Protocol biopsies in pediatric liver transplantation recipients improve graft histology and personalize immunosuppression

Objectives: Protocol liver biopsies (PLB) are part of the follow-up program at many pediatric liver transplant centers, but the impact on clinical decision-making and allograft histology following adjustments of immunosuppression (IS) after PLB has not been thoroughly analyzed. Methods: Following our previous single-center cohort study, we have now evaluated histological findings of 178 PLPs of 118 pediatric patients transplanted at our center between 1998 and 2017. In particular, we focused on the changes in allograft histology in the follow-up biopsy of a subgroup of 22 patients, in which the histologic findings led to an adjustment of immunosuppressive therapy. All biopsies of this sub-study group were re-evaluated by an experienced pathologist. Results: The overall frequency and severity of fibrosis increased over time after orthotopic liver transplantation. Patients with donor-specific antibodies (DSAs) had a higher prevalence of fibrosis than DSA-negative patients. Graft inflammation decreased significantly after intensifying IS, but potential renal function needs to be monitored. A significant increase in fibrosis was detected in children with reduced IS. Conclusion: The adjustment of IS following PLBs has a significant impact on allograft histology. Since chronic inflammatory changes may lead to graft failure, adjustment of IS seems to be of major importance for the long-term outcome.