Systematic Review With Meta-analysis

Association of Helicobacter Pylori Infection With Gastro-oesophageal Reflux and its Complications

Mohammad Zamani; Shaghayegh Alizadeh-Tabari; Amir Hossein Hasanpour; Leonardo H. Eusebi; Alexander C. Ford


Aliment Pharmacol Ther. 2021;54(8):988-998. 

In This Article

Abstract and Introduction


Background: Conflicting results exist on the association between Helicobacter pylori infection and gastro-oesophageal reflux (GOR), and its complications, such as erosive oesophagitis (EO) and Barrett's oesophagus (BO).

Aims: To explore the association of H. pylori infection with GOR symptoms and their complications

Methods: We searched Embase, PubMed, Web of Science and Scopus databases through December 2020 for relevant articles. Regarding the association between H. pylori and GOR symptoms (heartburn, regurgitation or reflux), we included observational studies comparing the prevalence of GOR symptoms between H. pylori-positive and -negative individuals. Concerning the association between H. pylori and complications of GOR, we included studies comparing the prevalence of EO or BO between H. pylori-positive and -negative individuals.

Results: In total, 36 papers were eligible. Based on seven cross-sectional surveys, H. pylori infection was associated with a lower odds of GOR symptoms (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.61–0.90). However, in four case-control studies, H. pylori infection was not associated with odds of GOR symptoms (OR 1.10, 95% CI 0.85–0.1.43). In 26 cross-sectional studies in patients with GOR symptoms, the OR for EO was 0.70 (95% CI 0.58–0.84) in H. pylori-positive vs -negative cases. Based on nine cross-sectional studies in subjects with GOR complications, no significant association was found between H. pylori infection and either endoscopically-diagnosed (OR 1.84, 95% CI 0.67–5.02) or histologically confirmed (OR 0.85, 95% CI 0.60–1.20) BO.

Conclusions: Helicobacter pylori infection appears to be associated with a decreased odds of GOR symptoms and EO. In contrast, H. pylori infection did not seem to affect the odds of BO in patients with GER complications.


Gastro-oesophageal reflux disease (GORD) is one of the most common gastrointestinal disorders, particularly in western countries. Approximately 15% of the general population is affected by gastro-oesophageal reflux (GOR) symptoms, with a detrimental impact on quality of life among individuals who experience them, as well as a significant economic burden for the community.[1] The chronic nature of GOR symptoms can lead to the development of complications, mainly in the distal oesophagus, such as erosive oesophagitis (EO) or Barrett's oesophagus (BO), the precancerous condition for oesophageal adenocarcinoma.[2] Although the majority of patients who undergo endoscopic evaluation due to GOR symptoms demonstrate normal oesophageal mucosa, and are usually labelled as having non-erosive reflux disease (NERD), EO is found in up to 30% of GORD patients, and between 3% and 14% are found to have histologically-confirmed BO.[3,4] Many factors have been associated with an increased risk of GORD, and its complications, including alcohol consumption, presence of hiatus hernia, and obesity.[5–7]

Due to its pivotal role in gastric inflammation and carcinogenesis, Helicobacter pylori infection has also been evaluated as a possible factor related to oesophageal diseases. Infection with this bacterium has been inversely associated with GORD and BO, particularly the cagA+ strain, as it is thought that the resultant chronic gastritis reduces total acid production and, therefore, acid reflux.[8–10] Numerous studies have been conducted to assess the relationship between H. pylori infection and GOR with conflicting results, questioning whether H. pylori infection truly protects against the development of GOR and its complications. For instance, some studies alluded to a protective effect of H. pylori infection against GOR symptoms,[11,12] but others have not shown this effect.[13,14] Conflicting results were also reported concerning the relationship between BO and H. pylori by two meta-analyses; Wang et al found no clear association between H. pylori infection and BO pooling data from 12 case-control studies,[15] whereas Fischbach et al reported that H. pylori might be protective for BO.[16]

A considerable amount of data has been published in the interim, and a more recent meta-analysis by Erőss et al concluded that H. pylori infection was associated with a reduced risk of BO.[17] However, most of the studies included in this meta-analysis used control groups recruited opportunistically, or populations that would not be likely to provide a true background prevalence of H. pylori. To overcome these issues, we conducted a contemporaneous systematic review and meta-analysis of observational studies to examine the association between H. pylori infection and the presence of GOR symptoms. We also aimed to evaluate the association between H. pylori infection and GOR complications, specifically EO and BO.