The Macrophage Activation Marker Soluble CD163 is Associated With Early Allograft Dysfunction After Liver Transplantation

J Clin Exp Hepatol. 2019 May-Jun;9(3):302-311. doi: 10.1016/j.jceh.2018.09.006. Epub 2018 Oct 5.

Abstract

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.

Methods: 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.

Results: 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]; P < 0.01). Twenty-four hours after transplantation, sCD163 levels were significantly reduced compared with baseline (3.7 mg/L [2.9-5.5]; P < 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; P = 0.03).

Conclusions: 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.

Keywords: ALK, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CIT, cold ischaemic time; CRP, C-reactive protein; DBD, deceased brain death; DCD, deceased cardiac death; EAD, Early allograft dysfunction; ELISA, enzyme-linked immunosorbent assay; Hb, haemoglobin; I/R, ischaemia/reperfusion; IL, interleukin; INR, international normalised ratio; IQR, interquartile range; MELD, Model for End-Stage Liver Disease; NAFLD, nonalcoholic fatty liver disease; NF-κB, nuclear factor- κB; PT, prothrombin time; TNF-α, tumour necrosis factor α; WBC, white blood cell; WIT, warm ischaemic time; graft dysfunction; liver transplantation; macrophages; sCD163; sCD163, soluble CD163.