Incidence and risk factors for chronic rejection in pediatric liver transplantation

Chronic rejection (CR) is a progressive immunological injury that frequently leads to long-term liver allograft dysfunction and loss. Although CR remains an important indication for re-transplantation, as transplant immunosuppression has evolved, its prevalence in adults undergoing liver transplantation (LT) has declined. However, the incidence and factors that lead to CR in pediatric LT are poorly defined. Therefore, we sought to systematically measure CR's incidence and assess both the risk factors for developing CR and outcomes in a large cohort of pediatric LT recipients. In this single center study, we retrospectively analyzed and compared relevant recipient characteristics, surgical details, immunosuppression, graft, and patient survival in the CR and control groups over a 17-year period. After a median time of 1.9 years post-LT, 19/356 LT recipients (5.3%) developed CR in our cohort. Post-transplant lymphoproliferative disorder (p=0.01), infections (p=0.02), autoimmune liver diseases (HR 7.3, p=<0.01), Black race (HR11.5, p=0.01) and two or more episodes of acute cellular rejection (HR 5.1, p=<0.01) were associated with CR development. The re-transplantation rate among CR cases was 15.8% at a median follow-up time of 4.1 years. Overall, patient survival was lower in the CR group (78.9%) versus controls (91.1%). While CR incidence in our pediatric cohort was lower than previously reported rates of ˃12%, the CR group had a higher graft failure rate that required re-transplantation and lower overall patient survival. Thus, identifying risk factors may warrant specialized immunosuppression protocols and closer post-transplantation monitoring to reduce the risk of morbidity and mortality from CR.