Helicobacter pylori Infection and Barrett's Esophagus: A Systematic Review and Meta-Analysis
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OBJECTIVES: The majority of distal esophageal adenocarcinomas are believed to arise in patients with Barrett's esophagus (BE). Helicobacter pylori (H. pylori) infection plays an etiological role in gastric carcinogenesis, but any possible role in BE is uncertain. We aimed to explore the possible relationship between H. pylori infection and BE by meta-analysis. METHODS: Observational studies comparing the prevalence of H. pylori infection in patients with BE and healthy controls conducted in adult populations and published in all languages were identified through MEDLINE, EMBASE, and Cochrane database searches up to week 5, 2008. H. pylori infection had to be confirmed by histology and/or serology and/or RUT and/or culture. Studies were excluded if no raw data for outcomes of interest were available or controls were patients with disease or duplicate publications. Summary effect size was calculated as odds ratio (OR) and 95% confidence intervals (CIs) by the random-effects model using Review Manager 4.2.8. RESULTS: Of 519 citations identified, a total of 12 case-control studies compared the prevalence of H. pylori infection in BE (n=550) and controls (9 studies included controls with normal endoscopy and 3 studies used healthy blood donors as control, n=2,979). There was no significant difference in the overall prevalence of H. pylori infection between BE and controls (42.9% vs. 43.9%, OR=0.74, 95% CI 0.40-1.37, P=0.34), but with significant heterogeneity. Subgroup analysis showed that the prevalence of H. pylori infection was significantly lower in BE than in endoscopically normal healthy controls (23.1% vs. 42.7%, OR=0.50, 95% CI 0.27-0.93, P=0.03) with significant heterogeneity observed between studies. The heterogeneity was eliminated by excluding a single Asian outlier study. In contrast, H. pylori infection was significantly increased in BE patients in the three studies using healthy blood donors as "normal controls" (71.2% vs. 48.1%, OR=2.21, 95% CI 1.07-4.55). In BE patients, the prevalence of H. pylori infection was significantly lower in the esophagus than in the stomach (3.3% vs. 24.7%, OR=0.14, 0.03-0.67) in three studies. CONCLUSIONS: H. pylori infection and BE are inversely related when compared with endoscopically normal controls but not blood donor controls. Limited evidence suggests that there is no clear association between H. pylori infection and BE. To determine more accurately the effect size of H. pylori infection in BE, high quality prospective case-control studies with age-matched, endoscopically normal healthy controls are needed.