PPIs linked to risk for severe infection, decompensation in patients with cirrhosis


Mahmud N, et al. Abstract OS126. Presented at: International Liver Congress; June 22-26, 2022; London (hybrid meeting).

Mahmud reports no relevant financial disclosures.

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LONDON — Exposure to proton pump inhibitors correlated with an increased risk for severe infection and cirrhosis decompensation among a subset of patients with cirrhosis, according to research presented at the International Liver Congress.

“The safety of PPIs in cirrhosis remains quite controversial,” Nadim Mahmud, MD, MS, MPH, MSCE, assistant professor of medicine and epidemiology at the University of Pennsylvania Perelman School of Medicine, told attendees. “There is conflicting data regarding the impact of PPIs on several key liver-related adverse events, including infections, decompensation and mortality. There is plausibility to this potential association. … However, prior studies are limited.”

Among patients with cirrhosis, PPI use correlated with an increased risk for: Cirrhosis decompensation, Severe infection

In a retrospective cohort study, Mahmud and colleagues included 76,251 patients with compensated cirrhosis from the Veterans Health Administration, of whom 23,628 were on PPI at baseline. Researchers time-updated PPI exposure every 30 days and used inverse probability treatment weighting and Cox regression analysis to evaluate incidence of infection, decompensation and all-cause mortality, adjusting for time-updated cardiovascular comorbidities, statin use, antiplatelet medication and hospitalization for gastrointestinal bleed.

According to study results, PPI use was associated with a reduced risk for mortality among patients hospitalized for GI bleeds (HR = 0.88; 95% CI, 0.84-0.92) but was not associated with all-cause mortality among patients who were not hospitalized for GI bleeds (HR = 0.99; 95% CI, 0.97-1.02).

However, PPI use was associated with an increased risk for cirrhosis decompensation (HR = 1.64; 95% CI, 1.61-1.68) and severe infection (HR = 1.21; 95% CI, 1.18-1.24) with risk increasing with higher dose exposure. The strongest observed infection association was with spontaneous bacterial peritonitis (HR = 1.77; 95% CI, 1.66-1.88), where PPI use correlated with a 77% increased risk.

“PPI exposure is associated with severe infections and cirrhosis decompensation in this broad cohort of veterans in the United States,” Mahmud concluded. “This observation may mediate the observed association between PPI exposure and liver-related mortality.

“In summary, PPIs should not be avoided solely due to concerns of liver-related adverse events. However, their prescription should be limited to appropriate indications at the lowest effective dose.”

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