IRCSS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Centre for Applied Biomedical Research-CRBA, Alma Mater Studiorum University of Bologna, St. Orsola Hospi, tAlbologna, Italy.
Hepatology. 2021 Oct;74(4):2058-2073. doi: 10.1002/hep.31798. Epub 2021 May 26.
Circulating albumin in cirrhosis can be dysfunctional because of accumulating structural damages, leading to the concept of effective albumin concentration (eAlb), referring to the albumin portion presenting structural and functional integrity. We aimed to estimate eAlb in patients with decompensated cirrhosis and analyze its relationships with albumin function and clinical outcomes as compared to total albumin concentration (tAlb).
We evaluated 319 patients with cirrhosis hospitalized for acute decompensation (AD) with and without acute-on-chronic liver failure (ACLF) and 18 age- and sex-comparable outpatients with compensated cirrhosis. tAlb was quantified by standard assay, whereas eAlb was estimated combining liquid chromatography/electrospray ionization/mass spectrometry and standard methods. Albumin binding and detoxification efficiency were evaluated by electron paramagnetic resonance analysis. Circulating albumin in patients with decompensated cirrhosis displayed multiple structural abnormalities, with reversible oxidation and glycation being the most frequent. As a result, eAlb progressively declined with the worsening of cirrhosis and was superior to tAlb in stratifying patients between compensated cirrhosis, AD, and ACLF, as well as patients with and without complications. Moreover, eAlb, but not tAlb, was closely associated with binding capacities in ACLF. Finally, eAlb at admission predicted the occurrence of ACLF within 30 days and mortality at 90 days better than tAlb.
This large, observational study provides the evidence in patients with decompensated cirrhosis that eAlb can be quantified and differentiated from tAlb routinely measured in clinical practice. As compared to tAlb, eAlb is more closely associated with disease severity and albumin dysfunction and carries a greater prognostic power. These results prompt future research assessing eAlb as a biomarker for predicting prognosis and treatment response.
肝硬化患者循环中的白蛋白可能因结构损伤而功能失调，由此产生有效白蛋白浓度（eAlb）的概念，指的是具有结构和功能完整性的白蛋白部分。我们旨在评估失代偿期肝硬化患者的 eAlb，并分析其与白蛋白功能以及与总白蛋白浓度（tAlb）相比的临床结局的关系。
我们评估了 319 例因急性失代偿（AD）和/或慢加急性肝衰竭（ACLF）住院的肝硬化患者和 18 例年龄和性别相匹配的代偿期肝硬化门诊患者。tAlb 通过标准检测方法进行定量，而 eAlb 通过液相色谱/电喷雾电离/质谱与标准方法相结合进行估计。通过电子顺磁共振分析评估白蛋白结合和解毒效率。失代偿期肝硬化患者的循环白蛋白显示出多种结构异常，其中最常见的是可逆氧化和糖化。结果，eAlb 随着肝硬化的恶化而逐渐下降，在将代偿期肝硬化、AD 和 ACLF 患者以及有无并发症的患者分层方面优于 tAlb。此外，与 ACLF 相关的结合能力与 eAlb 密切相关，而不是 tAlb。此外，入院时的 eAlb 比 tAlb 更能预测 30 天内发生 ACLF 和 90 天内的死亡率。
这项大型观察性研究为失代偿期肝硬化患者提供了证据，即 eAlb 可以通过常规临床实践中测量的 tAlb 进行定量和区分。与 tAlb 相比，eAlb 与疾病严重程度和白蛋白功能障碍更密切相关，具有更大的预后价值。这些结果促使未来研究评估 eAlb 作为预测预后和治疗反应的生物标志物。
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