Enomoto Masahide, Takaya Hiroaki, Namisaki Tadashi, Fujinaga Yukihisa, Nishimura Norihisa, Sawada Yasuhiko, Kaji Kosuke, Kawaratani Hideto, Moriya Kei, Akahane Takemi, Inoue Takashi, Matsumoto Masanori, Yoshiji Hitoshi
Department of Gastroenterology, Nara Medical University, Kashihara, Nara, Japan.
Institute for Clinical and Translational Science, Nara Medical University Hospital, Kashihara, Nara, Japan.
Hepatol Res. 2022 Apr;52(4):390-400. doi: 10.1111/hepr.13743. Epub 2022 Jan 8.
Acute-on-chronic liver failure (ACLF) is associated with a high risk of short-term mortality after progression to multiple organ failure. A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) is a metalloproteinase that specifically cleaves multimeric von Willebrand factor (VWF). An imbalance between ADAMTS13 enzyme and VWF substrate is associated with liver cirrhosis progression that induces ACLF. This study examined the relationship between ADAMTS13 and VWF and ACLF development to determine whether ADAMTS13 and VWF are useful predictive biomarkers for ACLF development and prognosis of patients with liver cirrhosis.
The study enrolled 67 patients with Child-Pugh class A and B liver cirrhosis. ADAMTS13 activity (ADAMTS13:AC) and VWF antigen (VWF:Ag) were measured using enzyme-linked immunosorbent assays. The ratio of VWF:Ag to ADAMTS13:AC (VWF:Ag/ADAMTS13:AC) was used to divide patients into two groups according to the classification and regression tree based on Gray model survival analysis.
Compared with patients with Child-Pugh class A liver cirrhosis, class B patients had a higher VWF:Ag/ADAMTS13:AC and a higher risk of ACLF development. Cumulative incidence of ACLF was significantly higher in patients with high (>7.9) versus low (≤7.9) VWF:Ag/ADAMTS13:AC (hazard ratio [HR], 6.50; 95% CI, 2.31-18.29; p < 0.001). Cumulative survival was significantly lower in cirrhotic patients with high versus low VWF:Ag/ADAMTS13:AC (HR 5.11; 95% CI, 1.85-14.14; p = 0.002).
For patients with liver cirrhosis, VWF:Ag/ADAMTS13:AC is associated with functional liver reserve and predicts the development of ACLF and the prognosis.
慢加急性肝衰竭（ACLF）进展为多器官功能衰竭后短期死亡率风险很高。含Ⅰ型血小板反应蛋白基序的解聚素样金属蛋白酶13（ADAMTS13）是一种特异性裂解多聚体血管性血友病因子（VWF）的金属蛋白酶。ADAMTS13酶与VWF底物之间的失衡与诱导ACLF的肝硬化进展相关。本研究探讨ADAMTS13与VWF及ACLF发生之间的关系，以确定ADAMTS13和VWF是否为ACLF发生及肝硬化患者预后的有用预测生物标志物。
本研究纳入67例Child-Pugh A级和B级肝硬化患者。采用酶联免疫吸附测定法测量ADAMTS13活性（ADAMTS13:AC）和VWF抗原（VWF:Ag）。根据基于Gray模型生存分析的分类回归树，使用VWF:Ag与ADAMTS13:AC的比值（VWF:Ag/ADAMTS13:AC）将患者分为两组。
与Child-Pugh A级肝硬化患者相比，B级患者的VWF:Ag/ADAMTS13:AC更高，发生ACLF的风险更高。VWF:Ag/ADAMTS13:AC高（>7.9）的患者与低（≤7.9）的患者相比，ACLF累积发病率显著更高（风险比[HR]，6.50；95%CI，2.31-18.29；P<0.001）。VWF:Ag/ADAMTS13:AC高的肝硬化患者与低的患者相比，累积生存率显著更低（HR 5.11；95%CI，1.85-14.14；P=0.002）。
对于肝硬化患者，VWF:Ag/ADAMTS13:AC与肝脏功能储备相关，并可预测ACLF的发生及预后。
