Effluent levels of hyaluronic acid can predict ultimate graft outcome after clinical liver transplantation: a prospective series.

PRIMARY nonfunction (PNF) of the liver is an inexact term and investigators continue to debate the site and origin of preservation injury. Some grafts with PNF fail in the operating room. while other grafts have to be replaced between I and 14 days postoperatively. The pathology of such grafts displays a spectrum of findings ranging from marked hepatocellular swelling and cholestasis to massive ischemic necrosis. Both recipient and donor etiological factors potentially contribute to PNF. Donor factors include the physiological condition of the heart-beating cadaver before organ procurement. the methods of preservation. period of cold ischemia. and various reperfusion phenomena. To date. there has been no proven method to discriminate in advance of transplantation between clinically acceptable and unacceptable liver allografts. Because the critical target of preservation injury has been increasingly perceived to be the hepatocyte microvasculature (HMV). U we attempted in this study to correlate hyaluronic acid (HA), an HMV-specific mark-' er.J-~ with ultimate graft outcome. Hyaluronic acid is a glycosoaminoglycan weighing 4 to 8 million kd. It is synthesized in the cell plasma membrane. deposited in the extracellular matrix. transported by the lymphatics. and uniquely catabolized by the liver HMV. ,-~ Serum HA has been used to monitor liver graft function/> and as a prognostic marker after Tylenol poisoning. 7 Because HA is concentrated in HMV cells. the rationale for the present study was that preservation injury to these cells will result in the leakage of this substance into the organ effi!1ent. where it can be collected and assayed on the backtable before liver transplantation. I n a preliminary retrospective study. the feasibility was demonstrated of correlating effluent HA levels with graft function and viability in an accurate and reproducible manner. Effluent HA values of s400 I-Lg/L were associated with unequivocal early graft function. and grafts with HA values of >400 I-Lg/L were at high risk of developing PNF. ~ Therefore, we undertook the following prospective study.