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Diagnostic accuracy of donor-derived cell-free DNA for rejection following liver transplantation: a systematic review and meta-analysis

Transplant Rev (Orlando). 2026 Mar 3;40(3):101008. doi: 10.1016/j.trre.2026.101008. Online ahead of print.

ABSTRACT

BACKGROUND: Graft rejection following liver transplantation remains a major complication affecting long-term survival. Current monitoring strategies, which rely on liver function tests and invasive biopsies, have inherent limitations, creating a need for non-invasive biomarkers. Donor-derived cell-free DNA (dd-cfDNA) has shown promise for monitoring rejection in solid organ transplantation, but its diagnostic accuracy in liver transplantation requires systematic evaluation.

OBJECTIVE: To comprehensively assess the diagnostic accuracy of dd-cfDNA for rejection after liver transplantation via a systematic review and meta-analysis.

METHODS: A comprehensive literature search was conducted in PubMed, Web of Science, Embase, and the Cochrane Library for studies published up to November 26, 2025. Studies were selected based on predefined inclusion and exclusion criteria. Data were extracted, and study quality was assessed. Pooled sensitivity, specificity, and other diagnostic measures were calculated. A summary receiver operating characteristic curve (SROC) was constructed, and heterogeneity along with subgroup analyses were performed.

RESULTS: Eleven studies were included. The meta-analysis demonstrated that dd-cfDNA achieved a pooled sensitivity of 0.90 (95% CI 0.76-0.96) and a pooled specificity of 0.90 (95% CI 0.82-0.94) for diagnosing acute rejection, with an area under the SROC curve of 0.95.

CONCLUSIONS: Dd-cfDNA demonstrates promising diagnostic value as a complementary noninvasive biomarker for rejection after liver transplantation. However, significant heterogeneity in diagnostic thresholds exists across studies. Large-scale, multicenter studies are required in the future to validate its clinical utility.

PMID:41795313 | DOI:10.1016/j.trre.2026.101008

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