Quantitative evaluation of histological features in "time-zero" liver allograft biopsies as predictors of rejection or graft failure: receiver-operating characteristic analysis application

Abstract

Harvest injury in liver transplantation adversely affects both allograft function and subsequent acute rejection. The aim of this study was to use receiver-operating characteristic (ROC) analysis to determine the strength of histological features in time-zero liver allograft biopsies as predictors of subsequent acute rejection episodes or primary allograft failure. The study population consisted of 38 patients who underwent orthotopic liver transplantation between 1989 and 1992. Time-zero biopsies and all subsequent biopsies were retrospectively reviewed. The following time-zero histological features were graded: hepatocyte swelling, centrilobular necrosis, centrilobular hemorrhage, neutrophilic infiltrate, cholestasis, and number of apoptotic cells. Eleven transplants showed primary graft nonfunction; 15 experienced one or more episodes of moderate to severe acute rejection; 4 experienced only mild rejection episodes; and 8 showed no rejection over long follow-up periods. ROC analysis showed that the presence of hepatocyte swelling in the time-zero biopsy is a significant predictor of subsequent moderate to severe rejection. Apoptotic cells, centrilobular hemorrhage, hepatocyte swelling, and centrilobular necrosis were all significant predictors of primary graft failure. No histological feature was predictive of subsequent mild rejection. In conclusion, certain histological features serve as markers for adverse outcomes in the liver transplant population. Patients who show apoptotic cells, centrilobular hemorrhage and necrosis, or hepatocyte swelling in their time-zero biopsy should be monitored carefully for signs of graft failure and rejection.