Anthony J Demetris1, Adriana Zeevi, Jacqueline G O'Leary. 1. 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.
Abstract
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
Authors: Thomas E Starzl; Anthony J Demetris; Satoru Todo; Yoogoo Kang; Andreas Tzakis; Rene Duquesnoy; Leonard Makowka; Barbara Banner; Waldo Concepcion; Kendrick A Porter Journal: Clin Transplant Date: 1989 Impact factor: 2.863
Authors: Anthony J Demetris; John G Lunz; Parmjeet Randhawa; Tong Wu; Michael Nalesnik; Angus W Thomson Journal: Transpl Int Date: 2008-09-26 Impact factor: 3.782
Authors: S L Saidman; R J Duquesnoy; A J Demetris; J McCauley; H Ramos; G Mazariegos; R Shapiro; T E Starzl; J J Fung Journal: Transpl Immunol Date: 1994 Impact factor: 1.708
Authors: Anya Adair; David R Mitchell; Tiina Kipari; Feng Qi; Christopher O C Bellamy; Faye Robertson; Jeremy Hughes; Lorna P Marson Journal: Transplantation Date: 2007-06-27 Impact factor: 4.939
Authors: Sandy Feng; Anthony J Demetris; Katharine M Spain; Sai Kanaparthi; Bryna E Burrell; Udeme D Ekong; Estella M Alonso; Philip Rosenthal; Laurence A Turka; David Ikle; Nadia K Tchao Journal: Hepatology Date: 2016-07-27 Impact factor: 17.425