Proton pump inhibitor (PPI) exposure is associated with an increased risk for infection and decompensation in patients with cirrhosis and with reduced all-cause mortality in those with previous gastrointestinal bleeding (GIB), according to a study in Gastroenterology.
The retrospective cohort study used data from the Veterans Health Administration (VHA) to examine the associations between PPI exposure and severe infection, decompensation, all-cause mortality, and cause-specific mortality in patients with compensated cirrhosis.
Participants had a new diagnosis of cirrhosis in the Veterans Outcomes and Costs Associated with Liver Diseases cohort from January 2008 to June 2021.
The primary exposure was PPI usage, defined as a filled prescription in the 90 days before the index date, and subsequently classified as usage in 30-day time-updated intervals throughout the follow-up. The primary outcome was all-cause mortality obtained from the Vital Status File.
A total of 76,251 patients with cirrhosis were included, of whom 23,628 (21.0%) were on a PPI at baseline. Compared with patients without PPI exposure (n=24,607, 32.3%), patients on a PPI at baseline were more often White (64.4% vs 60.0%, P <.001) and had more metabolic and cardiovascular comorbidities (each P <.001).
PPI exposure was associated with lower all-cause mortality in patients hospitalized with GIB after an interaction term between PPI exposure and hospitalization for GIB was added in the analysis (hazard ratio [HR], 0.88; 95% CI, 0.84-0.92, P <.001), but it was not significantly associated with all-cause mortality in the other patients (HR, 0.99; 95% CI, 0.97-1.02; P =.58).
In the categorical dose exposure model, time-updated 40-mg omeprazole equivalents compared with 0 mg were associated with a 7% increased hazard of mortality (HR, 1.07; 95% CI 1.03-1.10; P <.001). In the cumulative exposure model, each additional 320-mg months of PPI exposure (omeprazole equivalents) was associated with a 7% increased hazard of mortality (HR, 1.07; 95% CI, 1.06-1.08; P <.001).
Binary PPI exposure was associated with an increased hazard of severe infection in inverse probability treatment weighting Cox regression analysis (HR, 1.21 binary PPI exposure; 95% CI, 1.18-1.24; P <.001), and the hazard increased with greater PPI dose exposure. Binary PPI exposure also was associated with an increased risk for cirrhosis decompensation relative to no PPI exposure (HR, 1.64; 95% CI, 1.61-1.68; P <.001).
PPI exposure in patients without GIB was associated with a 12% decrease in the hazard of nonliver-related mortality (cause-specific HR [csHR], 0.88; 95% CI, 0.85-0.91), and it was associated with a 23% increase in the hazard of liver-related mortality (csHR, 1.23; 95% CI, 1.19-1.28).
The investigators noted that residual confounding is likely, and they were not able to explicitly adjust for specific indications for PPI prescription. Also, there was some degree of misclassification of exposure and outcomes, and the VHA cohort is primarily male with a high burden of metabolic, cardiovascular, and psychosocial comorbidities.
“These findings suggest that PPIs should not be avoided solely based on concerns of liver-related adverse outcomes, though prescriptions should be limited to appropriate indications at the lowest effective dose,” the researchers noted.
Disclosure: One of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.