Banff Liver Allograft Pathology Group: late rejection activity is insufficiently represented in the current diagnostic framework - rationale and goals for revision.

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.