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The New Challenge in Pediatric Liver Transplantation: Chronic Antibody-Mediated Rejection

Antibody-mediated rejection (AMR) of liver allograft transplantation was considered as anecdotal for many decades. However recently, AMR has gained clinical awareness as a potential cause of chronic liver injury, leading to liver allograft fibrosis and eventual graft failure. (1) Methods: Literature...

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Autores principales: Uebayashi, Elena Yukie, Okajima, Hideaki, Yamamoto, Miki, Ogawa, Eri, Okamoto, Tatsuya, Haga, Hironori, Hatano, Etsurou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409831/
https://www.ncbi.nlm.nih.gov/pubmed/36013073
http://dx.doi.org/10.3390/jcm11164834
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author Uebayashi, Elena Yukie
Okajima, Hideaki
Yamamoto, Miki
Ogawa, Eri
Okamoto, Tatsuya
Haga, Hironori
Hatano, Etsurou
author_facet Uebayashi, Elena Yukie
Okajima, Hideaki
Yamamoto, Miki
Ogawa, Eri
Okamoto, Tatsuya
Haga, Hironori
Hatano, Etsurou
author_sort Uebayashi, Elena Yukie
collection PubMed
description Antibody-mediated rejection (AMR) of liver allograft transplantation was considered as anecdotal for many decades. However recently, AMR has gained clinical awareness as a potential cause of chronic liver injury, leading to liver allograft fibrosis and eventual graft failure. (1) Methods: Literature on chronic AMR (cAMR) in pediatric post-liver transplant patients was reviewed for epidemiologic data, physiopathology, diagnosis, and treatment approaches. (2) Results: Accurate incidence of cAMR in pediatric liver transplantation remains unknown. Diagnostic criteria of cAMR were suggested by the Banff Working Group in 2016 and are based on standardized histopathological findings, C4d staining pattern, associated with the presence of donor-specific antibodies (DSA). Physio-pathological mechanisms are not clear for the technically difficult-to-obtain animal models reproducing cAMR. Treatment protocols are not established, being limited to case reports and case series, based on experience in ABO incompatible transplantation and kidney transplantation. Immunosuppression compliance with adequate dose adjustment may prevent cAMR. Conversion of Cyclosporine to Tacrolimus may improve pathological findings if treated in early phase. The association of steroids, Mycophenolate Mofetil (MMF) and mTOR inhibitors have shown some synergistic effects. Second-line treatments such as intravenous immunoglobulin (IVIG) and plasma exchange may decrease antibody titers based on ABO incompatible transplant protocols. The use of anti-CD20 (Rituximab) and proteasome inhibitors (Bortezomib) is controversial due to the lack of qualified studies. Therefore, multicenter randomized trials are needed to establish the best therapeutic strategy. In refractory cases, re-transplantation is the only treatment for allograft failure. (3) Conclusions: This literature review collects recent clinical, histopathological, and therapeutical advances of cAMR in liver allograft transplantation of pediatric patients. There are many physio-pathological aspects of cAMR to be clarified. Further efforts with multicenter prospective protocols to manage patients with cAMR are needed to improve its outcome.
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spelling pubmed-94098312022-08-26 The New Challenge in Pediatric Liver Transplantation: Chronic Antibody-Mediated Rejection Uebayashi, Elena Yukie Okajima, Hideaki Yamamoto, Miki Ogawa, Eri Okamoto, Tatsuya Haga, Hironori Hatano, Etsurou J Clin Med Review Antibody-mediated rejection (AMR) of liver allograft transplantation was considered as anecdotal for many decades. However recently, AMR has gained clinical awareness as a potential cause of chronic liver injury, leading to liver allograft fibrosis and eventual graft failure. (1) Methods: Literature on chronic AMR (cAMR) in pediatric post-liver transplant patients was reviewed for epidemiologic data, physiopathology, diagnosis, and treatment approaches. (2) Results: Accurate incidence of cAMR in pediatric liver transplantation remains unknown. Diagnostic criteria of cAMR were suggested by the Banff Working Group in 2016 and are based on standardized histopathological findings, C4d staining pattern, associated with the presence of donor-specific antibodies (DSA). Physio-pathological mechanisms are not clear for the technically difficult-to-obtain animal models reproducing cAMR. Treatment protocols are not established, being limited to case reports and case series, based on experience in ABO incompatible transplantation and kidney transplantation. Immunosuppression compliance with adequate dose adjustment may prevent cAMR. Conversion of Cyclosporine to Tacrolimus may improve pathological findings if treated in early phase. The association of steroids, Mycophenolate Mofetil (MMF) and mTOR inhibitors have shown some synergistic effects. Second-line treatments such as intravenous immunoglobulin (IVIG) and plasma exchange may decrease antibody titers based on ABO incompatible transplant protocols. The use of anti-CD20 (Rituximab) and proteasome inhibitors (Bortezomib) is controversial due to the lack of qualified studies. Therefore, multicenter randomized trials are needed to establish the best therapeutic strategy. In refractory cases, re-transplantation is the only treatment for allograft failure. (3) Conclusions: This literature review collects recent clinical, histopathological, and therapeutical advances of cAMR in liver allograft transplantation of pediatric patients. There are many physio-pathological aspects of cAMR to be clarified. Further efforts with multicenter prospective protocols to manage patients with cAMR are needed to improve its outcome. MDPI 2022-08-18 /pmc/articles/PMC9409831/ /pubmed/36013073 http://dx.doi.org/10.3390/jcm11164834 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Uebayashi, Elena Yukie
Okajima, Hideaki
Yamamoto, Miki
Ogawa, Eri
Okamoto, Tatsuya
Haga, Hironori
Hatano, Etsurou
The New Challenge in Pediatric Liver Transplantation: Chronic Antibody-Mediated Rejection
title The New Challenge in Pediatric Liver Transplantation: Chronic Antibody-Mediated Rejection
title_full The New Challenge in Pediatric Liver Transplantation: Chronic Antibody-Mediated Rejection
title_fullStr The New Challenge in Pediatric Liver Transplantation: Chronic Antibody-Mediated Rejection
title_full_unstemmed The New Challenge in Pediatric Liver Transplantation: Chronic Antibody-Mediated Rejection
title_short The New Challenge in Pediatric Liver Transplantation: Chronic Antibody-Mediated Rejection
title_sort new challenge in pediatric liver transplantation: chronic antibody-mediated rejection
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409831/
https://www.ncbi.nlm.nih.gov/pubmed/36013073
http://dx.doi.org/10.3390/jcm11164834
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