One PPI may not fit all-prevalence of CYP2C19 phenotypes in patients with Barrett's esophagus

Barrett's esophagus (BE) is associated with longstanding gastroesophageal reflux disease and can progress to esophageal adenocarcinoma. BE is primarily managed with proton pump inhibitors (PPIs), which are metabolized by cytochrome P450 2C19 (CYP2C19). CYP2C19 polymorphisms affect PPI plasma levels, which are categorized as poor (PM), intermediate (IM), normal (NM), rapid (RM), and ultra-rapid (UM) metabolizers. This study assessed the prevalence of CYP2C19 phenotypes in patients with BE and concomitant hiatal hernias (HH).

This was a single-institution retrospective review of medically-managed adult BE patients with CYP2C19 genotyping. Patients were grouped by HH size (small, medium, or large). CYP2C19 phenotypes were stratified by genotype as: PM/IM, NM, and RM/UM based on anticipated need for PPI dose adjustment. Descriptive statistics and a multivariable analysis to determine factors associated with RM/UM were used.

A total of 97 patients (58% female, median age 61, mean BMI 27.5) were included, and CYP2C19 phenotypes were PM/IM (32%, 95% CI 0.27-0.41), NM (37%, 95% CI 0.27-0.47), and RM/UM (31%, 95% CI 0.22-0.40). HHs were present in 59 patients. Notably, 17% of RM/UM patients had concomitant severe erosive esophagitis, LA grade C/D. On sub-analysis, there was a trend toward higher prevalence of RM/UMs(53%) compared with PM/IM/NM (33%, p = 0.06) in patients who did not have a HH. The presence of HHs tended to be more frequent in the PM/IM/NMs (67%) compared with RM/UMs (47%, p = 0.06). On multivariable analysis, this trend persisted with HHs being less present with RM/UMs (OR 0.43, 95% CI 0.18-1.03).

There is a trend toward high prevalence of the RM/UM phenotype in patients with BE. Patients with RM/UM phenotype could benefit from PPI dose optimization. Given the poor survival associated with esophageal adenocarcinoma and its association with BE, assessing CYP2C19 phenotype to optimize PPI dosage and effectiveness could have significant public health implications, and additional prospective studies are needed.