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. 2025 Sep;50(5):371-381.
doi: 10.1007/s13318-025-00954-3. Epub 2025 Jun 17.

Tacrolimus Trough Concentrations are Not Impacted by Epstein-Barr Virus Serology and Viral Load in Pediatric Liver Transplant Recipients

Amber M Te Lintelo #  1 , Lisa F van Wier #  1 , Hubert P J van der Doef  2 , Jos G W Kosterink  1   3 , René Scheenstra  2 , Coretta C van Leer  4 , Arno R Bourgonje  5   6 , Daan J Touw  1   7 , Paola Mian  8   9
Affiliations

Tacrolimus Trough Concentrations are Not Impacted by Epstein-Barr Virus Serology and Viral Load in Pediatric Liver Transplant Recipients

Amber M Te Lintelo et al. Eur J Drug Metab Pharmacokinet. 2025 Sep.

Abstract

Background and objectives: Epstein-Barr virus (EBV) is a common herpesvirus among pediatric liver transplant recipients, but it can have serious complications, such as post-transplant lymphoproliferative disease. EBV is hypothesized to influence tacrolimus concentrations by increasing inflammatory cytokines that regulate the expression of cytochrome-P-450 enzymes involved in tacrolimus pharmacokinetics. This study aims to examine the association between EBV serostatus and viral load, and tacrolimus trough concentrations corrected for the dose and recipient weight [weight-adjusted concentration-to-dose (C/D) ratios].

Materials and methods: This retrospective study includes pediatric liver transplant recipients aged 0-18 years old, transplanted at the University Medical Center Groningen between January 2008 and September 2021. This study utilized two cohorts: a cross-sectional and a longitudinal study database.

Results: The association between EBV serostatus and the tacrolimus pharmacokinetics was examined using 45 recipients from both cohorts. The effect of EBV viral load on tacrolimus pharmacokinetics was examined using the longitudinal study database, which included 25 EBV-positive recipients. No significant effect of EBV on the tacrolimus weight-adjusted C/D ratios was found, for either EBV serostatus (p = 0.85) or EBV viral load (p = 0.85).

Conclusions: This study suggests that the standard protocol of tacrolimus dosing does not seem to require adjustments due to changes in EBV serostatus or viral load.

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Conflict of interest statement

Declarations. Conflict of Interest: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Ethics Approval: This is a retrospective and descriptive study. The Medical Ethics Review Board of the University Medical Center Groningen (METc UMCG) has confirmed that this study does not fall under the scope of the Medical Research Involving Human Subjects Act (WMO), and therefore, no WMO required (METc 2019/621). Consent to Participate: Due to the retrospective and descriptive nature of this study, the need for informed consent was waived by the UMCG METc (METc 2019/621). Consent for Publication: No identifiable personal data is included in this study; therefore, consent for publication was not required. Code Availability: The data used in this study is owned by the UMCG and is not publicly available. No custom code was developed for this study. Authors’ Contribution Statements: Amber M. B. te Lintelo and Lisa F. van Wier contributed equally to this work. They were responsible for literature research, data extraction, data analysis, and writing the initial draft of the manuscript. Paola Mian, Daan J. Touw, and Hubert P. J. van der Doef contributed to the conceptualization of the study, data analysis, and writing and reviewing the manuscript. Coretta C. van Leer, René Scheenstra, Arno R. Bourgonje, and Jos. G. W. Kosterink contributed to reviewing the manuscript. All authors approved the final version of the manuscript.

Figures

Fig. 1
Fig. 1
Flow-chart indicating the specific inclusion criteria for both the cross-sectional and longitudinal study populations, with various study cohorts indicated alongside their specific aims and the corresponding number of enrolled liver transplantation recipients. C/D concentration-to-dose, EBV Epstein–Barr virus, EBV+ EBV-positive, n number of recipients, UMCG University Medical Center Groningen. *included from longitudinal study database, to examine the secondary aim: the effect of EBV viral load on the tacrolimus weight-adjusted C/D ratio
Fig. 2
Fig. 2
The interpatient association between EBV serostatus and the tacrolimus weight-adjusted C/D ratio in the longitudinal database. The figure includes patients that remained EBV-negative and patients that remained EBV-positive during longitudinal follow-up. C/D concentration-to-dose, EBV Epstein–Barr virus, EBV− EBV-negative, EBV+ EBV-positive, n number of patients
Fig. 3
Fig. 3
The intrapatient association between EBV serostatus and the tacrolimus weight-adjusted C/D ratio in the cross-sectional and longitudinal database. Recipients who converted from EBV-negative to EBV-positive were included. No significant difference was observed between EBV-negative and EBV-positive recipients. C/D concentration-to-dose, EBV Epstein–Barr virus, EBV− EBV-negative, EBV+ EBV-positive, n number of patients
Fig. 4
Fig. 4
The intrapatient association between EBV viral load and the tacrolimus weight-adjusted C/D ratio in the cross-sectional and longitudinal databases. No significant difference was observed between the groups. C/D concentration-to-dose, EBV Epstein–Barr virus, n number of patients
See this image and copyright information in PMC

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