title: Late graft hepatitis and fibrosis in pediatric liver allograft recipients: Current concepts and future developments.
abstract: 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. Liver Transplantation 22 1593-1602 2016 AASLD.
authors.affiliation: Liver Unit, Birmingham Children's Hospital and University of Birmingham, Birmingham, United Kingdom. deirdre.kelly@bch.nhs.uk.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Kelly
authors.affiliation: Department of Pediatrics, Beatrix Children's Hospital/University Medical Center, Groningen University, Groningen, the Netherlands.
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Verkade
authors.affiliation: Royal Children's Hospital, Melbourne, Australia.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Rajanayagam
authors.affiliation: Liver Unit, Birmingham Children's Hospital and University of Birmingham, Birmingham, United Kingdom.
authors.forename: Patrick
authors.initials: P
authors.lastname: McKiernan
authors.affiliation: Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh, Pittsburgh, PA.
authors.forename: George
authors.initials: G
authors.lastname: Mazariegos
authors.affiliation: Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.|Department of Cellular Pathology, University Hospitals Birmingham, National Health Service Foundation Trust, Birmingham, United Kingdom.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hübscher
mesh_terms: D064591:Allografts / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002648:Child; D054459:Elasticity Imaging Techniques / Q000379:methods*; D005355:Fibrosis; D006084:Graft Rejection / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology; D006505:Hepatitis / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D007165:Immunosuppression Therapy; D015994:Incidence; D007518:Isoantibodies / Q000276:immunology; D008099:Liver / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects*; D014184:Transplantation, Homologous / Q000009:adverse effects
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D006680:HLA Antigens; D007518:Isoantibodies