Pediatric transplantation · 2026
Optimized Cytomegalovirus-DNA Threshold for Preemptive Therapy in Pediatric Liver Transplant Recipients: A Mixed-Effects Model-Based Analysis of Prospective Cohort Data.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Pelucchi Matteo, Severi Eleonora, Totaro Michele, Morotti Francesco, Passera Ilaria, Francavilla Andrea, Giorgio Angelo Di, Tebaldi Alessandra, Arosio Marco Enrico Giovanni, Russo Cristina, Pietrobattista Andrea, Sciveres Marco, Carlo Daniele Di, Ranucci Giusy, Costa Cristina, Pinon Michele, Bravi Michela, Lorenzo Marc Garcia, Bonanomi Ezio, Pinelli Domenico, D'Antiga Lorenzo, Nicastro Emanuele
Аннотация
BACKGROUND: 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-DNA threshold varies substantially among centers. We aimed to evaluate below-standard CMV-DNA thresholds able to accurately predict clinically significant infection (CSI) while preventing overtreatment in children after LT.
METHODS: In this prospective observational study, 66 children were followed for 6 months post-LT with scheduled whole-blood CMV-DNA monitoring. CMV-DNA trajectories were evaluated using mixed-effects spline models and compared by clinical outcome and serologic risk. Threshold performance was assessed through interpolated viral-load curves for all infected patients. Sensitivity, overtreatment rate, and positive predictive value (PPV) were estimated for the candidate thresholds.
RESULTS: 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-DNA trajectories compared with AI (p < 0.0001). Serologic risk did not modify viral kinetics. Threshold analysis identified 40 000 IU/mL (57 140 copies/mL) as the optimal PET cut-off: it treated all CSI cases (sensitivity 94.7%, 95% CI 88.9-100), resulted in no overtreatment, and maintained high PPV (100%). Lower thresholds increased overtreatment (up to > 50%), while higher ones added no clinical advantage.
CONCLUSIONS: A CMV-DNA threshold of 40 000 IU/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.
METHODS: In this prospective observational study, 66 children were followed for 6 months post-LT with scheduled whole-blood CMV-DNA monitoring. CMV-DNA trajectories were evaluated using mixed-effects spline models and compared by clinical outcome and serologic risk. Threshold performance was assessed through interpolated viral-load curves for all infected patients. Sensitivity, overtreatment rate, and positive predictive value (PPV) were estimated for the candidate thresholds.
RESULTS: 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-DNA trajectories compared with AI (p < 0.0001). Serologic risk did not modify viral kinetics. Threshold analysis identified 40 000 IU/mL (57 140 copies/mL) as the optimal PET cut-off: it treated all CSI cases (sensitivity 94.7%, 95% CI 88.9-100), resulted in no overtreatment, and maintained high PPV (100%). Lower thresholds increased overtreatment (up to > 50%), while higher ones added no clinical advantage.
CONCLUSIONS: A CMV-DNA threshold of 40 000 IU/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.