Helicobacter pylori Infection and Eradication in Relation to Gastroesophageal Reflux Disease

The effect of Helicobacter pylori (H. pylori) infection and eradication on the risk of gastroesophageal reflux disease (GERD) is still unclear.

We conducted a systematic review with a comprehensive literature search in the bibliographic databases Embase, Medline, and Cochrane Library through May 2024. Random-effects meta-analyses estimated the pooled odds ratios (OR) for the associations of H. pylori infection and eradication with GERD risk in prospective studies. A two-sample Mendelian randomization analysis based on data from the FinnGen study assessed associations between genetically predicted levels of seven H. pylori antibodies, that is, immunoglobulin G (IgG) and six virulence factors (cytotoxin-associated gene A [CagA], Outer Membrane Protein [OMP], vacuolating cytotoxin A [VacA], urease A [UreA], catalase and GroEL), and GERD risk.

A total of 25 eligible studies were included. Meta-analysis combining data from three cohort studies and one nested case-control study indicated an inverse association between H. pylori infection and GERD (pooled OR = 0.58; 95% confidence interval [CI], 0.23-1.44). Meta-analysis of 18 cohort studies and three randomized controlled trials (RCTs) showed an increased risk of GERD after H. pylori eradication (pooled OR = 2.01; 95% CI, 1.44-2.81), and this association was stronger when specifically analyzing reflux esophagitis (pooled OR = 2.27; 95% CI, 1.57-3.29). No associations were found in Mendelian randomization analysis for any of the studied H. pylori antibodies. [Correction added on 7 August 2025, after first online publication: The Abstract section has been updated to correct the number of studies for eligible and cohort under the Results.] CONCLUSIONS: The study suggests that H. pylori infection is associated with a decreased risk of GERD and that H. pylori eradication increases the risk.