Host Genetic Determinants Associated With Helicobacter pylori Eradication Treatment Failure: A Systematic Review and Meta-analysis
Abstract
Background & aims: Helicobacter pylori infects approximately 50% of individuals worldwide. Successful H pylori eradication is associated with reduced risk of gastric cancer and peptic ulcer disease, among other conditions. We hypothesized that host genetic determinants, especially those affecting gastric pH, might contribute to eradication therapy failure, particularly when treatment adherence and antibiotic susceptibility are confirmed. We aimed to conduct a meta-analysis of host genetic variants associated with H pylori eradication failure.
Methods: We searched the literature for studies comparing posttreatment H pylori eradication failure vs success (outcome) according to host genetic polymorphisms (exposure). Reference groups were defined according to genotypes (or corresponding phenotypes) hypothesized to be associated with successful eradication. We pooled estimates using a random-effects model and performed comprehensive sensitivity analyses.
Results: We analyzed 57 studies from 11 countries; the vast majority analyzed CYP2C19 polymorphisms. Among individuals prescribed eradication regimens with proton pump inhibitors predominantly CYP2C19 metabolized, enhanced vs poor metabolizer phenotypes were associated with a 2.52-fold significantly higher likelihood of eradication failure and 4.44-fold significantly higher likelihood when treatment adherence and H pylori clarithromycin susceptibility (if relevant) were confirmed. There was no association between CYP2C19 variants…
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Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.
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