CD105 CD146 circulating endothelial cells facilitate liver regeneration and predict posthepatectomy liver failure in humans

Question:

Insufficient regeneration after liver resection results in posthepatectomy liver failure (PHLF), which presents the main cause of mortality after hepatectomy. Even though angiogenesis is known to play a critical role, little is known about the role of its cellular and molecular factors in the context of human liver regeneration. It was therefore the aim of the present study to investigate a potential role of circulating endothelial cels (CEC) in liver regeneration and PHLF.

Methods:

A total of 115 undergoing liver resection for metastatic colorectal cancer were enrolled prospectively. Blood samples were collected prior to incision. In a subset (n = 39) additional blood samples were collected on postoperative day 3 (POD 3). CEC were quantified using the CellSearch System by certified staff and defined as CD146 CD105 DAPI CD45- events. The International Study Group of Liver Surgery (ISGLS) definition of PHLF was applied. For CEC, preoperative and POD 3 values were evaluated as well as their perioperative kinetics (i.e. Δ CEC). Cut-off values were determined using receiver operating characteristic (ROC) curve analyses. Univariate analyses were carried out using a paired t-test, Wilcoxon rank sum test and chi-square test. Logistic regression models were applied in multivariate analyses.

Results:

A major hepatectomy was performed in 39 (33.9%) patients. PHLF developed in 12 (10.4%) patients. The median preoperative CEC count in the entire cohort was 18 (9 – 37). There were no significant associations of clinicopathologic variables with preoperative CEC counts. Analyses of perioperative CEC kinetics revealed no significant changes after minor hepatectomies, whereas CEC on POD 3 were significantly increased compared to preoperative values after major hepatectomies (15.5 [13 – 24.25] vs. 52.5 [20.5 vs. 270.5]; p = 0.04). Except for the extent of hepatectomy (p = 0.006), no further clinicopathologic factors were associated with Δ CEC. Using cut-off values of 17, 52 and 27 per ROC curve analyses, preoperative CEC (p = 0.04), CEC on POD 3 (p = 0.004) and Δ CEC (p < 0.001) were associated with PHLF on univariate analyses. On separate multivariate analyses CEC on POD 3 (p = 0.02) and Δ CEC (p = 0.005) were confirmed as independent predictors of PHLF.

Conclusions:

CEC counts are increased postoperatively in patients undergoing major hepatectomy indicating a potential role in liver regeneration. The extent of postoperative CEC increase is and early and independent predictor of PHLF.