Impact of low tacrolimus level on graft rejection, survival, and hepatocellular carcinoma recurrence
- Author:
Hayeon DO
1
;
Namkee OH
;
Jiyoung BAIK
;
Suk Min GWON
;
Youngju RYU
;
Eunjin LEE
;
Sunghyo AN
;
Jinsoo RHU
;
Gyu-Seong CHOI
;
Jae-Won JOH
;
Jongman KIM
Author Information
- Publication Type:Original Article
- From: Annals of Liver Transplantation 2025;5(2):124-133
- CountryRepublic of Korea
- Language:English
-
Abstract:
Background:Tacrolimus is a key immunosuppressant after liver transplantation.Although guideline-recommended trough levels are 4–10 ng/mL, concerns about nephrotoxicity, metabolic complications, and malignancies have led to interest in minimizing tacrolimus use. However, the effects of lower tacrolimus levels on graft rejection and hepatocellular carcinoma (HCC) recurrence remain unclear.
Methods:We conducted a single-center, retrospective study of adult patients (≥19 years) who underwent living donor liver transplantation between January 2000 and December 2021. Patients were divided into low tacrolimus (FK) (<6 ng/mL) and high FK (≥6 ng/mL) groups based on tacrolimus levels measured 1–2 years post-transplantation. We analyzed overall survival, biopsy-proven rejection-free survival, and HCC recurrence-free survival in relevant subgroups. Cox proportional hazards regression identified predictors of mortality, rejection, and HCC recurrence.
Results:Among 1,117 recipients, 941 were in the low FK group and 176 in the high FK group. Landmark analysis showed significantly better 10-year overall survival in the low FK group (82.8% vs. 68.8%, p=0.016), while rejection-free survival did not differ significantly beyond 2 years (p=0.098), despite early separation favoring the low FK group (p<0.001). Higher tacrolimus levels independently predicted increased mortality (hazard ratio [HR]=1.98, 95% confidence interval [CI] 1.35–2.89; p<0.001) and rejection (HR=2.20, 95% CI 1.48–3.27; p<0.001). Among 614 HCC patients, landmark analysis revealed no significant difference in recurrence-free survival (77.7% vs. 81.2%, p=0.288) or overall survival (77.3% vs. 65.8%, p=0.215), and FK levels were not independently associated with either outcome.
Conclusion:Maintaining tacrolimus levels below 6 ng/mL was associated with better survival and rejection outcomes without increasing HCC recurrence, suggesting dose minimization may be feasible in selected patients.
