High tacrolimus intra-patient variability is associated with graft rejection, and de novo donor-specific antibodies occurrence after liver transplantation

doi:10.3748/wjg.v24.i16.1795

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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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.

Correspondence to: Arnaud Del Bello, MD, Doctor, Department of Nephrology and Organ Transplantation, CHU Rangueil, TSA 50032, Cedex 9, Toulouse 31059, France. delbello.a@chu-toulouse.fr

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
Processing time: 142 Days and 12.1 Hours

Abstract

AIM

To investigate the role of tacrolimus intra-patient variability (IPV) in adult liver-transplant recipients.

METHODS

We retrospectively assessed tacrolimus variability in a cohort of liver-transplant recipients and analyzed its effect on the occurrence of graft rejection and de novo donor-specific antibodies (dnDSAs), as well as graft survival during the first 2 years posttransplantation. Between 02/08 and 06/2015, 116 patients that received tacrolimus plus mycophenolate mofetil (with or without steroids) were included.

RESULTS

Twenty-two patients (18.5%) experienced at least one acute-rejection episode (BPAR). Predictive factors for a BPAR were a tacrolimus IPV of > 35% [OR = 3.07 95%CI (1.14-8.24), P = 0.03] or > 40% [OR = 4.16 (1.38-12.50), P = 0.01), and a tacrolimus trough level of < 5 ng/mL [OR=3.68 (1.3-10.4), P =0.014]. Thirteen patients (11.2%) developed at least one dnDSA during the follow-up. Tacrolimus IPV [coded as a continuous variable: OR = 1.1, 95%CI (1.0-1.12), P = 0.006] of > 35% [OR = 4.83, 95%CI (1.39-16.72), P = 0.01] and > 40% [OR = 9.73, 95%CI (2.65-35.76), P = 0.001] were identified as predictors to detect dnDSAs. IPV did not impact on patient- or graft-survival rates during the follow-up.

CONCLUSION

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

Keywords: Variability; Liver transplantation; Donor-specific antibodies; Immunosuppression

Core tip: Tacrolimus intra-patient variability (Tac IPV) was associated with kidney-graft rejection and worse long-term outcomes, but until now, was not well studied after liver transplantation in adult recipients. We found that the coefficient of variability-IPV of tacrolimus was a predictive factor for acute rejection and the occurrence of de novo donor-specific antibodies (DSA) after liver transplantation in a retrospective cohort of 116 recipients treated with tacrolimus and mycophenolate mofetil. This 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.