Late Graft Hepatitis and Fibrosis in Pediatric Liver Allograft Recipients: Current Concepts and Future Developments

Liver transplantation (LT) in children now has a 20-year survival of >80%, but the longterm outcome of these grafts remains uncertain. Serial protocol liver biopsies after transplantation from several pediatric centres have demonstrated the gradual development of unexplained graft inflammation ("idiopathic" posttransplant hepatitis; IPTH) and graft fibrosis in biopsies obtained >12 months post-LT in children with good graft function and (near) normal liver biochemistry. Although the clinical significance of these findings is uncertain, there is evidence to suggest that IPTH may be a form of rejection or chronic antibody-mediated rejection as it is associated with the presence of auto/alloantibodies; de novo Class II donor-specific HLA antibodies (DSA); previous episodes of rejection, and may improve or be prevented with increased immunosuppression. Currently, the only method of diagnosing either hepatitis or fibrosis has been by serial protocol biopsies as neither serum markers of fibrosis nor noninvasive methods to detect fibrosis such as transient elastography (TE) are sufficiently validated in children. This review will focus on the diagnosis and management of idiopathic posttransplant hepatitis and graft fibrosis, discuss current methods for detecting graft injury, and potential mechanisms for their development.