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Multicenter Study
. 2024 Apr;59(8):973-983.
doi: 10.1111/apt.17909. Epub 2024 Feb 22.

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

Jun Sik Yoon  1 , Ji Hoon Hong  2 , Soo Young Park  3 , Seung Up Kim  4 , Hwi Young Kim  5 , Ju Yeon Kim  2 , Moon Haeng Hur  2 , Min Kyung Park  2 , Yun Bin Lee  2 , Han Ah Lee  5 , Gi-Ae Kim  6 , Dong Hyun Sinn  7 , Sung Jae Park  1 , Youn Jae Lee  1 , Yoon Jun Kim  2 , Jung-Hwan Yoon  2 , Jeong-Hoon Lee  2
Affiliations
Multicenter Study

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

Jun Sik Yoon et al. Aliment Pharmacol Ther. 2024 Apr.

Abstract

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.

Keywords: bacterial translocation; hepatic encephalopathy; mean defined daily dose; spontaneous bacterial peritonitis.

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