Helicobacter pylori Infection and Eradication in Relation to Gastroesophageal Reflux Disease.

BACKGROUND AND

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

METHODS: 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.

RESULTS: 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.