Korean J Transplant.  2022 Nov;36(Supple 1):S156. 10.4285/ATW2022.F-2755.

Effect of cumulative exposure to tacrolimus on the recurrence of hepatocellular carcinoma after liver transplantation

• Kim DG
• Lee JG
• Joo DJ
• Kim MS

• KMID: 2535672
• DOI: http://doi.org/10.4285/ATW2022.F-2755

Abstract

Background
Previous studies reported that maintaining at lower trough level of tacrolimus could reduce the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT); however, this has never been assessed regarding everyday exposure of tacrolimus.
Methods
Using whole data of tacrolimus trough levels, which were measured at in-hospital and outpatient setting, we calcu-lated cumulative exposure to tacrolimus (CET) by the formula recently introduced. Eligible patients who underwent LT for HCC n=504) were divided into four groups by CET within 3 months after LT; high (3-month CET>840, n=101), conventional (3-month CET 580–839, n=215), minimization (3-month CET 321–579, n=158), and aggressive minimization (3-month CET<320, n=30).
Results
In Kaplan-Meier analyses, the 5-year recurrence free survival was not significantly different between the four groups (P=0.770) while that of patient survival was significantly lower in the aggressive minimization group and the high exposure group (P=0.005). In multivariable analyses, neither groups by CET nor CET as continuous variable did not affect the recurrence of HCC. However, the aggressive minimization (hazard ratio [HR], 2.97; P=0.011) and the high exposure group (HR, 1.89; P=0.023) showed significantly higher risk of death when compared with conventional exposure group. Subgroups stratified by Milan criteria, upto-7, french high risk model, preoperative systemic therapy and treatment with mTOR inhibitor did not show significantly different recurrent free survival between CET groups.
Conclusions
In this study, CET did not affect the recurrence of HCC after LT while aggressive minimization and high exposure of tacrolimus resulted in higher death. Usage of tacrolimus should not target to reduce HCC recurrence but to prevent rejection.