Gastroenterology. 2022 Apr 6:S0016-5085(22)00352-3. doi: 10.1053/j.gastro.2022.03.052. Online ahead of print.
BACKGROUND AND AIMS: The impact of proton pump inhibitory (PPI) medications on adverse outcomes in cirrhosis remains controversial. We aimed to evaluate the association between PPI exposure and all-cause mortality, infection, and decompensation in a large national cohort.
METHODS: This was a retrospective study of patients with cirrhosis in the Veterans Health Administration. PPI exposure was classified as a time-updating variable from the index time of cirrhosis diagnosis. Inverse probability treatment weighting-adjusted Cox regression was performed with additional adjustment for key time-varying covariates including cardiovascular comorbidities, gastrointestinal bleeding (GIB), and statin exposure.
RESULTS: Of 76,251 included patients, 23,628 were on a PPI at baseline. In adjusted models, binary (yes/no) PPI exposure was associated with reduced hazard of all-cause mortality in patients with hospitalization for GIB (HR 0.88, 95% CI 0.84-0.91, p<0.001) but had no significant association in all others (HR 0.99, 95% CI 0.97-1.02, p=0.58. However, cumulative PPI exposure was associated with increased mortality in patients without hospitalization for GIB (HR 1.07 per 320mg-months [omeprazole-equivalents], 95% CI 1.06-1.08, p<0.001). PPI exposure was significantly associated with severe infection (HR 1.21, 95% CI 1.18-1.24, p<0.001) and decompensation (HR 1.64, 95% CI 1.61-1.68, p<0.001). In a cause-specific mortality analysis, PPI exposure was associated with increased liver-related mortality (HR 1.23, 95% CI 1.19-1.28), but decreased non-liver-related mortality (HR 0.88, 95% CI 0.85-0.91).
CONCLUSION: PPI exposure is associated with increased risk of infection and decompensation in cirrhosis, which may mediate liver-related mortality. However, PPI usage was associated with reduced all-cause mortality in those with prior GIB, suggesting benefit in the presence of an appropriate indication.