{
  "abstract": "Introduction: Acute rejection remains the most common complication during the early post-transplantation period for pediatric patients. Given the limitations of current diagnostic strategies, there is an urgent need to develop accurate and noninvasive biomarkers for allograft monitoring. Tacrolimus-based immunosuppression represents the cornerstone regimen following liver transplantation. However, for pediatric patients, current evidence remains insufficient to establish well-defined therapeutic target ranges for personalized tacrolimus therapy in pediatric patients. We investigated perioperative graft-derived cell-free DNA (GcfDNA) kinetics in pediatric recipients to establish the utility of GcfDNA for monitoring acute rejection and to explore the tacrolimus target concentration range in this population.\n\nMethods: Forty children (age ≤ 3 years) with biliary atresia who underwent liver transplantation were enrolled. All received a tacrolimus-based immunosuppressive regimen on postoperative day (POD) 1 and were followed for at least 1 month. GcfDNA levels were measured by droplet digital PCR.\n\nResults: GcfDNA (%) declined significantly during the first month. Median percentages on POD 1, 7, 14, 21, and 28 were 41.40%, 12.93%, 6.86%, 5.95%, and 3.23%, respectively. The acute rejection group maintained higher GcfDNA levels, with significant differences observed at POD 14, 21, and 28 ( P < 0.001). GcfDNA (%) was strongly correlated with rejection activity index score (r = 0.854, P < 0.001). In this exploratory single-center analysis, receiver operating characteristic (ROC) curve analysis identified an optimal GcfDNA cutoff of 10.21% for predicting acute rejection, with an area under the curve (AUC) of 0.757 (95% CI: 0.691–0.823, P < 0.001). The optimal tacrolimus trough concentration (C ₀ ) threshold was 7.75 ng/mL (AUC = 0.732, 95% CI: 0.655–0.810, P < 0.001).\n\nConclusion: We suggest that GcfDNA may serve as a potential biomarker for acute rejection monitoring in pediatric liver transplantation, with an exploratory predictive cutoff value of 10.21% identified in this single-center cohort. Our findings also tentatively point to a minimal effective tacrolimus C ₀ of 7.75 ng/mL within the first month post-transplantation, alongside an upper safety limit of 10 ng/mL that is primarily grounded in published peer-reviewed literatures. These thresholds, however, were optimized against stable grafts rather than the full spectrum of graft injury and require multicenter validation before clinical adoption.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Science and Education, Tianjin First Central Hospital , ,",
    "Department of Pharmacy, Tianjin Chest Hospital , ,",
    "Department of Liver Transplantation, Organ Transplantation Center, Tianjin First Central Hospital , ,",
    "S&KM Biotechnology Co., Ltd. , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Meiling Yan"
    },
    {
      "affs": [
        1
      ],
      "name": "Jia Zhao"
    },
    {
      "affs": [
        2
      ],
      "name": "Wei Gao"
    },
    {
      "affs": [
        0
      ],
      "name": "Yinpeng Qin"
    },
    {
      "affs": [
        3
      ],
      "name": "Jun Lu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yi Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1fh0pm9tsbxwy.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1939581",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662168/?tool=EBI",
  "id": "1fh0pm9tsbxwy",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13662168",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2746|Organ Transplantation Techniques and Outcomes"
    ]
  ],
  "openalex": "W7203965894",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662168/pdf/?tool=EBI",
  "pmcid": "PMC13662168",
  "pmid": null,
  "published": "2026-09-30",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/1fh0pm9tsbxwy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:20Z",
      "native_id": "PMC:PMC13662168",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13662168"
    },
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1939581",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1939581/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Organ Transplantation Techniques and Outcomes",
      "subfield": "surgery"
    }
  ],
  "title": "Dynamic kinetics of graft-derived cell-free DNA and personalized tacrolimus target ranges for acute rejection monitoring in pediatric liver transplantation",
  "title_text": "Dynamic kinetics of graft-derived cell-free DNA and personalized tacrolimus target ranges for acute rejection monitoring in pediatric liver transplantation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:06Z",
  "url": "https://research.draconitic.com/paper/1fh0pm9tsbxwy",
  "venue": "Frontiers in pharmacology",
  "versions": []
}