{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:50:00Z","timestamp":1791971400954,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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":["Pediatric Transplantation"],"published-print":{"date-parts":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Cytomegalovirus (CMV) remains one of the most significant infectious complications after pediatric liver transplantation (LT). Although preemptive therapy (PET) is an effective and widely supported strategy, the choice of a clinically actionable CMV\u2010DNA threshold varies substantially among centers. We aimed to evaluate below\u2010standard CMV\u2010DNA thresholds able to accurately predict clinically significant infection (CSI) while preventing overtreatment in children after LT.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In this prospective observational study, 66 children were followed for 6\u2009months post\u2010LT with scheduled whole\u2010blood CMV\u2010DNA monitoring. CMV\u2010DNA trajectories were evaluated using mixed\u2010effects spline models and compared by clinical outcome and serologic risk. Threshold performance was assessed through interpolated viral\u2010load curves for all infected patients. Sensitivity, overtreatment rate, and positive predictive value (PPV) were estimated for the candidate thresholds.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n CSI occurred in 19\/66 patients (28.7%), while 28 had abortive infections (AI), and 19 showed no infection. CSI displayed significantly higher and more sustained CMV\u2010DNA trajectories compared with AI (\n p<\/jats:italic>\n \u2009<\u20090.0001). Serologic risk did not modify viral kinetics. Threshold analysis identified 40\u2009000\u2009IU\/mL (57\u2009140 copies\/mL) as the optimal PET cut\u2010off: it treated all CSI cases (sensitivity 94.7%, 95% CI 88.9\u2013100), resulted in no overtreatment, and maintained high PPV (100%). Lower thresholds increased overtreatment (up to >\u200950%), while higher ones added no clinical advantage.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n A CMV\u2010DNA threshold of 40\u2009000\u2009IU\/mL in whole blood optimally balances timely PET initiation with avoidance of unnecessary antiviral therapy. These findings support a standardized, clinically pragmatic approach to PET in pediatric LT.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/petr.70472","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:04:45Z","timestamp":1791968685000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimized Cytomegalovirus\u2010\n DNA<\/scp>\n Threshold for Preemptive Therapy in Pediatric Liver Transplant Recipients: A Mixed\u2010Effects Model\u2010Based Analysis of Prospective Cohort Data"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1660-5203","authenticated-orcid":false,"given":"Matteo","family":"Pelucchi","sequence":"first","affiliation":[{"name":"Pediatric Hepatology, Gastroenterology and Transplantation ASST Papa Giovanni XXIII Bergamo Italy"},{"name":"Pediatrics University of Milan Bicocca Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Severi","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology, Gastroenterology and Transplantation ASST Papa Giovanni XXIII Bergamo Italy"},{"name":"Pediatrics University of Milan Bicocca Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Totaro","sequence":"additional","affiliation":[{"name":"Microbiology and Virology ASST Papa Giovanni XXIII Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0602-0155","authenticated-orcid":false,"given":"Francesco","family":"Morotti","sequence":"additional","affiliation":[{"name":"Neonatology and NICU ASST Spedali Civili Hospital Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Passera","sequence":"additional","affiliation":[{"name":"Microbiology and Virology ASST Papa Giovanni XXIII Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Francavilla","sequence":"additional","affiliation":[{"name":"FROM Research Foundation Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0363-5565","authenticated-orcid":false,"given":"Angelo Di","family":"Giorgio","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Pediatrics University of Udine Udine Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Tebaldi","sequence":"additional","affiliation":[{"name":"Infectious Diseases ASST Papa Giovanni XXIII Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Enrico Giovanni","family":"Arosio","sequence":"additional","affiliation":[{"name":"Microbiology and Virology ASST Papa Giovanni XXIII Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6178-5460","authenticated-orcid":false,"given":"Cristina","family":"Russo","sequence":"additional","affiliation":[{"name":"Microbiology and Diagnostic Immunology Unit IRCCS Bambino Ges\u00f9 Children's Hospital Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4426-0395","authenticated-orcid":false,"given":"Andrea","family":"Pietrobattista","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases and Hepatology IRCCS Bambino Ges\u00f9 Children's Hospital Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4092-9071","authenticated-orcid":false,"given":"Marco","family":"Sciveres","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases and Hepatology IRCCS Bambino Ges\u00f9 Children's Hospital Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele Di","family":"Carlo","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pathology, Microbiology and Virology, IRCCS\u2010ISMETT University of Pittsburgh Medical Center Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5895-7257","authenticated-orcid":false,"given":"Giusy","family":"Ranucci","sequence":"additional","affiliation":[{"name":"Pediatric Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS\u2010ISMETT University of Pittsburgh Medical Center Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6549-4553","authenticated-orcid":false,"given":"Cristina","family":"Costa","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Laboratory Medicine AOU Citt\u00e0 Della Salute e Della Scienza Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5077-5531","authenticated-orcid":false,"given":"Michele","family":"Pinon","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology Unit Regina Margherita Children's Hospital, AOU Citt\u00e0 Della Salute e Della Scienza Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Bravi","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology, Gastroenterology and Transplantation ASST Papa Giovanni XXIII Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc Garcia","family":"Lorenzo","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology, Gastroenterology and Transplantation ASST Papa Giovanni XXIII Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6477-6965","authenticated-orcid":false,"given":"Ezio","family":"Bonanomi","sequence":"additional","affiliation":[{"name":"Pediatric Intensive Care Unit ASST Papa Giovanni XXIII Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3564-9953","authenticated-orcid":false,"given":"Domenico","family":"Pinelli","sequence":"additional","affiliation":[{"name":"3rd Surgery Unit ASST Papa Giovanni XXIII Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7150-3148","authenticated-orcid":false,"given":"Lorenzo","family":"D\u2019Antiga","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology, Gastroenterology and Transplantation ASST Papa Giovanni XXIII Bergamo Italy"},{"name":"Pediatrics University of Milan Bicocca Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4518-9375","authenticated-orcid":false,"given":"Emanuele","family":"Nicastro","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology, Gastroenterology and Transplantation ASST Papa Giovanni XXIII Bergamo Italy"},{"name":"Department of Medicine and Surgery, Pediatrics, Hospital \u201cF. Del Ponte\u201d University of Insubria Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"3497","DOI":"10.2174\/1381612826666200531152901","article-title":"Cytomegalovirus in Solid Organ Transplant Recipients: Clinical Updates, Challenges and Future Directions","volume":"26","author":"Razonable R. R.","year":"2020","journal-title":"Current Pharmaceutical Design"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1097\/MOT.0000000000000433","article-title":"Cytomegalovirus in Liver Transplant Recipients","volume":"22","author":"Herman D.","year":"2017","journal-title":"Current Opinion in Organ Transplantation"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1097\/TP.0000000000001531","article-title":"Effectiveness of Preemptive Therapy for Cytomegalovirus Disease in Pediatric Liver Transplantation","volume":"101","author":"Nicastro E.","year":"2017","journal-title":"Transplantation"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1001\/jama.2020.3138","article-title":"Effect of Preemptive Therapy vs Antiviral Prophylaxis on Cytomegalovirus Disease in Seronegative Liver Transplant Recipients With Seropositive Donors: A Randomized Clinical Trial","volume":"323","author":"Singh N.","year":"2020","journal-title":"JAMA"},{"key":"e_1_2_7_6_1","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1093\/cid\/ciad643","article-title":"Association of Cytomegalovirus (CMV) DNAemia With Long\u2010Term Mortality in a Randomized Trial of Preemptive Therapy and Antiviral Prophylaxis for Prevention of CMV Disease in High\u2010Risk Donor Seropositive, Recipient Seronegative Liver Transplant Recipients","volume":"78","author":"Kumar L.","year":"2024","journal-title":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1097\/TP.0000000000002191","article-title":"The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid\u2010Organ Transplantation","volume":"102","author":"Kotton C. N.","year":"2018","journal-title":"Transplantation"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1097\/00007890-199910270-00011","article-title":"Cytomegalovirus PP65 Antigenemia Monitoring as a Guide for Preemptive Therapy: A Cost Effective Strategy for Prevention of Cytomegalovirus Disease in Adult Liver Transplant Recipients","volume":"68","author":"Kusne S.","year":"1999","journal-title":"Transplantation"},{"key":"e_1_2_7_9_1","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1093\/infdis\/173.2.446","article-title":"Prognostic Significance and Risk Factors of Untreated Cytomegalovirus Viremia in Liver Transplant Recipients","volume":"173","author":"Badley A. D.","year":"1996","journal-title":"Journal of Infectious Diseases"},{"key":"e_1_2_7_10_1","doi-asserted-by":"crossref","DOI":"10.1002\/jmv.70347","article-title":"Cytomegalovirus\u2010RNA Accurately Identifies Clinically Significant Infection Needing Preemptive Therapy in Liver Transplanted Children: A Proof\u2010Of\u2010Concept Study","volume":"97","author":"Nicastro E.","year":"2025","journal-title":"Journal of Medical Virology"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1111\/j.1600-6143.2012.04087.x","article-title":"Cytomegalovirus Replication Kinetics in Solid Organ Transplant Recipients Managed by Preemptive Therapy","volume":"12","author":"Atabani S. F.","year":"2012","journal-title":"American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jcv.2012.09.017","article-title":"Determination, Validation and Standardization of a CMV DNA Cut\u2010Off Value in Plasma for Preemptive Treatment of CMV Infection in Solid Organ Transplant Recipients at Lower Risk for CMV Infection","volume":"56","author":"Mart\u00edn\u2010Gandul C.","year":"2013","journal-title":"Journal of Clinical Virology: The Official Publication of the Pan American Society for Clinical Virology"},{"key":"e_1_2_7_13_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0163722","article-title":"Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre\u2010Emptive Therapy","volume":"11","author":"Griffiths P. D.","year":"2016","journal-title":"PLoS One"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1111\/tri.12378","article-title":"Viral Load, CMV\u2010Specific T\u2010Cell Immune Response and Cytomegalovirus Disease in Solid Organ Transplant Recipients at Higher Risk for Cytomegalovirus Infection During Preemptive Therapy","volume":"27","author":"Mart\u00edn\u2010Gandul C.","year":"2014","journal-title":"Transplant International: Official Journal of the European Society for Organ Transplantation"},{"key":"e_1_2_7_15_1","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.jcv.2012.10.015","article-title":"Quantification of Cytomegalovirus DNA by a Fully Automated Real\u2010Time PCR for Early Diagnosis and Monitoring of Active Viral Infection in Solid Organ Transplant Recipients","volume":"56","author":"Boaretti M.","year":"2013","journal-title":"Journal of Clinical Virology: The Official Publication of the Pan American Society for Clinical Virology"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.biologicals.2016.04.005","article-title":"A Collaborative Study to Establish the 1st WHO International Standard for Human Cytomegalovirus for Nucleic Acid Amplification Technology","volume":"44","author":"Fryer J. F.","year":"2016","journal-title":"Biologicals: Journal of the International Association of Biological Standardization"},{"key":"e_1_2_7_17_1","first-page":"715","article-title":"ESPGHAN 52nd Annual Meeting Abstracts","volume":"68","author":"Nicastro E.","year":"2019","journal-title":"Journal of Pediatric Gastroenterology and Nutrition"},{"key":"e_1_2_7_18_1","doi-asserted-by":"crossref","DOI":"10.1111\/ctr.13666","article-title":"Assessment and Prevention of Cytomegalovirus Infection in Allogeneic Hematopoietic Stem Cell Transplant and in Solid Organ Transplant: A Multidisciplinary Consensus Conference by the Italian GITMO, SITO, and AMCLI Societies","volume":"33","author":"Girmenia C.","year":"2019","journal-title":"Clinical Transplantation"},{"key":"e_1_2_7_19_1","unstructured":"Human Cytomegalovirus (HCMV) for Nucleic Acid Amplification Techniques (1st International Standard) 2024accessed at https:\/\/nibsc.org\/products\/brm_product_catalogue\/detail_page.aspx?catid=09\/162."},{"key":"e_1_2_7_20_1","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/TP.0b013e31817889e4","article-title":"Prophylaxis Followed by Preemptive Therapy Versus Preemptive Therapy for Prevention of Human Cytomegalovirus Disease in Pediatric Patients Undergoing Liver Transplantation","volume":"86","author":"Gerna G.","year":"2008","journal-title":"Transplantation"},{"key":"e_1_2_7_21_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1177\/135965350701200108","article-title":"Evaluation of Cytomegalovirus DNAaemia Versus pp65\u2010Antigenaemia Cutoff for Guiding Preemptive Therapy in Transplant Recipients: A Randomized Study","volume":"12","author":"Gerna G.","year":"2007","journal-title":"Antiviral Therapy"},{"key":"e_1_2_7_22_1","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1002\/jmv.20107","article-title":"Clinically\u2010Based Determination of Safe DNAemia Cutoff Levels for Preemptive Therapy or Human Cytomegalovirus Infections in Solid Organ and Hematopoietic Stem Cell Transplant Recipients","volume":"73","author":"Lilleri D.","year":"2004","journal-title":"Journal of Medical Virology"},{"key":"e_1_2_7_23_1","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.3758\/s13428-023-02133-1","article-title":"Alternative Covariance Structures in Mixed\u2010Effects Models: Addressing Intra\u2010 and Inter\u2010Individual Heterogeneity","volume":"56","author":"Blozis S. 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