{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:56:52Z","timestamp":1790751412573,"version":"4.1.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Forty children (age \u2264 3\u00a0years) 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\u00a0month. GcfDNA levels were measured by droplet digital PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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 (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001). GcfDNA (%) was strongly correlated with rejection activity index score (r = 0.854,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 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\u20130.823,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001). The optimal tacrolimus trough concentration (C\n                      <jats:sub>0<\/jats:sub>\n                      ) threshold was 7.75\u00a0ng\/mL (AUC = 0.732, 95% CI: 0.655\u20130.810,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:sub>0<\/jats:sub>\n                      of 7.75\u00a0ng\/mL within the first month post-transplantation, alongside an upper safety limit of 10\u00a0ng\/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.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1939581","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:05:50Z","timestamp":1790748350000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic kinetics of graft-derived cell-free DNA and personalized tacrolimus target ranges for acute rejection monitoring in pediatric liver transplantation"],"prefix":"10.3389","volume":"17","author":[{"given":"Meiling","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Science and Education, Tianjin First Central Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tianjin Chest Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Liver Transplantation, Organ Transplantation Center, Tianjin First Central Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinpeng","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Science and Education, Tianjin First Central Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Lu","sequence":"additional","affiliation":[{"name":"S&KM Biotechnology Co., Ltd.","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Science and Education, Tianjin First Central Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.1373\/clinchem.2013.210328","article-title":"Digital droplet PCR for rapid quantification of donor DNA in the circulation of transplant recipients as a potential universal biomarker of graft injury","volume":"59","author":"Beck","year":"2013","journal-title":"Clin. 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