Team 8, Hepatic complications of obesity, INSERM, U895, Nice, France.
PLoS One. 2011 Mar 18;6(3):e17599. doi: 10.1371/journal.pone.0017599.
Quantification of hepatocyte death is useful to evaluate the progression of alcoholic liver diseases. Our aims were to quantify and correlate the circulating levels of Cytokeratin 18 (CK18) and its caspases-generated fragment to disease severity in heavy alcoholics.
METHODOLOGY/PRINCIPAL FINDINGS: CK18 and CK18-fragment were evaluated in the serum of 143 heavy alcoholics. Serum levels of markers of hepatocyte death (CK18), apoptosis (CK18 fragment) and necrosis (CK18 -CK18 fragment) increased in patients with severe fibrosis compared to patients with mild fibrosis. These markers strongly correlated with Mallory-Denk bodies, hepatocyte ballooning, fibrosis and with hepatic TNFα and TGFβ assessed in the liver of 24 patients. Elevated levels of serum hepatocyte death and apoptotic markers were independent risk factors in predicting severe fibrosis in a model combining alkaline phosphatase, bilirubin, prothrombin index, hyaluronate, hepatocyte death and apoptotic markers. The level of markers of hepatocyte death and apoptosis had an area under the receiving operator curve that predicted severe fibrosis of 0.84 and 0.76, respectively.
CONCLUSION/SIGNIFICANCE: Death of hepatocytes can be easily evaluated with serum markers and correlated with severe fibrosis in heavy alcohol drinkers. These biomarkers could be useful to rapidly evaluate liver injuries and the efficacy of therapies.
肝细胞死亡的量化对于评估酒精性肝病的进展非常有用。我们的目的是定量检测并分析血液中细胞角蛋白 18（CK18）及其半胱天冬酶剪切片段的水平，以评估重度酗酒者的疾病严重程度。
方法/主要发现：我们检测了 143 名重度酗酒者血清中的 CK18 和 CK18 片段。与轻度纤维化患者相比，严重纤维化患者的血清肝细胞死亡标志物（CK18）、凋亡标志物（CK18 片段）和坏死标志物（CK18-CK18 片段）水平升高。这些标志物与 Mallory-Denk 小体、肝细胞气球样变、纤维化以及 24 例患者肝组织中 TNFα 和 TGFβ 均具有强相关性。在一个包含碱性磷酸酶、胆红素、凝血酶原指数、透明质酸、肝细胞死亡和凋亡标志物的模型中，血清肝细胞死亡和凋亡标志物水平升高是预测严重纤维化的独立危险因素。肝细胞死亡和凋亡标志物预测严重纤维化的曲线下面积分别为 0.84 和 0.76。
结论/意义：可以通过血清标志物来评估肝细胞死亡，并且可以与重度酗酒者的严重纤维化相关联。这些生物标志物可用于快速评估肝损伤和治疗效果。
