Retrospective Cohort Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2018; 24(16): 1795-1802
Published online Apr 28, 2018. doi: 10.3748/wjg.v24.i16.1795
High tacrolimus intra-patient variability is associated with graft rejection, and de novo donor-specific antibodies occurrence after liver transplantation
Arnaud Del Bello, Nicolas Congy-Jolivet, Marie Danjoux, Fabrice Muscari, Laurence Lavayssière, Laure Esposito, Anne-Laure Hebral, Julie Bellière, Nassim Kamar
Arnaud Del Bello, Laurence Lavayssière, Laure Esposito, Anne-Laure Hebral, Julie Bellière, Nassim Kamar, Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse 31000, France
Arnaud Del Bello, Nicolas Congy-Jolivet, Fabrice Muscari, Julie Bellière, Nassim Kamar, Université Paul Sabatier, Toulouse 31000, France
Nicolas Congy-Jolivet, Department of Immunology, CHU de Toulouse, Hôpital de Rangueil, CHU de Toulouse, Toulouse 31000, France
Marie Danjoux, Department of Pathology, Institut Universitaire du Cancer, CHU Toulouse 31000, France
Fabrice Muscari, Department of Surgery and Liver Transplantation, Toulouse 31000, France
Julie Bellière, Molecular Immunogenetics Laboratory, Faculté de Médecine Purpan, IFR150 (INSERM), Montréal H3G 1Y6, France
Nassim Kamar, INSERM, IFR-BMT, CHU Purpan, Toulouse 31000, France
Author contributions: Del Bello A and Kamar N designed research; Del Bello A, Congy-Jolivet N, Danjoux M, Muscari F, Lavayssière L, Esposito L, Hebral AL, Bellière J and Kamar N followed patients and performed research; Del Bello A, Bellière J, and Kamar N contributed analytic tools; Del Bello A and Kamar N analysed data; Del Bello A and Kamar N wrote the paper.
Institutional review board statement: The study was reviewed and approved for publication by our Institutional Reviewer.
Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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:
Correspondence to: Arnaud Del Bello, MD, Doctor, Department of Nephrology and Organ Transplantation, CHU Rangueil, TSA 50032, Cedex 9, Toulouse 31059, France.
Telephone: +33-5-61323923 Fax: +33-5-61323989
Received: December 5, 2017
Peer-review started: December 5, 2017
First decision: January 18, 2018
Revised: March 6, 2018
Accepted: March 31, 2018
Article in press: March 30, 2018
Published online: April 28, 2018
Research background

Tacrolimus (Tac) is considered a cornerstone within immunosuppression protocols to prevent T-cell and antibody-mediated rejection after liver transplantation. However, this treatment presents a narrow therapeutic index: overexposure can lead to clinically serious events, thus necessitating regular therapeutic drug monitoring, whereas underexposure can lead to acute or chronic graft rejection. The concept of intra-patient variability (IPV) refers to the fluctuations in Tac blood concentrations (and consequently episodes of over- and under-immunosuppression) that some patients experience over time.

Research motivation

Tac-IPV is an inexpensive assay to explore fluctuations in Tac blood concentrations. We investigated the potential usefulness of Tac-IPV to predict the incidence of donor specific antibodies and graft rejection episodes.

Research objectives

Our aim was to investigate the role of tacrolimus IPV in adult liver-transplant recipients.

Research methods

We retrospectively assessed tacrolimus variability and analyzed its effect on the occurrence of graft rejection and de novo donor-specific antibodies.

Research results

Twenty-two patients experienced at least one acute-rejection episode (BPAR). Predictive factors for a BPAR were a tacrolimus IPV of > 35% or > 40%, and a tacrolimus trough level of < 5 ng/mL. Thirteen patients developed at least one dnDSA during the follow-up. Tacrolimus IPV and tacrolimus IPV of > 35%, and > 40% were identified as predictors to detect dnDSAs. IPV did not impact on patient- or graft-survival rates during the follow-up.

Research conclusions

In our study higher Tac-IPV was associated with graft rejection and occurrence of DSAs.

Research perspective

Tacrolimus-IPV could be a useful tool to identify patients with a greater risk of graft rejection and of developing a de novo DSA after liver transplantation.