Effect of proton pump inhibitors on the risk and prognosis of infections in patients with cirrhosis and ascites

Background & Aims: Many patients with cirrhosis use proton pump inhibitors. We aimed to determine their effects on the risk and prognosis of infections in patients with cirrhosis and ascites. Methods: We used data from three 1-year trials of satavaptan treatment of ascites (N = 1198) to compare incidence and 90-day mortality of first-time infections between users and nonusers of proton pump inhibitors. With standard and marginal structural Cox models, we adjusted for differences in gender, age, cirrhosis aetiology, Model for End-stage Liver Disease score, serum albumin, lactulose use, severity of ascites, and history of spontaneous bacterial peritonitis or variceal bleeding. Results: During the follow-up, 446 patients had an infection. At inclusion, 524 patients (44%) used proton pump inhibitors, and 645 (54%) used them at some point during the follow-up. Proton pump inhibitor use increased the rate of infections overall (adjusted hazard ratio = 1.43, 95% CI 1.18-1.74), and it also increased the rate of all specific types of infections except upper respiratory tract infections of presumably viral origin. The estimated cumulative risk of infections was 36.4% for proton pump inhibitor users vs 25.1% for nonusers at 6 months (relative risk = 1.45, 95% CI 1.22-1.73), and 45.2% vs 37.7% at 1 year (relative risk = 1.20, 95% 0.97-1.40). Use of proton pump inhibitors did not affect mortality during the 90 days following infection (adjusted hazard ratio = 0.83, 95% CI 0.53-1.31). Conclusions: Approximately half of patients with cirrhosis and ascites use proton pump inhibitors. This use increases their risk of bacterial infections, but does not affect their prognosis after an infection occurs.