Does Continuous PPI Use Increase the Risk of Enteric Viral Infections?

Patients on continuous proton pump inhibitor (PPI) therapy may be at increased risk of developing acute gastroenteritis during the winter season, when the circulation of enteric viruses is highest, according to findings from a recent matched cohort study. 

While previous research has reported an association between continuous PPI use and an increased risk of acute bacterial enteric infections, there is limited evidence assessing the relationship between continuous PPI exposure and acute gastroenteritis of viral origin. This study aimed to evaluate the association between continuous PPI therapy and the occurrence of acute gastroenteritis when enteric virus circulation is at its peak. 

The Longitudinal Treatment Dynamic database, a drug dispensing database containing data on patients from a large number of community pharmacies in France, was accessed for this investigation. “Each patient exposed to continuous PPI therapy was matched to 3 unexposed patients, according to year of birth, sex, and identifiable regular panel pharmacy,” the study authors explained. 

The main outcome of the study was the occurrence of ≥1 episode of acute gastroenteritis during an epidemic in the winter of 2015 to 2016. An algorithm based on dispensing data that had been previously validated was used to identify episodes of acute gastroenteritis. Analysis included calculation of the relative risks of acute gastroenteritis, which were adjusted for age, gender, and treatments for chronic conditions. 

The analysis included a total of 233,596 patients who received PPI treatment continuously and 626,887 patients who did not receive PPI treatment; baseline demographics of the groups were well matched. Findings of the study revealed that 1.3% of patients that received PPI therapy (n=3131) experienced at least 1 epidemic episode of acute gastroenteritis compared with 0.7% of patients who did not receive PPI therapy (n=4327). Additionally, the adjusted relative risks of acute gastroenteritis for patients with continuous PPI exposure were reported to be 1.81 (95% CI 1.72, 1.90) for patients of all ages, 1.66 (95% CI 1.54, 1.80) for patients 45 to 64 years old, 2.19 (95% CI 1.98, 2.42) for patients 65 to 74 years old, and 1.98 (95% CI 1.82, 2.15) for patients ≥75 years old. 

“Despite the limitations related to exposure and outcome ascertainment and potential residual confounding, the results reported in this study support the hypothesis that continuous PPI use is associated with an increased risk of infections with enteric viruses and motivate the need for further studies to confirm this association and investigate the pathophysiological mechanisms,” the authors concluded.

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