Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 27, 2021; 13(3): 362-374
Published online Mar 27, 2021. doi: 10.4254/wjh.v13.i3.362
Early tacrolimus exposure does not impact long-term outcomes after liver transplantation
Mikel Gastaca, Patricia Ruiz, Javier Bustamante, Lorea Martinez-Indart, Alberto Ventoso, José Ramón Fernandez, Ibone Palomares, Mikel Prieto, Milagros Testillano, Patricia Salvador, Maria Senosiain, Maria Jesus Suárez, Andres Valdivieso
Mikel Gastaca, Patricia Ruiz, Alberto Ventoso, Ibone Palomares, Mikel Prieto, Andres Valdivieso, Department of HPB Surgery and Liver Transplantation Unit, Hospital Universitario Cruces, Bilbao 48903, Spain
Javier Bustamante, José Ramón Fernandez, Milagros Testillano, Patricia Salvador, Maria Senosiain, Maria Jesus Suárez, Department of Hepatology Unit, Hospital Universitario Cruces, Bilbao 48903, Spain
Lorea Martinez-Indart, Department of Bioinformatics and Statistics Platform, Biocruces Bizkaia Health Research Institute, Hospital Universitario Cruces, Bilbao 48903, Spain
Author contributions: Gastaca M designed and performed the research and wrote the paper; Ruiz P and Bustamante J designed the research and supervised the report; Martinez-Indart L provided the statistical analysis; Ventoso A, Palomares I, Prieto M, Salvador P, and Senosiain M acquired and analyzed the data; Testillano M, and Suárez MJ and Valdivieso A supervised the report; all authors approved the final version of the article.
Institutional review board statement: This study was reviewed and approved by the Research Ethics Committee of the Hospital Universitario Cruces, No. CEIC E13/08.
Informed consent statement: Patients gave written consent to be included in the liver transplantation prospective data base. The requirement for specific informed consent for this study was waived because of the retrospective nature of the study.
Conflict-of-interest statement: MG is a member of advisory boards and has received honoraria from Astellas, Novartis and Chiesi. JB has received honoraria from Astellas and Novartis. AV has received honoraria from Astellas and Novartis. All other authors have no conflicts to declare.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mikel Gastaca, MD, Associate Professor, Surgeon, Department of HPB Surgery and Liver Transplantation Unit, Hospital Universitario Cruces, PLaza de Cruces s/n, Bilbao 48903, Spain. mikelgastaca@gmail.com
Received: August 14, 2020
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
Abstract
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 de novo 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 (n = 98) and > 10 ng/mL (n = 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 vs 45.7 ± 17.5 years (P = 0.002) whilst mycophenolate-mofetil was more frequently used in the low TTL group 32.7% vs 15.8% (P = 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 (P = 0.69), hepatocellular carcinoma recurrence (P = 0.44), de novo tumors (P = 0.77), new-onset diabetes (P = 0.13), or biopsy-proven acute rejection rate (12.2% and 8.8%, respectively; P = 0.50). Eighteen patients died during the follow-up and were evenly distributed across groups (P = 0.83). Five-year patient survival was 90.5% and 84.9%, respectively (P = 0.44), while 5-year graft survival was 88.2% and 80.8%, respectively (P = 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.

Keywords: Liver transplantation, Tacrolimus levels, Prolonged released tacrolimus, Once-daily tacrolimus, Renal function, Survival, Outcomes

Core Tip: This is a retrospective study to evaluate the effect of early tacrolimus trough levels (TTL) on the long-term outcomes after liver transplantation. Patients were classified into 2 groups according to mean TTL within the first month: ≤ 10 (n = 98) and > 10 ng/mL (n = 57). 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, hepatocellular carcinoma recurrence, de novo tumors, biopsy-proven acute rejection rate and five-year patient and graft survival. Differences in tacrolimus levels within the first month after liver transplant did not result in significant differences in long-term outcomes.