Journal of Biomedical and Biological Sciences

 

Gastroesophageal Reflux Disease: Definition, Risk Factors, Pathophysiology, and Management

Gudisa Bereda1*ORCID ID 

1Department of Pharmacy, Negelle Health Science College, Guji, Ethiopia

*Corresponding Author: Bereda G, Department of Pharmacy, Negelle Health Science College, Guji, Ethiopia. E-mail: gudisabareda95@gmail.com

Citation: Bereda G. Gastroesophageal Reflux Disease: Definition, Risk Factors, Pathophysiology, and Management. Journal of Biomedical and Biological Sciences. 2022;1(2):1-10.

 

Copyright: © 2022 Bereda G. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received On: 9th January,2022     Accepted On: 1st February,2022    Published On: 10th February,2022

Abstract

Gastroesophageal reflux defined as the symptoms or mucosal damage resulting from the abnormal retrograde movement of gastric contents from the stomach back up to the esophagus. The greater the length of this section, the further valve-like an outcome there is 3rd, the angle between the stomach and the oesophagus (the angle of His) also supports to prevent reflux. Gastroesophageal reflux diseases are usually caused by a transient relaxation of the lower esophageal sphincter and less commonly by a transient escalate in intraabdominal pressure or a low resting pressure of the lower esophageal sphincter. Reduce weight (overweight); obesity increases upper abdominal pressure, thereby provoking an increase in gastroesophageal reflux. Proton pump inhibitors are so far the consummate powerful agents for the treatment of reflux esophagitis. These medications are effective in healing reflux esophagitis and relieving affiliated symptoms. Consummately available proton pump inhibitors drugs are: lansoprazole, omeprazole, pantoprazole, esomeprazole. The objective of this review will explain about gastroesophageal reflux disease overview including pathophysiology, risk factors and finally management of the disease.

Keywords: Definition; Gastroesophageal Reflux Disease; Management; Pathophysiology; Risk Factors 

Introduction

 The American College of Gastroenterology (ACG) guidelines defines GERD as “symptoms or complications sequencing that the reflux of gastric contents into the esophagus or beyond, into the oral cavity (involving larynx) or lung” [1, 2]. As esophagus is redundantly exposed to refluxed material for extended periods, inflammation of the esophagus can occur as reflux esophagitis and in some cases, it progresses to erosion of the squamous epithelium as erosive esophagitis. GERD can be categorized as NERD or ERD depend on the availability or absence of esophageal mucosal injury visible on endoscopy [3].

Anti-reflux mechanism of the LOS: Gastroesophageal reflux may also associate with defective LES pressure or function. The pressure on the LES acts as a stumbling block to acid reflux from the stomach. The sphincter is anatomically not having a simple valve at a single point, but a physiological sphincter scaling in length from three to seven centimeter. The length of the sphincter can be ascertained further accurately using oesophageal manometry [4]. The restrain of the LES is via the coordination of various closing and opening mechanisms. Several closing mechanisms supply towards the appropriate work of the LES. 1st, the crux of the diaphragm creates a pinch cork action and works to escalate the pressure. This action can simply observe during upper gastro-intestinal endoscopy [5]. 2nd, the intra-abdominal section of the oesophagus is a crucial aspect of the anti-reflux barrier. The greater the length of this section, the further valve-like an outcome there is [6].3rd, the angle between the stomach and the oesophagus (the angle of His) also supports to prevent reflux [7]. Conversely, powers that tend to escalate opening pressure mechanisms oppose the closing mechanisms. Escalated intra-abdominal pressure (example from abdominal tumours, coughing, and constipation) escalates intra-gastric pressure and thus potentiates the pitfall of GERD [8].

 

Stage

Savary and Miller

Los Angeles classification

Stage I/A

One or more longitudinal non-confluent mucosal lesions with erythema, often covered with exudate above or extending from the gastroesophageal junction

Mucosal breaks confined to the mucosal fold each no longer than 5 mm

Stage II/B

Confluent erosive and exudative mucosal lesions which do not cover the entire circumference of the esophagus

At least one mucosal break longer than 5 mm confined to the mucosal fold but not continuous between two folds

Stage III/C

Circumferential erosive and exudative mucosal lesions covering the whole esophageal mucous membrane

Mucosal breaks that are continuous between the tops of mucosal folds but not circumferential

Stage IV/D

Chronic mucosal lesions such as ulcerations with or without stricture formation

Extensive mucosal breaks engaging at least 75% of the esophageal circumference

 

Table 1: Classification of reflux esophagitis according to Savary and Miller (1978; I–IV) and direct comparison to the Los Angeles classification (A–D).

Pathophysiology of GERD

Pathogenesis and peril factors of GERD are once there is an unbalance between the openings and closing pressures, gastroesophageal reflux disorder will happen. Factors that have been confirmed to change the pressure equilibrium and influence to gastroesophageal reflux disorder are: (1) meager work of LOS which is most probably to be seen in children who suffer from neuronal/muscular dysfunction; (2) oesophageal dysmotility sequencing in minimized clearance owing to medications (eg antihistamines) and hormones, as well as the neuronal disability can weaken oesophageal motility. Wenzl et al narrated that the incidence rate of gastroesophageal reflux disorder was consociated with the duration of gastric content staying in oesophagus and not the frequency of reflux; (3) abnormal anatomy involving congenital abnormalities (example short intra-abdominal oesophagus) or acquired diseases (example oesophageal atresia repair); and (4) higher intra-gastric pressure and delayed gastric emptying [9, 10]. Salivary flow is highly minimized during sleep, but saliva secreted intermittently in response to orofacial movements, such as chewing-like jaw activity or rhythmic masticatory muscle activity, assists to lubricate the esophageal mucosa [11].

Figure 1: the muscle layers at the gastroesophageal junction. The intrinsic muscle of the esophagus, diaphragm, and sling fibers contribute to the lower oesophageal sphincter pressure. The sling fibers of the cardia are located at the same depth as the circular muscle fibers of the esophagus.

Risk Factors for GERD

 GERD is usually caused by a transient relaxation of the LES and less commonly by a transient escalate in intraabdominal pressure or a low resting pressure of the LES. Specifically recognized peril factors for gastric regurgitation involve situations that cause lower esophageal sphincter incompetence (alcohol, nicotine, caffeine, multiple medications, and hiatal hernia), circumstances that antecedent escalated intra-abdominal pressure (obesity, pregnancy, straining, and bending), and situations that antecedent escalated gastric volume (heavy meals and intestinal obstruction). Alcohol consumption perhaps also escalates gastric acid secretion and delay gastric emptying, and NSAIDs perhaps interfere with PG cytoprotection [12]. Obstructive sleep apnoea and obesity predispose to nocturnal GERD, with more than 100 reflux episodes narrated during an 8 hr sleep in individuals afflicting from OSA [13, 14]. The consumption of spicy and acidic beverages and foods perhaps also exaggerate GERD problems. Extrinsic gastric compression from escalated visceral adiposity in overweight and obese patients perhaps also influence to escalated intragastric pressure and thus a suitable pressure gradient for reflux to happen [15]. Hiatus hernia: Hiatus hernia sequences from the replacement of the junction between the esophagus and the stomach (the gastroesophageal junction) which normally acts as an obstacle to reflux of stomach contents into the esophagus. Hiatus hernia is probably to be caused by weakening or destruction of the phrenoesophageal ligament. Patients with hiatus hernia have further episodes of reflux and further solemn reflux esophagitis [16]. Obesity: People who are overweight or obese (specifically with central adiposity) have a greater pitfall of advancing gastroesophageal reflux disorder, EE, Barrett’s esophagus, and esophageal adenocarcinoma. Central adiposity escalates gastric pressure, thus changing the pressure gradient across the gastroesophageal junction, which suits the advancement of reflux. Obese people are also most probably to advance hiatus hernia, influencing to gastroesophageal reflux disorder [16]. High-fat diet: Patients with GERD experience further episodes of reflux pursuing consumption of a high-fat meal analogized to a low-fat meal [16]. Tobacco smoking: There are multiple surveys relating tobacco smoking to the advancement of gastroesophageal reflux disorder. Escalated gastroesophageal reflux disorder peril is evident in recent and previous smokers. The peril of gastroesophageal reflux disorder escalates with the duration of smoking as well as the quantum of tobacco smoked [16]. Alcohol consumption: Chiefly, alcohol consumption is not consociated with an escalated peril of gastroesophageal reflux disorder. However, certain evidence does indicate that moderate to high alcohol consumption (greater than 7 alcoholic drinks per week) perhaps escalate gastroesophageal reflux disorder pitfall [16]. Helicobacter pylori infection: The link between Helicobacter pylori infection and advancement of PUD is currently well accepted. Evidence also indicates that Helicobacter pylori infection adds to the load of NSAID-associated gastroesophageal reflux disorder. Yet while diagnoses of gastroesophageal reflux disorder are escalating, the rate of Helicobacter pylori infection is decrement. A consociation between Helicobacter pylori and gastroesophageal reflux disorder symptoms is tenuous, with multiple surveys actually indicating a minimized pitfall of gastroesophageal reflux disorder in people infected with Helicobacter pylori. Also, Helicobacter pylorus does not seem to be consociated with the advancement of Barrett’s esophagus or esophageal adenocarcinoma; however, it is linked to gastric cancer. Evidence does not assist Helicobacter pylori eradication therapy for GERD management. Pregnancy gastroesophageal reflux disorder is narrated by 40%–85% of pregnant women. It is more probably linked to escalated progesterone causing relaxation of the LES. Pregnancy can precipitate gastroesophageal reflux disorder symptoms or worsen existing gastroesophageal reflux disorder. Onset of gastroesophageal reflux disorder is ubiquitously toward the end of the 1st trimester and often lasts throughout the remainder of gestation, usually worsening with gestational age. Symptoms often resolve after delivery. While symptoms can be severe, complications from gastroesophageal reflux disorder during pregnancy are not probably to advance [16]. Genetics: Evidence assists a genetic cause for gastroesophageal reflux disorder. Surveys display a consistent rate of gastroesophageal reflux disorder between identical twins of forty three percent and for non-identical twins of twenty six percent. Genetic testing also suggests an important link between gastroesophageal reflux disorder, Barrett’s esophagus, and esophageal adenocarcinoma [16]. Medications: A number of medications can antecedent gastroesophageal reflux disorder symptoms and/or esophageal damage involving: Medications that de-escalate LES pressure (antibiotics (eg, tetracyclines and clindamycin), statins, dopamine, estrogen, progesterone, angiotensin-converting enzyme inhibitors, bisphosphonates, vitamin C, clomipramine, anticholinergics, tricyclic antidepressants, corticosteroids (oral and inhaled), β-agonists, nitroglycerines, barbiturates, aminophylline, benzodiazepines, warfarin, cyproterone, ethinylestradiol, and dihydropyridine calcium channel blockers) and direct irritants to the esophageal mucosa (aspirin, nonsteroidal anti-inflammatory drugs, iron, quinidine, potassium chloride) [16]. Other risks: Consumption of coffee, tea, chocolate, garlic, onions, peppers, citrus products, tomato products, spicy foods, and carbonated beverages perhaps escalate gastroesophageal reflux disorder perils [16].

Management of GERD

The objective of anti-reflux managements is to effectively relieve gastroesophageal reflux disorder -related symptoms, cure and maintain remission of EE, prevent complications of gastroesophageal reflux disorder, decrease the frequency and duration of gastroesophageal reflux, and improve health-related quality of life.  The recent management for gastroesophageal reflux disorder includes of lifestyle modifications, pharmacological therapies, endoscopic procedures, and surgical interventions.

Lifestyle Modifications

The primary treatment of gastroesophageal reflux disorder involves lifestyle modifications, such as elevating the head of the bed, dietary modifications, restricting alcohol, and managing obesity. Lifestyle modifications remain the cornerstone of every therapeutic intervention for gastroesophageal reflux disorder, which is ubiquitously overlooked by physicians and not pursued by patients [17]. Avoid medications that exacerbate gastroesophageal reflux: anticholinergics, tricyclic and other antidepressants, calcium channel blockers, benzodiazepines. Avoid smoking or drinking alcohol: The cause of this heartburn might be a direct toxic effect of alcohol on the esophageal mucosa, and/or a reduction in LES pressure provoked by alcoholic beverages. Both alcoholic beverages (white wine and red wine) provoked an increase in the proportion of time at pH less than 4 in the lower esophagus. Smoking does have a negative influence on reflux mechanisms: it lowers LES pressure and has a negative impact on salivary bicarbonate secretion, thereby minimizing the neutralizing consequence of saliva on intra-oesophageal acid [18]. Smoking can cause aerophagia, which influences to escalated belching and regurgitation. Alcohol de-escalates LES pressure, and perhaps exacerbates symptoms such as heartburn. Avoid eating large fatty meals, spicy food, chocolate, peppermint, coffee, onions, and citrus juices: Sweets such as candy bars have been respected as antecedent reflux because of them have more osmolality and rich in fat content. Chocolate has also been revealed to cause reflux by de-escalating of the LES pressure [18]. Avoid carbonated beverages: carbonated beverages specifically appear to have a disadvantageous impact on reflux mechanisms, likely because of escalate in TLESRs or a reduction in the LES pressure [18]. Reduce weight (if overweight): obesity increases upper abdominal pressure, thereby provoking an increase in gastroesophageal reflux [18]. Excess fat around the belly increases intra-abdominal pressure. Avoid tight-fitting garments. Elevate the head of the bed: It has been stated for many years that individuals with typical GERD symptoms should sleep with the head in an elevated position in the bed, and that they should avoid the recumbent position for 3 h postprandial [18]. Place 6 to 8 in blocks under the head posts. Approximately 15 to 20 cm blocks, for patients who have symptoms while in a recumbent position decreases nocturnal esophageal acid contact time. Avoid assuming in supine position up to 3 hours after a meal/ eat small meals and avoid eating immediately prior to sleeping at least three hrs before bed, if possible and remain upright after meals. Avoid foods that de-escalate LES pressure: high-fat meal decreases LES pressure and high-protein, low-fat meal elevates or augment LES pressure and thus include protein-rich meals. Restrain foods with irritant outcomes on the esophageal mucosa. For mandatory medications that irritate the esophageal mucosa such as bisphosphonates, take in the upright position with copious of liquid.

Pharmacological therapies

Recently, PPIs and H2RAs, albeit with lower potency) represent the cornerstone of gastroesophageal reflux disorder management. Pharmacological treatment typically includes of the use of H2 blockers and, in consummate cases, PPIs. Although medical therapy with proton pump inhibitors is effective in consummate patients, there are escalating concerns respecting the long-term use of these medications. These involve interaction with a number of cardiac medicines such as clopidogrel [19], consociation with osteoporotic fractures [20], hospital-acquired diarrhea and pneumonia, hypomagnesemia, and vitamin B12 malabsorption [21]. Furthermore, extended proton pump inhibitors use has been consociated with chronic atrophic gastritis in patients infected with Helicobacter pylori [22]. In the recent years, a significant number of patients with GERD are found to be refractory to PPIs therapy despite even twice daily use of these medications [23].

Antacids and alginate: Al hydroxide, Mg hydroxide, Mg trisilicate all are OTC. Antacids decrease pepsinogen activity by maintaining the intragastric pH >4. Antacids Neutralize hydrochloric acid leading to increase in pH of the gastric contents. Alginate Precipitates to form a gel, which entraps CO2 to develop foam; the foam floats on the stomach contents, replaces the postprandial gastric acid pocket, and physically blocks refluxate from entering the esophagus; Alginates perhaps also coat and guard mucosal lining of esophagus [23-26, 18]. Short duration of action of antacids, necessitates frequent administration throughout the day to provide continuous acid neutralization, taking antacids after meals can escalate the duration of action from around1 to 3 hours, night time acid suppression cannot be maintained with bedtime doses of antacids, and typical doses are two tablets or 1 tablespoonful 4 times daily (after meals and at bedtime).

Histamine H2 receptor antagonists: H2 receptor antagonists such as cimetidine, ranitidine and famotidine are widely used and accepted for the management of gastrointestinal reflux disorder. All H2RAs are equally efficacious, selection of the specific agent for GERD should be depending on differences in PK, safety profile, and cost. Gastrin secretion after a meal influence to histamine release; Enliven of histamine H2 receptors influences to hydrochloric acid release via the hydrogen potassium ATPase (H+ -K+ -ATPase) proton pump; H2RAs are selective, competitive antagonists of histamine H2 receptors, suppressing both basal and enliven acid secretion produced by histamine release [24-27, 18]. Nonprescription H2RAs are effective in diminishing gastric acid secretion, when taken prior to meals. H2RAs in divided doses are effective for treating mild to moderate GERD.

Proton pump inhibitors (PPIs): PPI are so far the consummate powerful agents for the management of reflux esophagitis. These medications are effective in healing reflux esophagitis and relieving related symptoms. Commonly available PPIs drugs are: lansoprazole, omeprazole, pantoprazole, esomeprazole. Irreversibly inactivates the active form of the proton pump (H+ -K+ -ATPase), suppressing both stimulated and basal acid secretion produced by acetylcholine and histamine release; Accumulate at the luminal surface of the pump; Prodrugs that require acidic conversion to the active species; Acid labile and therefore in order to suppress premature activation their formulations are ubiquitously enteric coated; as PP attaching is irreversible, inhibition persists for up to 36 hours, well outlasting the plasma t1/2 of proton pump inhibitors (1–2 hours); takes up to 3 days of management for entire PPs to be obviated and for the inhibition of acid secretion to reach steady state [24-27, 18]. Proton pump inhibitors provide the greatest symptom relief, and the highest healing rates, especially for patients with EE, complicated symptoms (Barrett’s esophagus, strictures), non-erosive GERD with moderate to severe symptoms. Proton pump inhibitors are also efficacious in patient’s refractory to H2RAs. PPIs are superior to H2RAs in patients with moderate to severe gastroesophageal reflux disorder and should be given empirically to patients with troublesome symptoms.

Promotility/Prokinetic agents: Considering gastroesophageal reflux disorder is a disorder of intestinal motility and that delayed gastric emptying has been identified in certain patients with GERD, it follows those prokinetic agents perhaps of benefit. The fresher generation 5-HT4 selective agonist prucalopride, which does not have the cardiovascular toxicity of cisapride, perhaps ameliorate effective for gastroesophageal reflux disorder; however, clinical trials are lacking. The use of metoclopramide and domperidone for gastroesophageal reflux disorder is equally controversial [25]. Prokinetic agents such as domperidone can promote the peristalsis of smooth muscle in oesophagus and increase the LOS pressure. Thus gastric content reflux is obviated and gastric emptying is accelerated [28]. Promotility agents useful as adjuncts to acid inhibition therapy in patients with a known motility defect, such as, lower esophageal sphincter incompetence, de-escalated esophageal clearance, delayed gastric emptying.  Metoclopramide is a dopamine antagonist and a cholinomimetic that crosses the blood-brain. Food and drug administration confirmed for short-term use only. Barrier and neutralizes the inhibitory outcome of dopamine in the CNS and on the gastrointestinal (GI) smooth muscle. Metoclopramide, a dopamine antagonist, escalates LES pressure in a dose related manner, accelerates gastric emptying, it does not ameliorate esophageal clearance. Metoclopramide provides symptomatic improvement for certain patients with GERD.

Mucoprotective agents: Sucralfate is composed of basic aluminum salt of sucrose octa sulphate and provides mucosal protection by creating an adherent complex with the proteinaceous exudates of the denuded esophageal mucosa. It also has pepsin-attaching and bile acid binding capacities that enhance tissue resistance. The release of sucrose sulfate, which coats the injured esophageal mucosa during reflux, is dependent on the acidity of the stomach; therefore, its effectiveness will be based on both the stomach’s acidity and the simultaneous presence of the drug in the esophagus. Sucralfate has lost favor as an anti-reflux management because it has limited efficacy and requires multiple (qid) dosing.

Step-up, step-down, or step-in: In this step the cost perhaps increased in relation to proton pump inhibitors for the long-term management of gastroesophageal reflux disorder; consequently, variety of therapeutic approaches have been suggested to offset the cost. The step-up approach launches with lifestyle modifications and upgrade treatment depending on symptom response (OTC H2RA + H2RA full dose + PPI once daily, etc.). This conservative approach has taken the endorsement of institutions and third-party payers and is recently the consummate ubiquitously advocated. In contrast, the step-down approach suitable to initiate therapy with a PPI standard dose and stepping down to an H2RA. Ofman et al compared the step-up approach to the step-down approach (using initially the PPI test) and found that the latter approach resulted in ameliorated symptom relief and QOL over one year and further important utilization of invasive diagnostic testing at a small marginal increase in total cost. Furthermore, -80% of subjects on multiple dosing of PPIs were able to step down to a PPI once daily after 6 months’ follow-up on a single-dose PPI [29, 30]. Step-up approach, start with lifestyle modifications and patient-directed therapy and progress to pharmacologic management or anti-reflux surgery. Step-down approach, start with a PPI instead of an H2RA and then step down to the lowest acid suppression necessitated to control symptoms.

Endoscopic procedures: This technique is less invasive and safer than surgical fundoplication with the intention of achieving identical efficacy rates. In addition, there is de-escalated reliance on proton pump inhibitors or distinctive oral medications used for GERD. The original endoluminal therapies have been widely classified to 4 different types; (1) fixation, (2) ablation, (3) injection, (4) mucosal excision and suturing.

Surgical interventions: The objective of surgery is to construct a competent LOS by creating a valve between the lower oesophagus and the stomach and to correct any abnormal anatomy, such as hiatus hernia [31]. Surgical options for gastroesophageal reflux disorder also have their limitations involving escalated costs, hospitalization, up to 10% complication rate, and 28-day recovery [32]

Candidates for surgical therapy: Side effects from medical therapy; poor adherence with medical therapy; concern about or wish to withdraw chronic medical therapy; symptomatic with a large hiatal hernia regurgitation not interested in medical therapy abnormal pH test on maximum PPI dose; and symptoms correlate with nonacid reflux while on maximum PPI dose.

Surgical therapy is another treatment alternative for longterm therapy in patients with gastroesophageal reflux disorder and has become further appealing since the introduction of laparoscopic anti-reflux surgery. Indications for anti-reflux surgery, which typically involve laparoscopic fundoplication or bariatric surgery, involve unwillingness to remain on lifelong medical therapy, intolerance of medical therapy, medically refractory symptoms with evidence of gastroesophageal reflux disorder on endoscopy or pH monitoring, or gastroesophageal reflux disorder in the setting of a large hiatal hernia. The short- and medium-term effects of laparoscopic anti-reflux surgery are quite good in terms of ameliorating the typical symptoms of gastroesophageal reflux disorder [33]. Fundoplication surgery is the consummate ubiquitous surgery used to treat gastroesophageal reflux disorder. It perhaps used to treat gastroesophageal reflux disorder symptoms that have not been well restrained by medications. In fundoplication surgery, the fundus of the stomach is wrapped around the esophagus and sewn into place to strengthen the LES. Certain Comparatively fresh nonsurgical procedures used to manage gastroesophageal reflux disorder are still undergoing trials to ascertain their long-term safety and effectiveness. These involve Stretta radiofrequency procedure, in which radiofrequency energy is delivered through an endoscope to tighten the LES; and EndoCinch procedure, in which an endoscopic sewing device is used to make a series of sutures that adjusts the LES so that it blocks acid reflux more effectively [34].

Bariatric surgery has become one of the main managements for weight loss amid obese patients. Currently, the consummate ubiquitously performed bariatric surgeries are laparoscopic adjustable gastric banding, Roux en-Y gastric bypass, and laparoscopic sleeve gastrectomy. However, there have been elaborating concerns about side effects initiated by these surgical techniques, involving stenosis at the anastomosis site, stomal ulcer, fistula, band erosion, and motor dysfunction of the esophagus, stomach, and small bowel among others [35].

Conclusion

Gastroesophageal reflux (GER) delineated as the symptoms or mucosal damage sequencing from the abnormal retrograde movement of gastric contents from the stomach back up to the esophagus. The greater the length of this section, the further valve-like an outcome there is. 3rd, the angle between the stomach and the oesophagus (the angle of His) also supports to prevent reflux. The body has several mechanisms to protect the esophagus against the effects of acid reflux during the waking period. High-fat meal decrease LES pressure and high-protein, low-fat meal elevates or augment LES pressure and thus include protein-rich meals. Restrain foods with irritant consequences on the esophageal mucosa. Proton pump inhibitors irreversibly inactivates the active form of the proton pump (H+ -K+ -ATPase), suppressing both stimulated and basal acid secretion produced by acetylcholine and histamine release; Accumulate at the luminal surface of the pump.

Abbreviations

ACG: American College of Gastroenterology; EE: Erosive esophagitis; ERD: Erosive reflux disease; GERD: Gastroesophageal reflux disease; GI: Gastrointestinal; H2RAs: Histamine type 2 receptor antagonists; LES: Lower esophageal sphincter; LOS: Lower oesophageal sphincter; NERD: Non-erosive reflux disease; OTC: Over the counter; PPIs: Proton pump inhibitors

Acknowledgments

The author would be grateful to anonymous reviewers by the comments that increase the quality of this manuscript.

Data Sources: Sources searched include Google Scholar, Research Gate, PubMed, NCBI, NDSS, PMID, PMCID, Scopus database, Scielo and Cochrane database. Search terms included: definition, pathophysiology, risk factors, and management of gastroesophageal reflux disease

Availability of data and materials

The datasets generated during the current study are available with correspondent author.

Conflict of interest

The author has no financial or proprietary interest in any of material discussed in this article.

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