Schotters FL, Beime J, Briem-Richter A, Binder T, Herden U, Grabhorn EF. Impact of donor-specific antibodies on long-term graft survival with pediatric liver transplantation. World J Hepatol 2021; 13(6): 673-685 [PMID: 34239702 DOI: 10.4254/wjh.v13.i6.673]
Corresponding Author of This Article
Enke Freya Grabhorn, MD, Attending Doctor, Department of Pediatric Hepatology and Liver Transplantation, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, Hamburg 20246, Germany. e.grabhorn@uke.de
Research Domain of This Article
Transplantation
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Hepatol. Jun 27, 2021; 13(6): 673-685 Published online Jun 27, 2021. doi: 10.4254/wjh.v13.i6.673
Impact of donor-specific antibodies on long-term graft survival with pediatric liver transplantation
Felicitas Leonie Schotters, Jan Beime, Andrea Briem-Richter, Thomas Binder, Uta Herden, Enke Freya Grabhorn
Felicitas Leonie Schotters, Jan Beime, Andrea Briem-Richter, Enke Freya Grabhorn, Department of Pediatric Hepatology and Liver Transplantation, Universitätsklinikum Hamburg-Eppendorf, Hamburg 20246, Germany
Thomas Binder, Department of Transfusion Medicine, Human Leucocyte Antigen Laboratory, University Medicine Rostock, Rostock 18057, Germany
Uta Herden, Department of Hepatobiliary & Transplant Surgery, Universitätsklinikum Hamburg-Eppendorf, Hamburg 20246, Germany
Author contributions: Schotters FL participated in research design, performed the data collection, performed the research and data analysis, created figures and tables and wrote the paper; Beime J performed a critical revision and participated in writing the manuscript; Briem-Richter A participated in research design; Binder T performed a critical revision; Herden U performed a critical revision; Grabhorn E participated in research design, writing the manuscript, performance of the research and supervised the report.
Institutional review board statement: Our study was approved by the responsible ethics committee.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE statement, and the manuscript was prepared and revised according to the STROBE statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Enke Freya Grabhorn, MD, Attending Doctor, Department of Pediatric Hepatology and Liver Transplantation, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, Hamburg 20246, Germany. e.grabhorn@uke.de
Received: January 8, 2021 Peer-review started: January 8, 2021 First decision: March 29, 2021 Revised: April 12, 2021 Accepted: May 21, 2021 Article in press: May 21, 2021 Published online: June 27, 2021 Processing time: 148 Days and 4.6 Hours
Abstract
BACKGROUND
In a previous paper, we reported a high prevalence of donor-specific antibody (DSA) in pediatric patients with chronic rejection and expressed the need for confirmation of these findings in a larger cohort.
AIM
To clarify the importance of DSAs on long-term graft survival in a larger cohort of pediatric patients.
METHODS
We performed a retrospective analysis of 123 pediatric liver transplantation (LT) recipients who participated in yearly follow-ups including Luminex testing for DSA at our center. The cohort was split into two groups according to the DSA status (DSA-positive n = 54, DSA-negative n = 69). Groups were compared with regard to liver function, biopsy findings, graft survival, need for re-LT and immunosuppressive medication.
RESULTS
DSA-positive pediatric patients showed a higher prevalence of chronic rejection (P = 0.01), fibrosis (P < 0.001) and re-transplantation (P = 0.018) than DSA-negative patients. Class II DSAs particularly influenced graft survival. Alleles DQ2, DQ7, DQ8 and DQ9 might serve as indicators for the risk of chronic rejection and/or allograft fibrosis. Mean fluorescence intensity levels and DSA number did not impact graft survival. Previous episodes of chronic rejection might lead to DSA development.
CONCLUSION
DSA prevalence significantly affected long-term liver allograft performance and liver allograft survival in our cohort of pediatric LT. Screening for class II DSAs in combination with assessment of protocol liver biopsies for chronic antibody-mediated rejection improved early identification of patients at risk of graft loss.
Core Tip: This was a retrospective study to evaluate the impact of donor-specific antibodies (DSAs) on graft survival with pediatric liver transplantation. Graft fibrosis and graft loss was significantly higher in patients with DSAs. Screening for DSAs should be included in follow-ups to avoid delayed identification of patients at risk of graft loss (rejection), and may be even more relevant for patients with early histological signs of possible allograft dysfunction (fibrosis). Moreover, patients with DSAs may be poor candidates for reduction of initial immunosuppression or even weaning.
