Proton pump inhibitors impact on the severity and mortality of the acute-on-chronic liver failure: Andalusian multicentric prospective study

In this study, we considered all adults aged ≥18 years who were admitted with ACLF diagnosis to the seven participating hospitals from Andalucía in Spain, between august 2020 to 2023. The diagnosis of ACLF was stablish according to the European Association for the Study of the Liver (EASL) definition based on the CANONIC study and was calculated using the CLIF Consortium Organ Function score (CLIF-C-OFs) at admission and the CLIF Consortium ACLF score (CLIF-C-ACLFs) at admission, at 3 and 7 days as a prognosis score to determine the risk of 28-days mortality. Upon admission, patients were categorized as exposed or not exposed, based on chronic PPI consumption, which was defined as daily PPI intake for more than 3 months prior to the onset of ACLF.

Upon admission, data on age, gender, body mass index, comorbidities and chronic PPI intake, norfloxacin, rifaximin, lactulose, statins, antiaggregation and anticoagulation usage, the comorbidity and etiology of the cirrhosis were recorded. All of them had their CLIF-C-OFs calculated to establish the diagnosis, which included serum bilirubin and creatinine levels, the necessity of renal replacement treatment, international normalized ratio, the level of encephalopathy graded by the West-Haven classification, mean arterial pressure, the use of vasopressors, oxygen saturation and the need for mechanical ventilation. Liver function was evaluated with the Child-Pugh score and MELD-Na score. To evaluate the prognosis, the CLIF-C-ACLFs score was calculated at admission, 3 and 7 days of hospitalization, adding the age and the white-cell count to the CLIF-C-OF score. Liver, kidney and hematological function parameters were collected, along with admissions to intensive care unit, new hospitalizations for ACLF and mortality rates at 28 days, 3 months and 6 months post-admissions. The principal objective was to evaluate the potential impact of chronic PPI consumption on the severity of the ACLF. Secondary objectives included assessing its association with mortality and different types of decompensations within the ACLF.

本研究纳入了2020年8月至2023年期间，西班牙安达卢西亚地区7家参与医院收治的所有年满18周岁、确诊慢加急性肝衰竭（ACLF, Acute-on-Chronic Liver Failure）的成年患者。ACLF的诊断依据欧洲肝脏研究学会（EASL, European Association for the Study of the Liver）基于CANONIC研究制定的标准，并分别以入院时的慢性肝衰竭联盟器官功能评分（CLIF-C-OFs, CLIF Consortium Organ Function score），以及入院时、住院第3天和第7天的慢性肝衰竭联盟ACLF评分（CLIF-C-ACLFs, CLIF Consortium ACLF score）作为预后评分，用以评估28天死亡风险。入院时，研究人员根据患者的慢性质子泵抑制剂（PPI, Proton Pump Inhibitor）暴露情况，将其分为暴露组与非暴露组；慢性PPI暴露定义为ACLF发病前每日服用PPI超过3个月。
入院时，研究人员记录了患者的年龄、性别、体质量指数、合并症、慢性PPI服用情况、诺氟沙星（norfloxacin）、利福昔明（rifaximin）、乳果糖（lactulose）、他汀类药物（statins）、抗血小板聚集药物（antiaggregation）及抗凝药物（anticoagulation）使用情况，以及肝硬化的合并症与病因。所有患者均计算CLIF-C-OFs评分以明确诊断，该评分涵盖血清胆红素与肌酐水平、肾脏替代治疗需求、国际标准化比值、以西-哈文分级（West-Haven classification）评估的肝性脑病程度、平均动脉压、血管活性药物使用情况、血氧饱和度及机械通气需求。肝功能采用Child-Pugh评分（Child-Pugh score）与终末期肝病模型联合血清钠评分（MELD-Na score）进行评估。为评估预后，研究人员在入院时、住院第3天和第7天计算CLIF-C-ACLFs评分，该评分在CLIF-C-OFs评分基础上加入了年龄与白细胞计数。研究同时收集了肝脏、肾脏与血液学功能参数，以及重症监护病房（ICU, Intensive Care Unit）收治情况、ACLF相关再住院率，以及入院后28天、3个月和6个月的死亡率。本研究的主要目的为评估慢性PPI暴露对ACLF严重程度的潜在影响；次要目的包括分析慢性PPI暴露与死亡率及ACLF患者不同类型失代偿事件的相关性。