Clinicopathologic Characteristic of Centrilobular Injury in Pediatric Liver Transplant.

Centrilobular injury (CLI) is defined as the presence of a perivenular mononuclear inflammation, drop-out of hepatocytes, and erythrocyte extravasates. In the pediatric liver allografts, CLI has been associated with advanced fibrosis and chronic rejection (CR). We sought to better characterize the clinicopathologic features of CLI in the setting of T-cell mediated rejection (TCR), and its association with C4d deposition. 206 post-transplant pediatric patients (491 allograft liver biopsies) were available from 2000-18 of which 63 patients (102 biopsies) show evidence of TCR and were included in the study. 35 patients (55.6%) had CLI upon their initial episode of TCR; those cases with CLI were significantly associated with the type of immunosuppression treatment (p=0.0296), severity of TCR (p<0.0001), higher gamma glutamyltransferase (GGT) (p=0.0136), and advanced fibrosis (p=0.0333). There was a trend to shorter time interval from transplantation to presentation of CLI compared to those without CLI (p=0.0578). No difference was observed in graft or overall survival in patient with CLI. In 20 patients with CLI additional biopsies were available, in 45% of patients CLI is a persistent/recurrent finding. C4d deposition was noted in 12% of all the biopsies (6 patients) with CLI. No significant correlation was noted in C4d deposition and CLI, CR, and graft/overall survival. In conclusion CLI, although not significantly associated with worse graft survival, was significantly associated with severe TCR and degree of fibrosis, which highlights the importance of active clinical management and follow-up for these patients.