{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:26:32Z","timestamp":1791563192642,"version":"4.3.4"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cross\u2010sectional tacrolimus concentrations and liver biochemistry may not reflect longitudinal instability after paediatric liver transplantation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To derive a risk score based on pharmacokinetic and biochemical variability at one centre and validate it at an independent centre.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective two\u2010centre landmark study included 93 recipients, predominantly infants with biliary atresia (83.9%) undergoing primary liver transplantation, the majority receiving living\u2010donor grafts (88.2%), and 86 recipients in the validation cohort (76.7% biliary atresia; 45.3% living\u2010donor). Variability in tacrolimus trough concentrations, aspartate aminotransferase and total bilirubin was calculated from measurements obtained 6\u201312\u2009months after transplantation. Patients with major complications during this period were excluded. Follow\u2010up began at 12\u2009months. The primary outcome was the first major late complication or death without a preceding qualifying complication. A three\u2010point score was derived and applied unchanged to the external cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nineteen derivation\u2010cohort patients and 12 validation\u2010cohort patients experienced late events. The score assigned one point each for tacrolimus variability above 25%, aspartate aminotransferase variability above 50% and total bilirubin variability above 50%. Scores of 2\u20133 identified higher\u2010risk patients in the derivation cohort, with a hazard ratio of 4.48, a 95% confidence interval of 1.79\u201311.17 and a concordance index of 0.748. Areas under the curve at 1, 3 and 5\u2009years were 0.883, 0.802 and 0.740. In the external cohort, the hazard ratio was 8.90, with a 95% confidence interval of 2.66\u201329.81 and corresponding areas under the curve of 0.753, 0.775 and 0.789.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Integrating the longitudinal variability of tacrolimus exposure and liver biochemistry provides a practical, externally validated, non\u2010invasive tool for paediatric liver transplantation survivors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.70969","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T06:08:01Z","timestamp":1788934081000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetic and Pharmacodynamic Variability Predict Late Events After Paediatric Liver Transplantation: Derivation and External Validation of a Landmark Risk Score"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3067-6779","authenticated-orcid":false,"given":"Haifeng","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9344-8303","authenticated-orcid":false,"given":"Shuguang","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4985-2485","authenticated-orcid":false,"given":"Jiajun","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanhai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoke","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingman","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases  Chongqing 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