UCL Institute for Liver and Digestive Health, London, UK.
Comprehensive Clinical Trials Unit, University College London, London, UK.
Clin Transl Gastroenterol. 2022 May 1;13(5):e00476. doi: 10.14309/ctg.0000000000000476.
Albumin is recommended in decompensated cirrhosis, and studies have shown potential immunomodulatory effects. However, 2 large trials of repeated albumin infusions demonstrated contrasting results between outpatients and hospitalized patients. We investigated markers of systemic inflammation, immune function, albumin binding, and cardiovascular function using samples from Albumin To prevenT Infection in chronic liveR failurE (ATTIRE) taken at baseline, day 5, and day 10 of the trial to identify why targeted albumin infusions had no effect in hospitalized patients.
Plasma samples were analyzed from 143 patients (n = 71 targeted albumin; n = 72 standard care at baseline) for cytokines, cardiovascular markers, prostaglandin E2, the effect of plasma on macrophage function, and albumin radioligand binding and oxidation status. The sample size was based on our feasibility study, and samples were selected by a trial statistician stratified by the serum albumin level and the presence of infection at randomization and analyses performed blinded to the study arm. Data were linked to 3-month mortality and treatment groups compared.
Increased baseline model for end-stage liver disease score, white cell count, calprotectin, CD163, tumor necrosis factor, renin, atrial natriuretic peptide, and syndecan-1 were associated with 3-month mortality. Despite infusing substantially differing volumes of albumin, there were no significant differences in inflammatory markers, albumin-prostaglandin E2 binding, or cardiovascular markers between treatment arms.
Contrary to many preclinical studies, targeted intravenous albumin therapy in hospitalized decompensated cirrhosis had no effect across a broad range of systemic inflammation, albumin function, and cardiovascular mediators and biomarkers compared with standard care, consistent with the null clinical findings.
在失代偿性肝硬化中推荐使用白蛋白，并且已有研究表明其具有潜在的免疫调节作用。然而，两项大型白蛋白重复输注试验在门诊和住院患者中显示出了截然不同的结果。我们通过Albumin To prevenT Infection in chronic liveR failurE（ATTIRE）试验中的基线、第 5 天和第 10 天的样本，研究了全身性炎症、免疫功能、白蛋白结合和心血管功能的标志物，以确定为何靶向性白蛋白输注对住院患者没有效果。
对 143 名患者（n=71 例靶向性白蛋白；n=72 例标准护理）的血浆样本进行了分析，以检测细胞因子、心血管标志物、前列腺素 E2、血浆对巨噬细胞功能的影响，以及白蛋白放射性配体结合和氧化状态。样本量是基于我们的可行性研究确定的，根据基线时的血清白蛋白水平和随机分组时感染的存在，由试验统计学家对样本进行分层随机选择，并进行盲法分析。将数据与 3 个月死亡率和治疗组进行了关联和比较。
基线时终末期肝病模型评分、白细胞计数、钙卫蛋白、CD163、肿瘤坏死因子、肾素、心房利钠肽和 syndecan-1 升高与 3 个月死亡率相关。尽管输注了大量不同体积的白蛋白，但治疗组之间在炎症标志物、白蛋白-前列腺素 E2 结合或心血管标志物方面均无显著差异。
与许多临床前研究相反，与标准护理相比，靶向性静脉内白蛋白治疗在住院失代偿性肝硬化患者中并未对全身性炎症、白蛋白功能和心血管介质和生物标志物产生广泛影响，这与无效的临床发现一致。
