Impact of donor-specific antibodies on long-term graft survival with pediatric liver transplantation

doi:10.4254/wjh.v13.i6.673

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World Journal of Hepatology

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Retrospective Cohort Study

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.

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.

Keywords: Donor-specific antibodies; Graft rejection; Liver transplantation; Fluoroimmunoassay; Pediatrics; Graft dysfunction; Fibrosis

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.