Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2015; 21(4): 1061-1068
Published online Jan 28, 2015. doi: 10.3748/wjg.v21.i4.1061
Markers of acute rejection and graft acceptance in liver transplantation
Giacomo Germani, Kryssia Rodriguez-Castro, Francesco Paolo Russo, Marco Senzolo, Alberto Zanetto, Alberto Ferrarese, Patrizia Burra
Giacomo Germani, Kryssia Rodriguez-Castro, Francesco Paolo Russo, Marco Senzolo, Alberto Zanetto, Alberto Ferrarese, Patrizia Burra, Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 Padua, Italy
Author contributions: Germani G and Rodriguez-Castro K wrote the paper; Zanetto A, Ferrarese A, Senzolo M and Russo FP retrieved articles and analysed data; Burra P revised the paper.
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: Patrizia Burra, MD, PhD, Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, 35128 Padua, Italy. burra@unipd.it
Telephone: +39-49-8212892 Fax: +39-49-8218727
Received: May 29, 2014
Peer-review started: May 30, 2014
First decision: July 21, 2014
Revised: July 28, 2014
Accepted: October 14, 2014
Article in press: October 15, 2014
Published online: January 28, 2015
Processing time: 242 Days and 18.7 Hours
Abstract

The evaluation of the immunosuppression state in liver transplanted patients is crucial for a correct post-transplant management and a major step towards the personalisation of the immunosuppressive therapy. However, current immunological monitoring after liver transplantation relies mainly on clinical judgment and on immunosuppressive drug levels, without a proper assessment of the real suppression of the immunological system. Various markers have been studied in an attempt to identify a specific indicator of graft rejection and graft acceptance after liver transplantation. Considering acute rejection, the most studied markers are pro-inflammatory and immunoregulatory cytokines and other proteins related to inflammation. However there is considerable overlap with other conditions, and only few of them have been validated. Standard liver tests cannot be used as markers of graft rejection due to their low sensitivity and specificity and the weak correlation with the severity of histopathological findings. Several studies have been performed to identify biomarkers of tolerance in liver transplanted patients. Most of them are based on the analysis of peripheral blood samples and on the use of transcriptional profiling techniques. Amongst these, NK cell-related molecules seem to be the most valid marker of graft acceptance, whereas the role CD4+CD25+Foxp3+ T cells has still to be properly defined.

Keywords: Liver transplantation; Acute cellular rejection; Tolerance; Biomarkers

Core tip: This review explores the available data in the literature concerning potential markers of acute cellular rejection and graft acceptance after liver transplantation, as well as their impact on decision-making for clinicians.