Helicobacter pylori and gastroesophageal reflux disease

INTRODUCTION — 

Helicobacter pylori is an important risk factor for the development of peptic ulcer disease, gastric adenocarcinoma, and primary B cell lymphoma of the stomach. A role for H. pylori in the pathogenesis of gastroesophageal reflux disease (GERD) has also been suggested. However, the link between GERD and H. pylori is complex.

This topic review summarizes the available evidence suggesting a role for H. pylori in GERD. The pathophysiology of GERD and the treatment of H. pylori are discussed separately. (See "Pathophysiology of gastroesophageal reflux disease" and "Treatment of Helicobacter pylori infection in adults".)

EPIDEMIOLOGY — 

Epidemiologic data show that as the prevalence of H. pylori decreased in Western societies, the prevalence of GERD, Barrett’s esophagus, and esophageal adenocarcinoma increased, leading to speculation of a causal relationship [1,2]. A network meta-analysis including 16 studies found that H. pylori infection was associated with lower odds of GERD (odds ratio [OR] 0.68; 95% CI 0.52-0.90), Barrett’s esophagus (OR 0.59; 95% CI 0.45-0.77), and esophageal adenocarcinoma (OR 0.54; 95% CI 0.39-0.74) [2].

Some studies suggest a role for the cytotoxin-associated gene A (cagA+) in the inverse relationship between H. pylori and Barrett’s esophagus [3,4]. CagA+ H. pylori is associated with corpus-predominant- and pan-gastritis [5] as well as gastric adenocarcinoma (see "Helicobacter pylori: Epidemiology, pathophysiology, and overview of disease associations", section on 'Gastric malignancy'). In a case-control study of 533 United States veterans undergoing colorectal cancer screening, seropositivity for cagA+ H. pylori strains was inversely associated with Barrett’s esophagus (OR 0.36; 95% CI 0.14-0.90) and showed a trend toward an inverse association with erosive esophagitis (OR 0.47; 95% CI 0.21-1.03) [5].

PATHOPHYSIOLOGY OF THE H. PYLORI-GERD INTERACTION — 

The pathophysiology of gastroesophageal reflux disease (GERD) depends on the balance between factors that damage (or sensitize) the esophageal mucosa (eg, excessive mucosal exposure time to caustic refluxate) and those that preserve it (eg, a competent esophagogastric junction [EGJ] and normal esophageal acid clearance) (see "Pathophysiology of gastroesophageal reflux disease"). Hence, from a population perspective, one would not anticipate an association between H. pylori infection and GERD. Data supporting the lack of association between H. pylori infection and GERD include the following:

●A cross-sectional study of 1916 patients undergoing endoscopy for dyspeptic symptoms found that smoking, increased body mass index, older age, hiatus hernia, and peptic ulcer disease were independently associated with erosive esophagitis, but H. pylori infection was not [6].

●In a healthy screening population of 10,102 individuals in Korea, reflux symptoms were not associated with H. pylori infection or eradication [7].

The primary mechanism by which H. pylori might modulate clinical manifestations of GERD is by modifying gastric acid secretion and, hence, the content of the gastric refluxate. This effect differs depending on the predominant location of H. pylori infection (eg, antral-dominant versus corpus-dominant or pangastritis) (figure 1).

Antral-dominant gastritis — Antral-dominant H. pylori infection increases serum gastrin levels and suppresses somatostatin secretion, which normally inhibits gastrin secretion. This, in turn, increases gastric acid secretion and leads to a corresponding increased acidity of gastroesophageal reflux, which exacerbates its injurious potential in the esophagus. In particular, those infected with H. pylori strains containing the dupA gene exhibit intense antral inflammation, less gastric atrophy, an increased risk of duodenal ulcer, and relative protection against gastric cancers [8]. (See "Helicobacter pylori: Epidemiology, pathophysiology, and overview of disease associations", section on 'Peptic ulcer disease (PUD)'.)

Corpus-dominant and pangastritis — H. pylori infection associated with corpus-dominant or pangastritis is associated with gastric mucosal atrophy and a decreased gastric acid secretory capacity that might protect against GERD. Illustrative of this relationship, in a large study of more than 25,000 Korean patients undergoing health checkups, serologic atrophic gastritis (measured by pepsinogen I/II ratio) was associated with a reduced risk of esophagitis (OR 0.49, 95% CI 0.28-0.87) [9]. Similarly, endoscopic atrophic gastritis correlated inversely with esophagitis occurrence and severity.

EFFECT OF H. PYLORI ERADICATION ON GERD — 

The effect of H. pylori eradication on gastroesophageal reflux disease (GERD) varies depending on the location of H. pylori infection and its clinical manifestations, including duodenal ulcer and corpus-dominant gastritis. Conflicting reports on the effect of H. pylori eradication on GERD can be explained by the failure to account for H. pylori’s variable effects on gastric acid secretion (see 'Pathophysiology of the H. pylori-GERD interaction' above). In addition, the period of observation in most of these studies may have been too short to allow for physiological equilibration.  

Patients with duodenal ulcers — The preponderance of the evidence suggests that in individuals with duodenal ulcers, H. pylori eradication does not significantly affect GERD. Duodenal ulcers are associated with antrum-dominant H. pylori gastritis and increased gastric acid secretion, both of which improve or normalize following H. pylori eradication. However, because excessive acid secretion is not a major factor in the pathophysiology of GERD, one would not anticipate that H. pylori eradication would significantly improve or worsen GERD (see "Pathophysiology of gastroesophageal reflux disease"). Data supporting this hypothesis include the following:

●In a post-hoc analysis of eight trials of H. pylori therapy involving 1165 participants with duodenal ulcer disease, eradication of H. pylori was not associated with the development of erosive esophagitis, new symptomatic GERD, or worsening GERD symptoms in patients with pre-existing GERD [10].

●A systematic review of 27 studies found no evidence that H. pylori eradication in patients with duodenal ulcer provoked reflux esophagitis or worsened heartburn [11].

Patients with corpus-dominant or pangastritis — In patients with H. pylori-associated atrophic gastritis, treatment of H. pylori infection may unmask latent GERD. Corpus-dominant H. pylori infection can lead to atrophic gastritis and reduced acid secretion, and several investigators have observed that GERD is less common in patients with severe corpus gastritis [12,13]. In this circumstance, H. pylori eradication may result in increased acid secretion. This was demonstrated by a study of 68 patients with GERD who underwent H. pylori eradication and found that esophageal acid exposure time as measured by pH-metry increased from 23.6 percent before to 37.4 percent after eradication [14].

In individuals with corpus gastritis, gastritis improvement after H. pylori treatment is associated with an increased risk of incident GERD, which may be heightened by the presence of other GERD risk factors. In a study of 572 H. pylori-positive patients, H. pylori eradication was associated with the development of GERD [15]. Incident GERD was additionally associated with severe corpus gastritis and hiatus hernia, a known GERD risk factor. (See "Pathophysiology of gastroesophageal reflux disease".)

Patients with pre-existing GERD — Patients with pre-existing GERD necessarily have preserved acid secretion and the compromised physiology associated with GERD (ie, disruption of the antireflux barrier). H. pylori eradication should not significantly worsen acid reflux in such patients and may improve it in patients with antral-dominant gastritis [16].

INTERACTION OF H. PYLORI AND CHRONIC PPI THERAPY — 

Proton pump inhibitor (PPI) treatment alters the distribution of H. pylori in the stomach causing corpus-dominant gastritis with decreased gastric acid secretion. Hence, patients on long-term PPI therapy are at increased risk for the development of atrophic gastritis and, potentially, gastric cancer [17].  

Controlled trials have demonstrated that H. pylori eradication in patients with reflux esophagitis receiving long-term PPI therapy decreases inflammation and reverses corpus gastritis [18,19]. Consequently, consensus guidelines from Europe, Japan, and the Italian Society of Gastroenterology suggest testing for H. pylori in patients receiving long-term acid suppression with PPIs [20-22].

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Acid reflux and GERD in adults (The Basics)" and "Patient education: H. pylori infection (The Basics)")

●Beyond the Basics topics (see "Patient education: Gastroesophageal reflux disease in adults (Beyond the Basics)" and "Patient education: Helicobacter pylori infection and treatment (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Epidemiologic data show that as the prevalence of H. pylori decreased in Western societies, the prevalence of gastroesophageal reflux disease (GERD), Barrett’s esophagus, and esophageal adenocarcinoma increased, leading to speculation of a causal relationship. (See 'Epidemiology' above.)

●Impact of H. pylori on gastric acid secretion – The primary mechanism by which H. pylori might modulate clinical manifestations of GERD is by modifying gastric acid secretion and, hence, the content of the gastric refluxate. However, this effect can increase or decrease gastric acid secretion, depending on whether the gastritis is antral-dominant or corpus-dominant, respectively (figure 1). (See 'Pathophysiology of the H. pylori-GERD interaction' above.)

●Effects of H. pylori eradication

•Patients with duodenal ulcer – Eradication of H. pylori is the standard of care in people with peptic ulcer disease. (See "Peptic ulcer disease: Treatment and secondary prevention", section on 'Eradicate Helicobacter pylori (H. pylori) infection'.)

Eradication of H. pylori may decrease acid secretion in patients with duodenal ulcer, who usually have antral-dominant gastritis. However, excessive acid secretion is not a major factor in the pathophysiology of GERD, and one would not anticipate any significant effect of H. pylori eradication on GERD in duodenal ulcer patients (figure 1). (See 'Patients with duodenal ulcers' above and "Pathophysiology of gastroesophageal reflux disease", section on 'Mechanisms of gastroesophageal reflux disease'.)

•Patients with corpus-dominant or pangastritis – Eradication of H. pylori may increase acid secretion in patients with atrophic gastritis who have corpus-dominant or pangastritis. This potentially unmasks latent GERD that was being “treated” by atrophic gastritis and the associated reduced acid secretion (figure 1). (See 'Patients with corpus-dominant or pangastritis' above and "Pathophysiology of gastroesophageal reflux disease".)

•Patients with pre-existing GERD – For patients with pre-existing GERD, available data do not demonstrate worsening disease with H. pylori eradication. In fact, GERD may be improved in individuals with antral-dominant gastritis. (See 'Patients with pre-existing GERD' above.)

●Patients on chronic PPI therapy – In people who chronically take proton pump inhibitors (PPIs), H. pylori infection is associated with an increased risk for the development of atrophic gastritis and, potentially, gastric cancer. Eradication of H. pylori in these patients decreases inflammation and reverses corpus gastritis, leading some authorities to recommend testing for and eradicating H. pylori in these patients. (See 'Interaction of H. pylori and chronic PPI therapy' above.)

ACKNOWLEDGMENT — 

We are saddened by the death of Mark Feldman, MD, who passed away in March 2024. UpToDate gratefully acknowledges Dr. Feldman's role as Section Editor on this topic and his dedicated and longstanding involvement with the UpToDate program.