Fibrosis in the Time Zero Liver Allograft Biopsy Predicts Decreased Long Term Graft Survival: Implications for Liver Allograft Allocation and Mechanisms of Failure
Ellen Fraint, Anthony Guzman, Peter Abt, Emma Elizabeth Furth. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Background: Time zero liver allograft biopsies are routinely performed at the time of liver transplantation. We have previously shown that several features in these biopsies are predictive of outcomes within the first three months (Human Pathology 27(10):1077-1084, 1996). The goal of this study was to determine which features in the time zero biopsy were predictive of long term outcomes.
Design: From 545 adult patients undergoing liver transplantation between 2005-2010 at our institution, 101 patients were randomly selected for re-review of their time zero liver biopsies for % macrovesicular steatosis, fibrosis (0[none], 0.5[minimal], 1[moderate portal expansion], 2[septate], 3[bridging], 4[cirrhosis]; trichrome stain), inflammation (0-3), apoptotic and mitotic indices, and hepatocyte swelling. Kaplan Meier survival curves were constructed for each variable at 3 months, 1 year, and 3 years, with the endpoint “graft survival” defined as patient death or re-transplantation. We also compared the slide re-reviews with the original time zero pathology report.
Results: Only the feature of fibrosis significantly predicted reduced survival, from 87.5% to 63.6% (p=.044) at 3 years post transplantation. Patients with at most "mild" fibrosis had a mean survival of 110 days longer than those grafts with more significant fibrosis. Our cohort consisted of 83% men and 17% women with median age 53 years (19-73), 50% of whom were transplanted for cirrhosis due to hepatitis C. The median cold ischemic time of 5.3 hours is short compared to UNOS of 8.2. Our cohort composition for fibrosis was 0 = 85%, minimal = 2%, 1 = 10%, and 2 = 1%. For steatosis, 84% had < 10%, 12% had 10-30%, and 4% had > 30%. Compared to the original pathology report, the re-review of the % steatosis and degree of fibrosis did not significantly differ.
Conclusions: That pre-existent fibrosis predicts decreased long term survival post liver transplantation may have implications in the method and criteria for evaluating and deciding on the use of livers for engraftment. As well, our results imply that fibrogenic processes already set in motion prior to liver engraftment have long term biologic effects.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 261, Monday Morning