Abstract：
BACKGROUND: Proton pump inhibitors (PPI) are frequently used in patients with cirrhosis.
OBJECTIVE: 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.
OBJECTIVE: 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.
摘要：
背景：质子泵抑制剂（PPI）经常用于肝硬化患者。
目的：本研究旨在确定PPI的使用是否与肝硬化患者的预后相关。
方法：我们进行了一项多中心回顾性队列研究，纳入了来自韩国7个转诊中心的1485例肝性脑病（HE）患者。主要结局是总生存率，次要结局包括肝硬化并发症的发展。包括反复发作的HE,自发性细菌性腹膜炎（SBP），肝肾综合征（HRS），和消化道出血.对于每个结果，将平均定义日剂量（mDDD）≥0.5的PPI治疗患者（高剂量PPI组）与mDDD<0.5的PPI治疗患者（无或低剂量PPI组）进行比较。
结果：在1485名患者中（中位年龄，61岁；男性，61%），232人被分配到高剂量PPI组。高剂量PPI使用与较高的死亡风险独立相关（校正后HR[aHR]=1.71，95%置信区间[CI]=1.38-2.11，p<0.001）。该结果在倾向评分匹配(PSM)后是可重复的(aHR=1.90,95%CI=1.49-2.44,p<0.001)。高剂量PPI使用是HE复发的独立危险因素（PSM前：aHR=2.04，95％CI=1.66-2.51，p<0.001；PSM后：aHR=2.16，95％CI=1.70-2.74，p<0.001），SBP(PSM前:aHR=1.87,95%CI=1.43-2.43,p<0.001;PSM后:aHR=1.76,95%CI=1.31-2.36,p=0.002),HRS（PSM前：aHR=1.48，95%CI=1.02-2.15，p=0.04；PSM后：aHR=1.47，95%CI=0.95-2.28，p=0.09），和消化道出血（PSM前：aHR=1.46，95％CI=1.12-1.90，p=0.006；PSM后：aHR=1.74，95％CI=1.28-2.37，p<0.001）。
结论：大剂量PPI的使用与死亡率和肝硬化并发症的风险增加独立相关。
目的：本研究旨在确定PPI的使用是否与肝硬化患者的预后相关。
方法：我们进行了一项多中心回顾性队列研究，纳入了来自韩国7个转诊中心的1485例肝性脑病（HE）患者。主要结局是总生存率，次要结局包括肝硬化并发症的发展。包括反复发作的HE,自发性细菌性腹膜炎（SBP），肝肾综合征（HRS），和消化道出血.对于每个结果，将平均定义日剂量（mDDD）≥0.5的PPI治疗患者（高剂量PPI组）与mDDD<0.5的PPI治疗患者（无或低剂量PPI组）进行比较。
结果：在1485名患者中（中位年龄，61岁；男性，61%），232人被分配到高剂量PPI组。高剂量PPI使用与较高的死亡风险独立相关（校正后HR[aHR]=1.71，95%置信区间[CI]=1.38-2.11，p<0.001）。该结果在倾向评分匹配(PSM)后是可重复的(aHR=1.90,95%CI=1.49-2.44,p<0.001)。高剂量PPI使用是HE复发的独立危险因素（PSM前：aHR=2.04，95％CI=1.66-2.51，p<0.001；PSM后：aHR=2.16，95％CI=1.70-2.74，p<0.001），SBP(PSM前:aHR=1.87,95%CI=1.43-2.43,p<0.001;PSM后:aHR=1.76,95%CI=1.31-2.36,p=0.002),HRS（PSM前：aHR=1.48，95%CI=1.02-2.15，p=0.04；PSM后：aHR=1.47，95%CI=0.95-2.28，p=0.09），和消化道出血（PSM前：aHR=1.46，95％CI=1.12-1.90，p=0.006；PSM后：aHR=1.74，95％CI=1.28-2.37，p<0.001）。
结论：大剂量PPI的使用与死亡率和肝硬化并发症的风险增加独立相关。
