333.10: The Role of Immunosuppression Level in Liver Allograft Fibrosis After Pediatric Liver Transplantation

Abstract

Objective: Liver allograft fibrosis (LAF) is prevalent among patients with long-term survival after liver transplantation (LT). We aimed to identify clinical risk factors associated with LAF in pediatric LT recipients, with a focus on the impact of immunosuppression level on LAF and its evolution. Methods: A retrospective study on pediatric LT recipients with at least one-year follow up who underwent liver biopsy was conducted. Cox regression models were used to analyze risk factors associated with LAF, and landmark analysis was used to evaluate the impact of tacrolimus (TAC) level on LAF. Longitudinal analysis was also conducted in patients undergoing repeat liver biopsies. Results: A total of 139 patients involving 174 liver biopsies were included. With a 2.3-year follow-up period, LAF was detected in 91.4% of patients (9.4% had severe LAF). Episodes of acute rejection, biliary complications, positive cytomegalovirus DNA after LT, and prolonged cold ischemia time were independent risk factors for LAF. The risk in the low TAC level group at 1-3, 3-6, 6-12 and 12-36 months after LT was higher than the counterparts. Especially, in patients with high TAC level (≥ 5.1 ng/mL) during postoperative 1-3 years, the risk of LAF was 67% lower in the short-term (P = 0.006). Twenty-six patients underwent repeat biopsies. Patients with increasing TAC level after the first biopsy were more likely to achieve fibrosis reduction (HR = 7.53, P = 0.025). Conclusion: LAF is common among pediatric LT recipients with more than one-year of follow-up, but was mostly mild or moderate. Under-immunosuppression may contribute to the development of fibrosis; and the degree of LAF may be improved by administering adequate levels of immunosuppression.