BackgroundThe intra-patient variability in tacrolimus exposure (TAC-IPV) after paediatric liver transplantation and its impact on patient outcomes has been poorly studied. The present study aims to investigate whether there is a trend in TAC-IPV during the first 5 years post transplantation, which variables influence IPV and wheth-er the IPV during the first year is associated with liver transplantation outcomes in paediatric patients.MethodsWe conducted a single centre retrospective study including 41 living paediatric patients transplanted between January 2003 and September 2016 at the Ghent University Hospital. The intra-patient variability in the dose-adjusted tacrolimus pre-dose concentrations was calculated yearly during the first five years following trans-plantation, expressed as coefficient of variation (CV%1–5) The difference in CV% in the years following transplanta-tion was analysed using the Friedman test. A linear uni-variate and multivariate regression analysis was applied to identify factors associated with TAC-IPV. The following parameters were tested: age, gender, origin, the number of missed clinic appointments as a surrogate marker for ther-apy adherence, the total number of medications, concom-itant medications potentially interfering with TAC metabo-lism-CYP3A4/A5 inductors or inhibitors and biochemical parameters. Logistic and linear regression models were fit-ted to test an association of TAC-IPV with patient outcomes: need for biopsy during year 1, 3 and 5; hypertension and renal function at 1, 3 and 5 years; acute rejection and CMV/EBV viremia during year 1 post-transplantation.ResultsWe identified a significant decrease in TAC-IPV during the first 3 years after transplantation with the me-dian CV%1=39,4%; CV%2=30,9%; CV%3=28,5% (p=0,004), after which the CV% reaches a plateau (CV%4=23,6% en CV%5=28,9%). Multivariate analysis showed that serum albumin in the first year (p=0,029), haematocrit in the third year (p=0,019) and the number of missed clin-ic appointments in the fifth year after transplantation (p=0,009) were associated with TAC-IPV.in the 1 st, 3rd and 5th year, respectively. Univariate analysis showed that CV%1 was significantly associated with the need for bi-opsy during the first year post-transplantation (p=0.036) and the occurrence of one or more episodes of acute al-lograft rejection during the first year post-transplantation (p=0.031). In univariate analysis a trend was observed for association with hypertension one year after transplan-tation (p=0,085). Multivariate logistic regression analysis confirmed that CV%1 was an independent factor associ-ated with the need for liver biopsy in the first year follow-ing liver transplantation. (p=0.05; Exp(B)=1.045).ConclusionAs expected, tacrolimus intra-patient vari-ability is higher during the first two years after transplantation. Our results suggest that while albumin and hae-matocrit are associated with TAC-IPV in the first 3 years, therapy adherence expressed as the number of missed clinic appointments is associated with TAC...