Frontiers in immunology · 2026
Donor-derived cell-free DNA as a noninvasive biomarker for diagnosis and monitoring of acute rejection after liver transplantation.
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Deng Zhigao, Yang Meicheng, Cheng Quanwei, Lu Zhongshan, Ye Qifa, Xiong Yan, Ye Shaojun
Аннотация
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.
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.