Giannone Ferdinando A, Domenicali Marco, Baldassarre Maurizio, Bartoletti Michele, Naldi Marina, Laggetta Maristella, Bertucci Carlo, Colecchia Antonio, Viale Pierluigi, Bernardi Mauro, Caraceni Paolo
U.O. Semeiotica Medica, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
Center for Applied Biomedical Research (C.R.B.A.), S.Orsola-Malpighi University Hospital, Bologna, Italy.
Liver Int. 2015 Nov;35(11):2425-32. doi: 10.1111/liv.12860. Epub 2015 May 21.
BACKGROUND & AIMS: Patients with cirrhosis present structural changes of human serum albumin (HSA) affecting non-oncotic functions. Ischaemia-modified albumin (IMA), which reflects the capacity to bind cobalt, has been associated to patient mortality during acute-on-chronic liver failure. This study aimed to assess whether circulating IMA is elevated in advanced cirrhosis and its relationship with severity of cirrhosis and specific complications.
A total of 127 cirrhotic patients hospitalized for an acute complication of the disease and 44 healthy controls were enrolled. Plasma IMA and IMA to albumin ratio (IMAr) were measured with a cobalt-binding assay. HSA isoforms carrying post-transcriptional molecular changes were assessed with HPLC-ESI-MS. The effect of endotoxemia on IMA was evaluated in rats with CCl4 -cirrhosis.
IMA/IMAr is significantly higher in cirrhotic patients than in controls, but no correlations were found with prognostic scores. IMA did not correlate with the altered HSA isoforms. Ascites, renal impairment and hepatic encephalopathy did not influence IMA/IMAr levels. In contrast, IMA/IMAr is significantly higher in infected than non-infected patients. ROC curves showed that IMA/IMAr had similar discriminating performances for bacterial infection as C-reactive protein (CRP). Moreover, CRP and IMA were independently associated with bacterial infection. Consistently, endotoxin injection significantly increased IMA in cirrhotic, but not in healthy rats.
IMA is elevated in patients with advanced cirrhosis. The IMA level does not correlate with disease severity scores, but it is specifically associated to bacterial infection, showing a discriminating performance similar to CRP. Further investigations to assess IMA as a novel diagnostic test for bacterial infection are advocated.
肝硬化患者存在影响非胶体渗透压功能的人血清白蛋白（HSA）结构变化。反映钴结合能力的缺血修饰白蛋白（IMA）与慢加急性肝衰竭患者的死亡率相关。本研究旨在评估晚期肝硬化患者循环中的IMA是否升高及其与肝硬化严重程度和特定并发症的关系。
共纳入127例因该病急性并发症住院的肝硬化患者和44例健康对照。采用钴结合试验检测血浆IMA和IMA与白蛋白比值（IMAr）。用高效液相色谱-电喷雾质谱法评估携带转录后分子变化的HSA异构体。在四氯化碳诱导肝硬化的大鼠中评估内毒素血症对IMA的影响。
肝硬化患者的IMA/IMAr显著高于对照组，但与预后评分无相关性。IMA与改变的HSA异构体无相关性。腹水、肾功能损害和肝性脑病不影响IMA/IMAr水平。相比之下，感染患者的IMA/IMAr显著高于未感染患者。ROC曲线显示，IMA/IMAr对细菌感染的鉴别性能与C反应蛋白（CRP）相似。此外，CRP和IMA与细菌感染独立相关。同样，内毒素注射显著增加了肝硬化大鼠的IMA，但未增加健康大鼠的IMA。
晚期肝硬化患者的IMA升高。IMA水平与疾病严重程度评分无关，但与细菌感染特异性相关，显示出与CRP相似的鉴别性能。提倡进一步研究评估IMA作为细菌感染的新型诊断试验。
