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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2016; 22(34): 7676-7691
Published online Sep 14, 2016. doi: 10.3748/wjg.v22.i34.7676
Tolerance in liver transplantation: Biomarkers and clinical relevance
Alberto Baroja-Mazo, Beatriz Revilla-Nuin, Pascual Parrilla, Laura Martínez-Alarcón, Pablo Ramírez, José Antonio Pons
Alberto Baroja-Mazo, Beatriz Revilla-Nuin, Pablo Ramírez, José Antonio Pons, Pacual Parrilla, Laura Martínez-Alarcon, Biomedical Research Institute of Murcia (IMIB-Arrixaca-UMU), 30120 Murcia, Spain
Pascual Parrilla, Pablo Ramírez, José Antonio Pons, Division of Gastroenterology and Hepatology and Liver Transplant Unit, University Hospital Virgen de la Arrixaca, 30120 Murcia, Spain
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Supported by the Fondo de Investigaciones Sanitarias Grants, No. PI12/02042.
Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: José Antonio Pons, MD, PhD, Division of Gastroenterology and Hepatology and Liver Transplant Unit, University Hospital Virgen de la Arrixaca, Ctra. Madrid-Cartagena, s/n, 30120 Murcia, Spain. joseapons.imib.arrixaca@gmail.com
Telephone: +34-968-369500 Fax: +34-968-369776
Received: April 28, 2016
Peer-review started: May 1, 2016
First decision: June 20, 2016
Revised: July 4, 2016
Accepted: August 5, 2016
Article in press: August 5, 2016
Published online: September 14, 2016
Processing time: 132 Days and 12.1 Hours
Abstract

Transplantation is the optimal treatment for end-stage organ failure, and modern immunosuppression has allowed important progress in short-term outcomes. However, immunosuppression poorly influences chronic rejection and elicits chronic toxicity in current clinical practice. Thus, a major goal in transplantation is to understand and induce tolerance. It is well established that human regulatory T cells expressing the transcription factor FoxP3 play important roles in the maintenance of immunological self-tolerance and immune homeostasis. The major regulatory T cell subsets and mechanisms of expansion that are critical for induction and long-term maintenance of graft tolerance and survival are being actively investigated. Likewise, other immune cells, such as dendritic cells, monocyte/macrophages or natural killer cells, have been described as part of the process known as “operational tolerance”. However, translation of these results towards clinical practice needs solid tools to identify accurately and reliably patients who are going to be tolerant. In this way, a plethora of genetic and cellular biomarkers is raising and being validated worldwide in large multi-center clinical trials. Few of the studies performed so far have provided a detailed analysis of the impact of immunosuppression withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with them. The future of liver transplantation is aimed to develop new therapies which increase the actual low tolerant vs non-tolerant recipients ratio.

Keywords: Liver transplantation; Operational tolerance; Regulatory T cells; Dendritic cells; Biomarkers

Core tip: Nowadays, the major goal in transplantation is to understand and induce tolerance. Although a plethora of genetic and cellular biomarkers is raising and being validated worldwide in large multi-center clinical trials, little is known about the impact of immunosuppression withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with them. The future of liver transplantation is aimed to develop new therapies which increase the actual low tolerant vs non-tolerant recipients ratio.