Christopher Bellamy, Claudia Mescoli, Khashayar Asadi, Oyedele A Adeyi, Rachel M Brown, Lindsey Clarke, Zeynep Demir, Sadhna Dhingra, Michail Doukas, Mohamad El Hag, Bastian Engel, Sandy Feng, Maria I Fiel, Alessandro Gambella, Krzyztof Grzyb, Horonori Haga, Laura Heij, Elmar Jaekel, Anthea Lafreniere, Jan P Lerut, Andrew Lesniak, Geoffrey W McCaughan, Catriona McKenzie, Rosa Miquel, Charlotte Mussini, Deslie Neil, Anna L Paterson, Avandi A Pendse, Henrik M Reims, Olorunda Rotimi, Alberto Sanchez Fueyo, Thomas D Schiano, Mylene Sebagh, Maxwell Smith, Heather L Stevenson, Timucin Taner, Ryan Y Tanigawa, Richard Taubert, Elena Y Uebayashi, Funda Yilmaz, Jacqueline G O'Leary, Anthony J Demetris
Late liver allograft rejection is under-recognized because it is often clinically silent, liver tests are insensitive, protocol biopsies are uncommon, and the histology differs from classic early acute T cell-mediated rejection (TCMR) manifesting in the initial weeks after transplantation. Differences in tempo and pathogenesis lead to distinct clinical and histologic manifestations. Late- compared with acute-TCMR is characterized by more prevalent interface and perivenular inflammatory activity, a lymphocyte-predominant infiltrate and fibrosis, with less conspicuous portal duct-centered and subendothelial venular inflammation. The traditional Banff RAI scheme that works consistently well to diagnose acute-TCMR is less well calibrated to account for these later shifts of inflammatory target and density, risking under-diagnosis of clinically significant late-TCMR. This document lays out the histopathologic characteristics of acute- vs. late-TCMR and the rationale for updating the Banff scoring system for liver allograft rejection to better incorporate currently unrepresented histology features correlating with a molecular rejection signature into the Banff rejection scheme.