(1-8.8);P = NS].Overall,the tolerability of Faringel was very good 5(2-6),with only two patients reporting modest adverse events(i.e.,nausea and bloating).CONCLUSION:Our findings demonstrate that Faringel is well-tolerated and effective in reducing heartburn by modifying esophageal acid exposure time,number of acid refluxes and their proximal migration.

Heartburn and regurgitation have different impacts on life quality of patients with gastroesophageal reflux disease

AIM: To investigate the impact of heartburn and regurgitation on the quality of life among patients with gastroesophageal reflux disease (GERD).

Local inflammatory response to gastroesophageal reflux:Association of gene expression of inflammatory cytokines with esophageal multichannel intraluminal impedance-pH data

BACKGROUND Gene expression of inflammatory cytokines may take part in the pathophysiology of different forms of gastroesophageal reflux disease(GERD).AIM To explore gene expression of inflammatory cytokines in esophageal mucosa in patients with erosive esophagitis(EE)and non-erosive forms of GERD(NERD)and its association with data of esophageal multichannel intraluminal impedancepH(MII-pH)measurements.METHODS This was a single-center prospective study.Esophageal mucosa samples were taken from the lower part of the esophagus during endoscopy.Expression of interleukin(IL)-1β,IL-10,IL-18,tumor necrosis factorα(TNFA),toll-like receptor 4(TLR4),GATA binding protein 3(GATA3),differentiation cluster 68(CD68)andβ-2 microglobulin genes in esophageal mucosa was assessed with ImmunoQuantex assays.MII-pH measurements were performed on all the participants.Diagnosis of GERD was confirmed by the results of the MII-pH data.Based on the endoscopy,patients were allocated to the groups of EE and NERD.The control group consisted of non-symptomatic subjects with normal endoscopy and MII-pH results.We used nonparametric statistics to compare the differences between the groups.Association of expression of the mentioned genes with the results of the MII-pH data was assessed with Spearman’s rank method.RESULTS Data from 60 patients with GERD and 10 subjects of the control group were available for the analysis.Higher expression of IL-18(5.89±0.4 vs 5.28±1.1,P=0.04)and GATA3(2.92±0.86 vs 2.23±0.96,P=0.03)was found in the EE group compared to NERD.Expression of IL-1β,IL-18,TNFA,and TLR4 was lower(P<0.05)in the control group compared to EE and NERD.Esophageal acid exposure correlated with the expression of IL-1β(Spearman’s rank r=0.29),IL-18(r=0.31),TNFA(r=0.35),GATA3(r=0.34),TLR4(r=0.29),and CD68(r=0.37).Mean esophagealрНcorrelated inversely with the expression of IL-18,TNFA,GATA3,TLR4,and CD68.No association of gene expression with the number of gastroesophageal refluxes was found.CONCLUSION In patients with EE,local expression of IL-18 and GATA3 was higher compared to subjects with NERD.Esophageal acid exposure correlated directly with expression of IL-1β,IL-18,TNFA,TLR4,CD68,andβ-2 microglobulin genes.Inverse correlation was revealed between expression of IL-18,TNFA,GATA3,TLR4,and CD68 and mean esophageal pH.

Prolapse gastropathy syndrome may be a predictor of pathologic acid reflux

AIM： To assess the occurrence of gastric acid reflux into the esophagus in endoscopically confirmed prolapse gastropathy syndrome （PGS）. METHODS： Using ambulatory esophageal pH measurement （BRAVOTM wireless esophageal pH monitoring system）, twenty-six patients with PGS were compared with twenty-one patients with erosive esophagitis （EE） as controls. We assessed several reflux parameters, including the percentage of total time at pH 〈 4, and the DeMeester score. RESULTS： There were no statistical differences between the PGS group and the EE group as to mean age, sex ratio and pH recording time. The EE group showed more severe reflux than the PGS group, as evaluated in terms of the longest duration of reflux, the number of reflux episodes, the number of reflux episodes lasting 〉 5 min, the total time with pH 〈 4 during acid reflux episodes, and the DeMeester score, but none of these parameters showed statistically significant difference. Although 53.8% （14/26） of the PGS group and 76.2% （16/22） of the EE group demonstrated pathologic acid reflux （DeMeester score 〉 14.72）, there was no statistically significant difference between the two groups in the incidence of pathologic acid reflux （P = 0.11）. CONCLUSION： There was no statistically significant difference in pathologic acid reflux between the PGS and EE group. These data suggest that endoscopically diagnosed PGS might be a predictor of pathologic acid reflux.