ArticleFrontiers in immunology2026
Donor-derived cell-free DNA as a noninvasive biomarker for diagnosis and monitoring of acute rejection after liver transplantation.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background and aims: Acute rejection (AR) is a common complication after liver transplantation. Current diagnostic modalities for acute rejection are either invasive or lack sufficient sensitivity. Therefore, the present study aimed to develop a novel and sensitive diagnostic tool for predicting AR after liver transplantation. Specifically, we investigated whether serum donor-derived cell-free DNA (dd-cfDNA) is closely associated with the occurrence of post-transplant AR. Methods: A prospective single-center diagnostic study enrolled 40 primary whole liver transplant recipients, divided into an indicative biopsy cohort (abnormal liver function requiring biopsy) and a protocol biopsy cohort (stable/mildly abnormal liver function without biopsy indication). The dd-cfDNA levels (absolute copy number and relative quantification) were dynamically monitored 14 days to 1 year post-transplant. Using pathological biopsy as the gold standard, receiver operating characteristic (ROC) curve analysis and logistic regression models compared the diagnostic efficacy of dd-cfDNA and liver function indices for AR. Results: Our study demonstrated that circulating dd-cfDNA levels were significantly elevated in liver transplant recipients with acute rejection (AR) compared to those without. The diagnostic cutoffs were determined as dd-cfDNA% ≥10.39% (sensitivity: 95%, specificity: 90%) and dd-cfDNA ≥1928 copies/mL (sensitivity: 70%, specificity: 90%). The area under the curve (AUC) for dd-cfDNA% was 0.940, and for dd-cfDNA was 0.823, both outperforming routine liver function tests. After effective anti-rejection therapy, dd-cfDNA levels rapidly decreased, correlating with clinical improvement, as well as improvements in liver function and histopathology. Conclusions: As a sensitive and non-invasive biomarker, dd-cfDNA can effectively predict the occurrence of AR after liver transplantation. Moreover, changes in dd-cfDNA levels facilitate the assessment of therapeutic efficacy, providing crucial references for optimizing immunosuppressive regimens and improving patient outcomes.
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