Immune Monitoring (Videos Available)

Tuesday July 03, 2018 from 09:45 to 11:15

Room: N-106

420.7 Donor-specific cell-free DNA as an emerging biomarker of organ rejection after liver transplantation (Video Available)

Award Winner

Su Kah Goh, Australia has been granted the TTS Young Investigator Scientific Award

Su Kah Goh, Australia

Surgical Registrar
Department of Surgery, Austin Health
University of Melbourne

Abstract

Donor-Specific Cell-Free DNA as an Emerging Biomarker of Organ Rejection after Liver Transplantation.

Su Kah Goh1,3, Hongdo Do3, Vijayaragavan Muralidharan1, Robert Jones1,2, Alexander Dobrovic3, Christopher Christophi1,2.

1Department of Surgery, University of Melbourne, Austin Health, Melbourne, Australia; 2Victorian Liver Transplantation Unit, Austin Health, Melbourne, Australia; 3Translational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, Australia

Introduction: There is an increasing interest in the use of donor-specific cell-free DNA (dscfDNA) as a non-invasive biomarker of organ health after transplantation. We have developed a PCR-based approach that readily measures dscfDNA. Using this approach, we evaluated the utility of dscfDNA in two separate cohorts of recipients.
Methods: Deletion/insertion polymorphisms (DIP) were used to distinguish donor-specific DNA and recipient-specific DNA. Post-transplant dscfDNA was measured using a simple and novel probe-free droplet digital PCR (ddPCR) methodology. In the longitudinal cohort, dscfDNA was serially measured at days 3, 7, 14, 28 and 42 in 20 recipients. In the cross-sectional cohort, dscfDNA was quantified in 16 recipients (>3 months post-transplant) undergoing liver biopsies.
Results: DscfDNA levels were reflective of organ health after liver transplantation. In the recipients who underwent uncomplicated transplantation, dscfDNA markedly reduced at day 7 and remained at a low median level of 76.45 (IQR: 50.60-108.90) dscfDNA copies/mL from day 14 onwards. Furthermore, dscfDNA was consistently lower in recipients who did not have any evidence of rejection compared to those who developed biopsy-proven organ rejection (281.50 dscfDNA copies/mL vs 1,661.00 dscfDNA copies/mL respectively, p<0.05). The area under the receiver operator characteristic curve of dscfDNA was higher compared to routine serum liver biochemistry (dscfDNA: 0.818, ALT: 0.745, GGT: 0.627, ALP: 0.436).
Conclusion: In this study, we demonstrated a readily performed methodology to measure dscfDNA. We also highlighted the utility of dscfDNA as a promising non-invasive biomarker for the surveillance of organ health and the diagnosis of organ rejection after liver transplantation.



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