摘要:背景及目的 急性肝衰竭患者病死率高，常常需要肝移植进行治疗，现有的可以对急性肝衰竭进行预测的指标有限，M30，一种细胞角蛋白酶-18的裂解产物，在死亡或是需进行肝移植的急性肝衰竭患者的血清标本中的水平明显升高。通过对血浆中M30的水平和其他的常规临床变量进行联合监测，我们设计了一种新的预测ALF的预测指标（称之为急性肝衰竭研究指数ALFSG），针对该指标的准确性，我们将其与 KCC 和MELD模型进行比较，同时我们在另一组独立的急性肝衰竭患者中对我们提出的模型进行验证。方法 在250名急性肝衰竭患者入院后的前四天测定3次血清中的M30和M65抗原水平（整体的细胞角蛋白酶-18的片段，一种凋亡和坏死的指标），同时对入院后第一天测定的相关因素进行回归分析，用于判断下列因素是否与肝移植或是患者的死亡存在相关性，主要包括：年龄、病因、昏迷指数、国际标准化比值、血浆PH、身高体重指数、肌酐水平、胆红素、血磷,、动脉血氨、乳酸，M30及M65的对数值。对ALFSG及其他相关指标进行受试者工作曲线下面积的计算。结果 在研究入口阶段：昏迷指数，INR，胆红素和血磷的水平，M30的对数值被认为是鉴别需要进行肝移植或是死亡的患者的最为精确的指标。ALFSG指数鉴别这些患者的敏感性及特异性分别为85.6% 和64.7%。基于受试者工作曲线的比较，ALFSG指数 (AUROC, 0.822)在鉴别需进行肝移植或是死亡患者时优于KCC (AUROC, 0.654) 或 MELD (AUROC, 0.704) (P值分别是 0.0002 和0.0010,).，在对另外250名独立的急性肝衰竭的患者的分析中，我们的模型也得到了证实。结论 ALFSG指数，是临床指标与凋亡生物标记物M30测定的结合，与KCC及MELD相比，对于ALF的预后评价有更好的预测价值。
吉林大学第一医院肝胆胰内科 张明媛 摘译
本文首次发表于[Gastroenterology. 2012 Aug 8. [Epub ahead of print]]
Development of an Accurate Index for Predicting Outcomes of Patients With Acute Liver Failure
Abstract BACKGROUND & AIMS:Patients with acute liver failure (ALF) have high mortality and frequently require liver transplantation (LT); few reliable prognostic markers are available. Levels of M30, a cleavage product of cytokeratin-18 caspase, are significantly increased in serum samples from patients with ALF who die or undergo LT. We developed a prognostic index for ALF based on level of M30 and commonly measured clinical variables (called the Acute Liver Failure Study Group [ALFSG] index) and compared its accuracy with that of the King's College criteria (KCC) and Model for End Stage Liver Disease (MELD). We also validated our model in an independent group of patients with ALF. METHODS: Serum levels of M30 and M65 antigen (the total cytokeratin-18 fragment, a marker of apoptosis and necrosis) were measured on 3 of the first 4 days following admission of 250 patients with ALF. Logistic regression was used to determine whether the following factors, measured on day 1, were associated with LT or death: age, etiology; coma grade; international normalized ratio (INR); serum pH; body mass index; levels of creatinine, bilirubin, phosphorus, arterial ammonia, and lactate; and log(10) M30 and log(10) M65. The area under the receiver operating characteristic (AUROC) was calculated for the ALFSG and other indices. RESULTS: Coma grade, INR, levels of bilirubin and phosphorus, and log(10) M30 value at study entry most accurately identified patients who would require LT or die. The ALFSG index identified these patients with 85.6% sensitivity and 64.7% specificity. Based on comparison of AUROC values, the ALFSG Index (AUROC, 0.822) better identified patients most likely to require LT or die than the KCC (AUROC, 0.654) or MELD (AUROC, 0.704) (P = .0002 and P = .0010, respectively). We validated these findings in a separate group of 250 patients with ALF. CONCLUSIONS: The ALFSG index, a combination of clinical markers and measurements of the apoptosis biomarker M30, better predicts outcomes of patients with ALF than the KCC or MELD; ClinicalTrials.gov, number NCT00518440.
