HYALURONATE LEVELS IN DONOR ORGAN WASHOUT EFFLUENTS - A SIMPLE AND PREDICTIVE PARAMETER OF GRAFT VIABILITY

The principal cause of primary non-function in orthotopic liver transp lantation is thought to be preservation injury to the microvasculature . We, therefore, evaluated if effluent levels of hyaluronate, whose up take is an endothelial cell marker, could predict early graft function and ultimate graft outcome in orthotopic liver transplantation. A tot al of 102 cases were studied in two phases. In the first phase, we att empted to determine if a correlation existed between effluent hyaluron ate levels, early graft function and ultimate graft outcome. This phas e of the study was also used to determine hypothetical cut-off values for hyaluronate which could discriminate between good and bad livers. Thirty-two livers orthotopically transplanted to randomly selected pri mary recipients were studied. After varying periods of static cold sto rage (4 degrees C) in University of Wisconsin solution, the livers wer e reinfused with cold (4 degrees C) lactated Ringer's solution. The fi rst 50 ml of the reperfusion effluent was collected from the infrahepa tic vena cava. Effluent samples were analyzed for hyaluronate, Linear regression analysis demonstrated a significant correlation between eff luent hyaluronate levels and post-operative aspartate and alanine amin otransferase levels (p<0.001 for both). Logistic regression demonstrat ed a highly significant correlation (p=0.0056) between effluent hyalur onate levels and ultimate graft outcome, Generation of Receiver Charac teristics Curves indicated that a level between 400 and 430 mu g . l(- 1) could possibly discriminate between good livers and those at risk o f early graft failure. The authenticity of this hyaluronate cut-off le vel was further confirmed in the second phase of the study where 70 co nsecutive primary crossmatch-negative transplants were performed. A hi ghly significant difference was observed in peak aspartate and alanine aminotransferase levels in the first week (p<0.0006 and p<0.0005, res pectively) between livers with effluent hyaluronate levels less than o r equal to 400 mu g . l(-1) and livers with hyaluronate levels higher than 400 mu g . l(-1). Logistic regression revealed a highly significa nt correlation between effluent hyaluronate levels and graft success ( p=0.0001). Since hyaluronate uptake by the microvascular endothelial c ell is significantly greater than production, high hyaluronate effluen t levels in failed livers would be due to decreased hyaluronate uptake by the injured microvascular endothelial cell, We therefore conclude that effluent hyaluronate levels may prove to be a reliable preoperati ve test to assess early graft function and outcome in clinical orthoto pic liver transplantation.