Published online Mar 27, 2021. doi: 10.4254/wjh.v13.i3.362
Peer-review started: August 14, 2020
First decision: December 11, 2020
Revised: December 27, 2020
Accepted: March 12, 2021
Article in press: March 12, 2021
Published online: March 27, 2021
Immunosuppression is a cornerstone in liver transplantation (LT) and current immunosuppressive regimens are mostly based on tacrolimus. At present, side effects relating anticalcineurin inhibitors are one of the main concerns for long-term outcomes after LT. Side effects are commonly related with drug dose and trough levels.
Tacrolimus trough levels (TTL) above 10 ng/mL during the first weeks after liver transplant have been related with mid and long-term outcomes including impairment of renal function and an increased rate of hepatocellular recurrence, de novo tumors and new-onset diabetes.
The aim of this study was to assess the influence of the TTL during the early post-transplant period in the long-term outcomes of LT.
This was a retrospective study of 155 consecutive liver transplants treated with an immunosuppressive regimen based on de novo once-daily tacrolimus. Patients were classified into 2 groups according to their mean TTL within the first month after transplantation: ≤ 10 ng/mL (n = 98) and > 10 ng/mL (n = 57). All TTL obtained during the first month were used to define the mean values. Multivariate analyses were performed to assess risk factors for patient mortality.
TTL were significantly different among groups only during the first month after transplantation, but not during the rest of the follow-up After a median follow-up of 52.8 mo (range 2.8-81.1), no significant differences were observed in the evolution of the mean estimated glomerular filtration rate, hepatocellular carcinoma recurrence, development of de novo tumors, new-onset diabetes, new-onset arterial hypertension or biopsy-proven acute rejection rate. Five-year patient and graft survival were comparable. Early tacrolimus trough level was not an independent factor for patient mortality in multivariate analyses.
Differences in tacrolimus levels restricted to the first month after transplantation did not result in significant differences in long-term outcomes of liver transplant recipients.
Mid and long-term calcineurin inhibitors-related side effects after LT should be studied considering the cumulative exposure to tacrolimus along the follow-up and not only the trough levels observed during the early post-transplant period.