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Development of DSA Class II is Associated with Immunosuppressive Monotherapy and Increased Risk for Graft Fibrosis, Chronic Rejection and Graft Loss

M. Sterneck1, B. Sultani1, A. Ozga2, S. Weidemann3, J. Hermann4, E. Grabhorn5, U. Herden6, L. Fischer6

1University Medical Center Hamburg Eppendorf, Hamburg, Germany, 2Insitute of Medical Biometry, University Medical Center Hamburg Eppendorf, Hamburg, Germany, 3Pathology, University Medical Center Hamburg Eppendorf, Hamburg, Germany, 4Pediatric Radiology, University Medical Center Hamburg Eppendorf, Hamburg, Germany, 5Pediatric Medicine, University Medical Center Hamburg Eppendorf, Hamburg, Germany, 6Transplant Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany

Meeting: 2020 American Transplant Congress

Abstract number: 153

Keywords: Antibodies, Fibrosis, Immunosuppression, Rejection

Session Information

Session Name: Liver: Immunosuppression and Rejection

Session Type: Oral Abstract Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:45pm

 Presentation Time: 3:39pm-3:51pm

Location: Virtual

*Purpose: Recent studies have suggested a negative impact of class 2 DSA on short term outcome of OLT recipients. The aim of this study was to assess the long-term risk for development of de novo DSA class 2 and their association with graft outcome.

*Methods: In this retrospective study all adult and pediatric OLT recipients with a 10-21 years post op follow-up presenting to the outpatient clinic of our institution between 2013 and 2019 were included. Patients with HCV infection were excluded. Graft fibrosis was assessed by liver elastography and biopsy. C4d stainings were retrospectively done. DSA class II were determined by Luminex technique and regarded as positive in case of a MFI > 1500 U.

*Results: Altogether 156 patients with a median follow-up of 15 years post OLT were analyzed. DSA Class 2 were positive (DSA+) in 72/156 (46%) patients. There was a significant increase in the prevalence of DSA class II from 17 % to 67% between the 10th and 21st year post OLT (p=0.042). In the multivariate analysis treatment with an immunosuppressive monotherapy (OR 5.4; p=0.048), time of follow-up (OR 1.4; p=0.04) and recipient’s age (OR 0.95; p=0.005) were risk factors for DSA development. There was no difference between DSA+ and DSA- patients with regard to early or late acute rejection episodes and biliary complications. But there was a significant shift towards higher fibrosis stages in DSA+ patients based on transient elastography (p=0.016) and histology results (p=0.016). Also, mean liver stiffness was significantly higher in DSA+ compared to DSA- patients (9.4 ± 9.0 kPa vs 6.5 ± 6.3 kPa; p<0.002). In the multivariate binary regression analysis DSA+ (OR 5.2; p=0.003) and immunosuppressive monotherapy (OR 3.3; p=0.06) were risk factors for fibrosis development. Also a significant higher incidence of chronic rejections (11% vs 2%; p=0.045) and graft losses (6% vs 0%; p=0.043) were found in DSA+ as compared to DSA- patients. All patients with graft loss during the observation period were DSA+, showed typical features of cAMR with positive c4d staining on histology.

*Conclusions: This retrospective analysis in a population of adult and pediatric long term liver transplant recipients supports the hypothesis that very low immunosuppressive treatment is associated with emergence of DSA class II. Furthermore, during long-term follow-up the presence of DSA class II increased the risk of developing liver fibrosis, chronic rejection and graft loss.

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To cite this abstract in AMA style:

Sterneck M, Sultani B, Ozga A, Weidemann S, Hermann J, Grabhorn E, Herden U, Fischer L. Development of DSA Class II is Associated with Immunosuppressive Monotherapy and Increased Risk for Graft Fibrosis, Chronic Rejection and Graft Loss [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/development-of-dsa-class-ii-is-associated-with-immunosuppressive-monotherapy-and-increased-risk-for-graft-fibrosis-chronic-rejection-and-graft-loss/. Accessed May 16, 2025.

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