Helicobacter pylori Infection and Eradication in Relation to Gastroesophageal Reflux Disease

ABSTRACT 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 24 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 17 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. Conclusions The study suggests that H. pylori infection is associated with a decreased risk of GERD and that H. pylori eradication increases the risk.