High-dose proton pump inhibitor treatment is associated with a higher mortality in cirrhotic patients: A multicentre study

Background: Proton pump inhibitors (PPI) are frequently used in patients with cirrhosis. Aims: This study aimed to determine whether PPI use is associated with the prognosis of cirrhotic patients. Methods: We conducted a multicentre retrospective cohort study involving 1485 patients who had experienced hepatic encephalopathy (HE) from 7 referral centres in Korea. The primary outcome was overall survival and secondary outcomes included the development of cirrhotic complications, including recurrent HE, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), and gastrointestinal bleeding. Patients treated with PPI with a mean defined daily dose (mDDD) ≥0.5 (high-dose PPI group) were compared to those treated with PPI of an mDDD < 0.5 (No or low-dose PPI group) for each outcome. Results: Among 1485 patients (median age, 61 years; male, 61%), 232 were assigned to the high-dose PPI group. High-dose PPI use was independently associated with a higher risk of death (adjusted HR [aHR] = 1.71, 95% confidence interval [CI] = 1.38–2.11, p < 0.001). This result was reproducible after propensity score-matching (PSM) (aHR = 1.90, 95% CI = 1.49–2.44, p < 0.001). High-dose PPI use was an independent risk factor of recurrent HE (before PSM: aHR = 2.04, 95% CI = 1.66–2.51, p < 0.001; after PSM: aHR = 2.16, 95% CI = 1.70–2.74, p < 0.001), SBP (before PSM: aHR = 1.87, 95% CI = 1.43–2.43, p < 0.001; after PSM: aHR = 1.76, 95% CI = 1.31–2.36, p = 0.002), HRS (before PSM: aHR = 1.48, 95% CI = 1.02–2.15, p = 0.04; after PSM: aHR = 1.47, 95% CI = 0.95–2.28, p = 0.09), and gastrointestinal bleeding (before PSM: aHR = 1.46, 95% CI = 1.12–1.90, p = 0.006; after PSM: aHR = 1.74, 95% CI = 1.28–2.37, p < 0.001). Conclusions: The use of high-dose PPI was independently associated with increased risks of mortality and cirrhotic complications.