Thomsen Karen L, Robertson Francis P, Holland-Fischer Peter, Davidson Brian R, Mookerjee Rajeshwar P, Møller Holger J, Jalan Rajiv, Grønbæk Henning
Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
Liver Failure Group, UCL Institute for Liver and Digestive Health, University College London, United Kingdom.
J Clin Exp Hepatol. 2019 May-Jun;9(3):302-311. doi: 10.1016/j.jceh.2018.09.006. Epub 2018 Oct 5.
BACKGROUND/OBJECTIVES: Soluble CD163 (sCD163), a macrophage activation marker, is upregulated in conditions of macrophage proliferation and activation. Elevated sCD163 levels have been associated with liver disease severity and progression. During liver transplantation, the implanted liver is exposed to ischaemia and reperfusion injury, resulting in an acute inflammatory response and macrophage activation. The relationship between sCD163 levels during liver transplantation and the development of early allograft dysfunction (EAD) has not been investigated.
We included 27 cirrhosis patients (age 55 [range 32-72] years, 23 men) on the waiting list for liver transplantation. Alcohol consumption and viral hepatitis were the most frequent causes for cirrhosis. Patients were characterised by standard biochemical analysis and based on clinical disease severity scores. Information about donor, graft and course of the liver transplantation was recorded. sCD163 levels were measured at the time of liver transplantation before surgery, 2 h after reperfusion, and then at 24 h after transplantation.
We observed above-normal sCD163 levels at baseline (5.9 mg/L [4.7-8.8]). Two hours after reperfusion, sCD163 levels increased significantly from baseline (8.4 mg/L [7.4-10.9]; < 0.01). Twenty-four hours after transplantation, sCD163 levels were significantly reduced compared with baseline (3.7 mg/L [2.9-5.5]; < 0.01). However, in patients with EAD (n = 16), sCD163 levels were increased compared with patients without EAD (4.1 [3.2-7.4] vs. 3.1 [2.8-3.8] mg/L; = 0.03).
We observed elevated sCD163 levels in patients with EAD after liver transplantation, confirming macrophage activation to play a role in EAD. Thus, sCD163 may be used as an early marker for EAD after liver transplantation, but larger studies are warranted to validate these findings.
背景/目的:可溶性CD163(sCD163)是一种巨噬细胞活化标志物,在巨噬细胞增殖和活化的情况下会上调。sCD163水平升高与肝脏疾病的严重程度和进展相关。在肝移植过程中,植入的肝脏会遭受缺血再灌注损伤,导致急性炎症反应和巨噬细胞活化。肝移植期间sCD163水平与早期移植物功能障碍(EAD)发生之间的关系尚未得到研究。
我们纳入了27名等待肝移植的肝硬化患者(年龄55岁[范围32 - 72岁],23名男性)。酒精性肝病和病毒性肝炎是肝硬化最常见的病因。通过标准生化分析并基于临床疾病严重程度评分对患者进行特征描述。记录有关供体、移植物和肝移植过程的信息。在肝移植手术前、再灌注后2小时以及移植后24小时测量sCD163水平。
我们观察到基线时sCD163水平高于正常(5.9mg/L[4.7 - 8.8])。再灌注后2小时,sCD163水平较基线显著升高(8.4mg/L[7.4 - 10.9];P<0.01)。移植后24小时,sCD163水平较基线显著降低(3.7mg/L[2.9 - 5.5];P<0.01)。然而,在发生EAD的患者(n = 16)中,与未发生EAD的患者相比,sCD163水平升高(4.1[3.2 - 7.4] vs. 3.1[2.8 - 3.8]mg/L;P = 0.03)。
我们观察到肝移植后发生EAD的患者sCD163水平升高,证实巨噬细胞活化在EAD中起作用。因此,sCD163可能用作肝移植后EAD的早期标志物,但需要更大规模的研究来验证这些发现。