Systematic Review With Meta-analysis

Risk Factors for Barrett's Oesophagus in Individuals With Gastro-oesophageal Reflux Symptoms

Leonardo H. Eusebi; Andrea Telese; Giovanna G. Cirota; Rehan Haidry; Rocco M. Zagari; Franco Bazzoli; Alexander C. Ford


Aliment Pharmacol Ther. 2021;53(9):968-976. 

In This Article

Abstract and Introduction


Background: Gastro-oesophageal reflux is considered the main risk factor for Barrett's oesophagus. The role of other potential risk factors for the development of Barrett's oesophagus in patients with gastro-oesophageal reflux symptoms is controversial.

Aims: To perform a systematic review and meta-analysis examining risk factors in development of Barrett's oesophagus.

Methods: Medline, Embase and Embase Classic were searched (until December 2020) to identify cross-sectional studies reporting prevalence of Barrett's oesophagus based on presence of one or more proposed risk factors in individuals with gastro-oesophageal reflux symptoms. Prevalence of Barrett's oesophagus was compared according to presence or absence of each risk factor in individuals with gastro-oesophageal reflux symptoms.

Results: Of 7164 citations evaluated, 13 studies reported prevalence of Barrett's oesophagus in 11 856 subjects. Pooled prevalence of histologically confirmed Barrett's oesophagus in individuals with gastro-oesophageal reflux symptoms in all studies was 7.0% (95% CI 4.8% to 9.6%). Prevalence was higher in subjects with hiatal hernia (OR 2.74; 95% CI 1.58 to 4.75) and in those who drank alcohol (OR 1.51; 95% CI 1.17 to 1.95). Other features including non-steroidal anti-inflammatory drugs and/or aspirin use (OR 1.19; 95% CI 1.00 to 1.42), smoking (OR 1.14; 95% CI 0.96 to 1.35) or obesity (OR 1.10; 95% CI 0.92 to 1.33) were not significantly associated with Barrett's oesophagus.

Conclusions: The prevalence of Barrett's oesophagus in individuals with gastro-oesophageal reflux symptoms was higher in those who drank alcohol, although this association was modest. The strongest association found was between hiatal hernia and Barrett's oesophagus. Other potential risk factors assessed in this study did not appear to be associated with presence of Barrett's oesophagus among individuals with gastro-oesophageal symptoms.


Gastro-oesophageal reflux symptoms are common in the community, affecting up to 15% of the general population, with striking variations depending on geographical region.[1] Other than the considerable impact of reflux symptoms on the quality of life of individuals who experience them,[2] the presence of chronic symptoms can lead to the development of Barrett's oesophagus and oesophageal adenocarcinoma.[3] Indeed, the presence of gastro-oesophageal reflux is one of the most frequent indications for endoscopic examination of the upper gastrointestinal tract, primarily to exclude the presence of associated lesions, such as erosive esophagitis or Barrett's oesophagus. However, only 3% to 14% of individuals who undergo endoscopy due to gastro-oesophageal reflux symptoms are found to have histologically confirmed Barrett's oesophagus, with a significantly higher prevalence in men.[4]

Several risk factors for gastro-oesophageal reflux symptoms have been reported, including age ≥50 years, tobacco smoking, non-steroidal anti-inflammatory drug (NSAID) and/or aspirin use, and obesity, although many of these associations are modest.[1] However, the association between Barrett's oesophagus and such risk factors is less clear, and their role in the development of BO is controversial, with conflicting evidence from existing studies.[5–8] In addition, these risk factors might represent confounders associated with increased gastro-oesophageal reflux, rather than being independently associated with the development of Barrett's oesophagus.

Several case-control studies and meta-analyses have evaluated the role of risk factors in the development of Barrett's oesophagus, but these have been conducted mainly in healthy individuals in the general population, so the role of these risk factors in individuals with gastro-oesophageal reflux symptoms is uncertain.[5–7,9] Systematic analysis of studies that report these types of data is important to allow physicians consulting with patients with gastro-oesophageal reflux symptoms to provide more precise estimates of the impact of potential risk factors for Barrett's oesophagus, as well as to identify areas where further research is needed. We therefore conducted a systematic review and meta-analysis examining the association between proposed risk factors and presence of Barrett's oesophagus, to evaluate their impact in patient with gastro-oesophageal reflux symptoms.