EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; Hospital Clínic, IDIBAPS and CIBERehd, Barcelona, Spain.
EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; Hospital Clínic, IDIBAPS and CIBERehd, Barcelona, Spain.
Gastroenterology. 2019 Jul;157(1):149-162. doi: 10.1053/j.gastro.2019.03.021. Epub 2019 Mar 22.
BACKGROUND & AIMS: We investigated the effect of albumin treatment (20% solution) on hypoalbuminemia, cardiocirculatory dysfunction, portal hypertension, and systemic inflammation in patients with decompensated cirrhosis with and without bacterial infections.
We performed a prospective study to assess the effects of long-term (12 weeks) treatment with low doses (1 g/kg body weight every 2 weeks) and high doses (1.5 g/kg every week) of albumin on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines, collecting data from 18 patients without bacterial infections (the Pilot-PRECIOSA study). We also assessed the effect of short-term (1 week) treatment with antibiotics alone vs the combination of albumin plus antibiotics (1.5 g/kg on day 1 and 1 g/kg on day 3) on plasma levels of cytokines in biobanked samples from 78 patients with bacterial infections included in a randomized controlled trial (INFECIR-2 study).
Circulatory dysfunction and systemic inflammation were extremely unstable in many patients included in the Pilot-PRECIOSA study; these patients had intense and reversible peaks in plasma levels of renin and interleukin 6. Long-term high-dose albumin, but not low-dose albumin, was associated with normalization of serum level of albumin, improved stability of the circulation and left ventricular function, and reduced plasma levels of cytokines (interleukin 6, granulocyte colony-stimulating factor, interleukin 1 receptor antagonist, and vascular endothelial growth factor) without significant changes in portal pressure. The immune-modulatory effects of albumin observed in the Pilot-PRECIOSA study were confirmed in the INFECIR-2 study. In this study, patients given albumin had significant reductions in plasma levels of cytokines.
In an analysis of data from 2 trials (Pilot-PRECIOSA study and INFECIR-2 study), we found that albumin treatment reduced systemic inflammation and cardiocirculatory dysfunction in patients with decompensated cirrhosis. These effects might be responsible for the beneficial effects of albumin therapy on outcomes of patients with decompensated cirrhosis. ClinicalTrials.gov, Numbers: NCT00968695 and NCT03451292.
我们研究了白蛋白治疗(20%溶液)对伴有和不伴有细菌感染的失代偿性肝硬化患者低白蛋白血症、心循环功能障碍、门静脉高压和全身炎症的影响。
我们进行了一项前瞻性研究,评估了低剂量(每 2 周 1 克/公斤体重)和高剂量(每周 1.5 克/公斤体重)白蛋白长期(12 周)治疗对血清白蛋白、血浆肾素、心循环功能、门静脉压和细胞因子血浆水平的影响,从 18 例无细菌感染的患者(先导性 PRECIOSA 研究)中收集数据。我们还评估了单独使用抗生素与白蛋白联合抗生素(第 1 天 1.5 克/公斤,第 3 天 1 克/公斤)短期(1 周)治疗对包括在随机对照试验(INFECIR-2 研究)中的 78 例细菌感染患者的生物库样本中细胞因子血浆水平的影响。
先导性 PRECIOSA 研究中许多患者的心循环功能障碍和全身炎症极其不稳定;这些患者的肾素和白细胞介素 6 血浆水平有强烈和可逆的峰值。长期高剂量白蛋白,但不是低剂量白蛋白,与血清白蛋白水平的正常化、循环和左心室功能稳定性的改善以及细胞因子(白细胞介素 6、粒细胞集落刺激因子、白细胞介素 1 受体拮抗剂和血管内皮生长因子)的血浆水平降低相关,而门静脉压无明显变化。在先导性 PRECIOSA 研究中观察到的白蛋白的免疫调节作用在 INFECIR-2 研究中得到了证实。在这项研究中,给予白蛋白的患者细胞因子的血浆水平显著降低。
在对两项试验(先导性 PRECIOSA 研究和 INFECIR-2 研究)的数据进行分析后,我们发现白蛋白治疗降低了失代偿性肝硬化患者的全身炎症和心循环功能障碍。这些作用可能是白蛋白治疗对失代偿性肝硬化患者结局有益的原因。ClinicalTrials.gov,编号:NCT00968695 和 NCT03451292。