Alterations in the Functional Capacity of Albumin in Patients with Decompensated Cirrhosis Is Associated with Increased Mortality
Alterations in the Functional Capacity of Albumin in Patients with Decompensated Cirrhosis Is Associated with Increased Mortality
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DOI：
10.1002/hep.22913
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发表时间：
2009-08-01
期刊：
影响因子：
13.5
通讯作者：
Davies, Nathan A.
中科院分区：
文献类型：
--
作者：
Jalan, Rajiv;Schnurr, Kerstin;Davies, Nathan A.
肝功能衰竭患者白蛋白浓度降低。白蛋白输注可提高肝硬化合并自发性细菌性腹膜炎患者的生存率，据推测这可能部分归因于其解毒能力。本研究的目的是对肝硬化患者的白蛋白功能进行详细的定量和定性评估。纳入健康对照组和肝硬化急性恶化需要住院的患者（n = 34）。使用自旋标记（16羟基硬脂酸酯）滴定法和电子顺磁共振波谱法对脂肪酸结合位点的亲和力进行白蛋白功能评估，并测量缺血修饰白蛋白（IMA）。22例患者出现急性慢性肝衰竭。12例采用分子吸附剂再循环系统（MARS）治疗，10例采用标准药物治疗。对于测量的每个参数，患者的白蛋白功能能力降低，随着疾病的严重程度而恶化。15例患者死亡，以白蛋白比率（IMAR）表达的IMA在非幸存者中明显高于幸存者（P < 0.001；受试者工作曲线下面积= 0.8）。map治疗后患者的白蛋白功能未见改变。观察到IMAR与位点I和2的脂肪酸结合系数呈显著负相关（P均< 0.001），表明可能存在与蛋白质相关的位点。结论：本研究结果表明，晚期肝硬化患者存在明显的白蛋白功能障碍，并进一步证明了循环白蛋白的损害，而MARS治疗并不能逆转这种损害。IMAR与疾病严重程度相关，可能在急性慢性肝衰竭中具有预后作用。(肝脏病学50:555 2009;564)。
Albumin concentration is diminished in patients with liver failure. Albumin infusion improves survival of cirrhotic patients with spontaneous bacterial peritonitis, and it is hypothesized that this may be due in part to its detoxifying capabilities. The aim of this study was to perform detailed quantitative and qualitative assessment of albumin function in patients with cirrhosis. Healthy controls and patients with acute deterioration of cirrhosis requiring hospital admission (n = 34) were included. Albumin function was assessed using affinity of the fatty acid binding sites using a spin label (16 doxyl-stearate) titration and electron paramagnetic resonance spectroscopy and ischemia-modified albumin (IMA) was measured. Twenty-two patients developed acute-on-chronic liver failure. Twelve were treated with the Molecular Adsorbents Recirculating System (MARS) and 10 with standard medical therapy. For each parameter measured, the patients' albumin had reduced functional ability, which worsened with disease severity. Fifteen patients died, and IMA, expressed as an albumin ratio (IMAR), was significantly higher in nonsurvivors compared with survivors (P < 0.001; area under the receiver operating curve = 0.8). No change in the patients' albumin function was observed following MAPS therapy. A significant negative correlation between IMAR and the fatty acid binding coefficients for sites I and 2 (P < 0.001 for both) was observed, indicating possible sites of association on the protein. Conclusion: The results of this study suggests marked dysfunction of albumin function in advanced cirrhosis and provide further evidence for damage to the circulating albumin, which is not reversed by MARS therapy. IMAR correlates with disease severity and may have prognostic use in acute-on-chronic liver failure. (HEPATOLOGY 2009;50:555-564.)