ABO-compatible liver allograft antibody-mediated rejection: an update. 2015

Anthony J Demetris, and Adriana Zeevi, and Jacqueline G O'Leary
aDivision of Transplantation, Department of Pathology, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania bAnnette C. & Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas, USA.

OBJECTIVE Liver allograft antibody-mediated rejection (AMR) studies have lagged behind parallel efforts in kidney and heart because of a comparative inherent hepatic resistance to AMR. Three developments, however, have increased interest: first, solid phase antibody testing enabled more precise antibody characterization; second, increased expectations for long-term, morbidity-free survival; and third, immunosuppression minimization trials. RESULTS Two overlapping liver allograft AMR phenotypic expressions are beginning to emerge: acute and chronic AMR. Acute AMR usually occurs within the several weeks after transplantation and characterized clinically by donor-specific antibodies (DSA) persistence, allograft dysfunction, thrombocytopenia, and hypocomplementemia. Acute AMR appears histopathologically similar to acute AMR in other organs: diffuse microvascular endothelial cell hypertrophy, C4d deposits, neutrophilic, eosinophilic, and macrophag-mediated microvasculitis/capillaritis, along with liver-specific ductular reaction, centrilobular hepatocyte swelling, and hepatocanalicular cholestasis often combined with T-cell-mediated rejection (TCMR). Chronic AMR is less well defined, but strongly linked to serum class II DSA and associated with late-onset acute TCMR, fibrosis, chronic rejection, and decreased survival. Unlike acute AMR, chronic AMR is a slowly evolving insult with a number of potential manifestations, but most commonly appears as low-grade lymphoplasmacytic portal and perivenular inflammation accompanied by unusual fibrosis patterns and variable microvascular C4d deposition; capillaritis can be more difficult to identify than in acute AMR. CONCLUSIONS More precise DSA characterization, increasing expectations for long-term survival, and immunosuppression weaning precipitated a re-emergence of liver allograft AMR interest. Pathophysiological similarities exist between heart, kidney, and liver allografts, but liver-specific considerations may prove critical to our ultimate understanding of all solid organ AMR.

UI MeSH Term Description Entries
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D006084 Graft Rejection An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. Transplant Rejection,Rejection, Transplant,Transplantation Rejection,Graft Rejections,Rejection, Graft,Rejection, Transplantation,Rejections, Graft,Rejections, Transplant,Rejections, Transplantation,Transplant Rejections,Transplantation Rejections
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000017 ABO Blood-Group System The major human blood type system which depends on the presence or absence of two antigens A and B. Type O occurs when neither A nor B is present and AB when both are present. A and B are genetic factors that determine the presence of enzymes for the synthesis of certain glycoproteins mainly in the red cell membrane. ABH Blood Group,ABO Blood Group,ABO Factors,Blood Group H Type 1 Antigen,H Blood Group,H Blood Group System,ABO Blood Group System,Blood Group, ABH,Blood Group, ABO,Blood Group, H,Blood-Group System, ABO,Factors, ABO,System, ABO Blood-Group
D014184 Transplantation, Homologous Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals. Transplantation, Allogeneic,Allogeneic Grafting,Allogeneic Transplantation,Allografting,Homografting,Homologous Transplantation,Grafting, Allogeneic
D016031 Liver Transplantation The transference of a part of or an entire liver from one human or animal to another. Grafting, Liver,Hepatic Transplantation,Liver Transplant,Transplantation, Hepatic,Transplantation, Liver,Hepatic Transplantations,Liver Grafting,Liver Transplantations,Liver Transplants,Transplant, Liver
D064591 Allografts Tissues, cells, or organs transplanted between genetically different individuals of the same species. Allogeneic Grafts,Allogeneic Transplants,Homografts,Homologous Transplants,Allogeneic Graft,Allogeneic Transplant,Allograft,Graft, Allogeneic,Grafts, Allogeneic,Homograft,Homologous Transplant,Transplant, Allogeneic,Transplant, Homologous,Transplants, Allogeneic,Transplants, Homologous

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