Early tacrolimus exposure does not impact long-term outcomes after liver transplantation.

Background: Tacrolimus trough levels (TTL) during the first weeks after liver transplantation (LT) have been related with long-term renal function and hepatocellular carcinoma recurrence. Nevertheless, the significance of trough levels of tacrolimus during the early post-transplant period for the long-term outcome is under debate.

Aim: To evaluate the effect of TTL during the first month on the long-term outcomes after LT.

Methods: One hundred fifty-five LT recipients treated with once-daily tacrolimus were retrospectively studied. Patients with repeated LT or combined transplantation were excluded as well as those who presented renal dysfunction prior to transplantation and/or those who needed induction therapy. Patients were classified into 2 groups according to their mean TTL within the first month after transplantation: ≤ 10 ( = 98) and > 10 ng/mL ( = 57). Multivariate analyses were performed to assess risk factors for patient mortality.

Results: Mean levels within the first month post-transplant were 7.4 ± 1.7 and 12.6 ± 2.2 ng/mL in the ≤ 10 and > 10 groups, respectively. Donor age was higher in the high TTL group 62.9 ± 16.8 years 45.7 ± 17.5 years ( = 0.002) whilst mycophenolate-mofetil was more frequently used in the low TTL group 32.7% 15.8% ( = 0.02). Recipient features were generally similar across groups. After a median follow-up of 52.8 mo (range 2.8-81.1), no significant differences were observed in: Mean estimated glomerular filtration rate ( = 0.69), hepatocellular carcinoma recurrence ( = 0.44), tumors ( = 0.77), new-onset diabetes ( = 0.13), or biopsy-proven acute rejection rate (12.2% and 8.8%, respectively; = 0.50). Eighteen patients died during the follow-up and were evenly distributed across groups ( = 0.83). Five-year patient survival was 90.5% and 84.9%, respectively ( = 0.44), while 5-year graft survival was 88.2% and 80.8%, respectively ( = 0.42). Early TTL was not an independent factor for patient mortality in multivariate analyses.

Conclusion: Differences in tacrolimus levels restricted to the first month after transplant did not result in significant differences in long-term outcomes of LT recipients.