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Characterizing Early Donor-Derived cfDNA Kinetics in Stable Pediatric Living-Donor Liver Transplant Recipients
Naresh Shanmugam1, Avinash Ramani2, Bhavani Gunasekaran2
1The Institute of Liver Disease and Transplantation, Dr. Rela Institute and Medical Centre, Chennai, India.
Insights
Donor-derived cell-free DNA (ddcfDNA) shows rapid early clearance in pediatric liver transplant recipients. These findings establish baseline ddcfDNA levels for monitoring graft health non-invasively.
Area of Science:
- Transplant immunology
- Pediatric gastroenterology
- Molecular diagnostics
Background:
- Graft health monitoring in pediatric liver transplant patients relies on invasive methods.
- Donor-derived cell-free DNA (ddcfDNA) is a promising non-invasive biomarker for graft injury.
- Limited data exists on early ddcfDNA kinetics and influencing factors in stable pediatric populations.
Purpose of the Study:
- To characterize early postoperative ddcfDNA patterns in stable pediatric liver transplant recipients.
- To establish baseline ddcfDNA ranges for living donor liver transplants (LDLT).
- To evaluate how recipient and donor factors influence ddcfDNA dynamics for improved non-invasive monitoring.
Main Methods:
- Longitudinal ddcfDNA measurements in 22 stable pediatric LDLT recipients using the Trunome GrafAssure assay.
- Sampling at postoperative days 1-2, 7, 10-14, and 30-31.
- Concurrent collection of liver function tests and clinical data, with statistical analysis.
Main Results:
- ddcfDNA peaked early (days 1-2), declined sharply by day 7, and stabilized by day 30-31.
- Early ddcfDNA levels correlated with AST and ALT, with diminishing associations over time.
- Recipient and donor characteristics did not significantly impact ddcfDNA levels.
Conclusions:
- ddcfDNA exhibits rapid postoperative clearance and stable trends in stable pediatric liver transplant recipients.
- Characterized baseline values and kinetics offer a reference for future studies on graft dysfunction or rejection.
- This provides a framework for non-invasive graft monitoring in early and surveillance periods.
Background:
Early and precise assessment of graft health is vital for pediatric liver transplant patients; however, current monitoring methods depend largely on invasive biopsies and non-specific biochemical tests. Donor-derived cell-free DNA (ddcfDNA) has emerged as a promising non-invasive biomarker for detecting graft injury, but data on its early post-transplant kinetics, baseline levels, and the influence of donor and recipient factors in stable pediatric populations remain limited.
Objective:
To prospectively characterize the early postoperative patterns of ddcfDNA and explore baseline ranges in clinically stable pediatric recipients of living donor liver transplants (LDLT), while evaluating the influence of recipient and donor demographic and clinical variables on ddcfDNA dynamics for improved non-invasive graft monitoring.
Methods:
In a cohort of 22 stable pediatric LDLT recipients, ddcfDNA levels were measured longitudinally using the Trunome GrafAssure assay at postoperative days 1-2, 7, 10-14, and 30-31. Concurrent liver function tests and clinical data were also collected. Statistical analyses were performed to evaluate correlations and determine the significance of the observed relationships.
Results:
ddcfDNA peaked on days 1-2 (~9.0%, 2.3 ng/mL), declined sharply by day 7 (~2.4%, 1.0 ng/mL), and stabilized by days 30-31 (~2.0%, 0.2 ng/mL). Liver enzymes decreased gradually. The absolute quantification values and the ddcfDNA percentage correlated with AST and ALT early post-transplant, with associations diminishing over time. Recipient and donor characteristics did not significantly affect ddcfDNA levels.
Conclusion:
dd-cfDNA demonstrates rapid postoperative clearance and stable longitudinal trends in clinically stable pediatric liver transplant recipients. The baseline values and kinetic patterns characterized provide a preliminary reference framework for future comparative studies evaluating dd-cfDNA behavior during graft dysfunction, rejection, or other adverse events in the early postoperative and surveillance periods.
