Tissue inhibitor of metalloproteinase-2 predicts early allograft dysfunction after liver transplantation.

BACKGROUND: The lack of objective criteria to assess graft integrity represents a major impediment to the acceptance of livers of limited quality as a way to increase the donor pool in liver transplantation. Extracorporeal machine perfusion prior to transplantation may serve as a valuable platform to second to the surgeon's decision on acceptance or discard of the organ, but, to date, the availability of valuable perfusate biomarkers is rather poor. Tissue inhibitor of metalloproteinase-2 (TIMP2) is a protein actively secreted upon epithelial cell stress and involved in the suppression of endothelial cell proliferation. METHODS: A total of 20 livers grafts from extended criteria donors, which were shipped to the implantation clinic by conventional cold storage, were subjected to 90 min of ex vivo machine perfusion after arrival. At the end of liver perfusion, perfusate concentrations of TIMP2 were measured and related to the occurrence of early allograft dysfunction after transplantation. RESULTS: ROC analysis disclosed a significant (p = 0.0046; CI 0.9-0.1) predictive potential of TIMP2 with a sensitivity to predict EAD of 1.0 (CI 0.51-1.0) and a specificity of 0.94 (CI 0.72-1.0) at a cut-off value of 2106 pg/ml. CONCLUSIONS: Determination of TIMP2, which is possible to be performed as point-of-care measure, may thus become a useful adjunct on the way to better evaluate extended criteria donor livers.