Surg Endosc. 2026 Jun 5. doi: 10.1007/s00464-026-12904-4. Online ahead of print.
ABSTRACT
INTRODUCTION: Gastroesophageal Reflux Disease (GERD) is treated primarily with proton pump inhibitors (PPIs), with surgery reserved for patients refractory to PPIs or with symptomatic hiatal hernias. PPI efficacy depends on metabolism by cytochrome P450 2C19 (CYP2C19) in the liver, which varies with genetic polymorphisms. Rapid (RM) and ultra-rapid (UM) metabolizers may require higher PPI doses for efficacy, while poor (PM) and intermediate (IM) metabolizers respond to lower doses but have higher risk of side effects. This study assesses CYP2C19 phenotype prevalence in medically versus surgically managed GERD. We hypothesized a higher RM/UM rate among surgical patients, suggesting PPI resistance.
METHODS: This was a multi-site retrospective cohort study of adult patients with GERD and CYP2C19 genotyping from 2012 to 2023. Medical patients included those with Barrett’s esophagus, LA grade C/D esophagitis, or abnormal pH testing. Surgical patients included those who underwent anti-reflux surgery. CYP2C19 phenotypes were grouped as PM/IM, normal metabolizer (NM), and RM/UM based on the anticipated need for PPI dose adjustment. Descriptive statistics were used for analysis.
RESULTS: A total of 261 patients were included in this study: 187 medical (female: 59%, mean age: 57 (SD 15), 77% White) and 74 surgical (female: 69%, mean age: 58 (SD 13), 89% White). Medical patients included the following esophageal pathologies: 52% Barrett’s esophagus, 31% abnormal pH testing, and 17% LA grade C/D esophagitis. Surgical patients had a significantly higher proportion of RM/UM phenotypes compared to medical patients (p = 0.018). There was also a significant difference in hiatal hernia size between medical and surgical patients (p < 0.001).
CONCLUSION: Surgical patients have a higher prevalence of hypermetabolizing (RM/UM) CYP2C19 phenotypes compared to medical patients. Dose escalation of PPI should be considered in medical patients with these phenotypes, and if ineffective, a timely referral for anti-reflux surgery should be made.
PMID:42247133 | DOI:10.1007/s00464-026-12904-4
