Complement activation after ischemia-reperfusion in human liver allografts: Incidence and pathophysiological relevance

Background and Aims: Little is known about the occurrence and possible consequences of local complement activation in human liver transplantation. The aim of this study was to search for signs of complement activation in human liver allografts and evaluate their relationship to cell injury and leukocyte sequestration. Methods: In 33 postreperfusion biopsy specimens, 9 preoperative specimens, and 10 intraoperative specimens, the cytolytic membrane attack complex of complement was localized, expression of complement inhibitors was evaluated, and intragraft accumulation of leukocytes and platelets was quantitated. Results: In control samples and preoperative biopsy specimens, the membrane attack complex was detected only in extracellular deposits, associated with its soluble inhibitors clusterin and vitronectin. Comparable observations were performed in 14 postoperative specimens. In the remaining 19 postoperative specimens, membrane attack complex decorated a variable proportion of hepatocytes. The extent of membrane attack complex deposition correlated with the increase in postoperative aspartate aminotransferase levels in serum (P = 0.002) and the decrease in postoperative factor V levels in serum (P = 0.002). It also correlated with the number of leukocytes and platelets accumulating within the graft (P ≤ 0.001). Conclusions: Local complement activation is frequent during human liver transplantation and probably contributes to cell injury and leukocyte sequestration in the allograft.