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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2016; 22(1): 232-252
Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.232
Prediction of hepatocellular carcinoma biological behavior in patient selection for liver transplantation
Umberto Cillo, Tommaso Giuliani, Marina Polacco, Luz Maria Herrero Manley, Gino Crivellari, Alessandro Vitale
Umberto Cillo, Tommaso Giuliani, Marina Polacco, Luz Maria Herrero Manley, Alessandro Vitale, Hepatobiliary Surgery and Liver Transplantation Unit, Department of General Surgery and Organ Transplantation, University Hospital of Padua, 35128 Padova, Italy
Gino Crivellari, Unità Operativa di Oncologia Medica, Istituto Oncologico Veneto (IOV) IRCCS, 35128 Padova, Italy
Author contributions: Cillo U designed the research; Giuliani T and Polacco M performed the research; Cillo U, Giuliani T, Polacco M, Herrero Manley LM wrote the paper; Cillo U, Giuliani T, Polacco M, Herrero Manley LM, Crivellari G and Vitale A revised the paper.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
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: Umberto Cillo, MD, FEBS, Hepatobiliary Surgery and Liver Transplantation Unit, Department of General Surgery and Organ Transplantation, University Hospital of Padua, Via 8 Febbraio, 35128 Padova, Italy. cillo@unipd.it
Telephone: +39-49-8211846 Fax: +39-49-8211718
Received: April 30, 2015
Peer-review started: May 8, 2015
First decision: July 14, 2015
Revised: August 14, 2015
Accepted: November 9, 2015
Article in press: November 9, 2015
Published online: January 7, 2016
Abstract

Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma (HCC) patients for liver transplantation (LT). These criteria, which are often inappropriate to express the tumor’s biological behavior and aggressiveness, offer only a static view of the disease burden and are frequently unable to correctly stratify the tumor recurrence risk after LT. Alpha-fetoprotein (AFP) and its progression as well as AFP-mRNA, AFP-L3%, des-γ-carboxyprothrombin, inflammatory markers and other serological tests appear to be correlated with post-transplant outcomes. Several other markers for patient selection including functional imaging studies such as 18F-FDG-PET imaging, histological evaluation of tumor grade, tissue-specific biomarkers, and molecular signatures have been outlined in the literature. HCC growth rate and response to pre-transplant therapies can further contribute to the transplant evaluation process of HCC patients. While AFP, its progression, and HCC response to pre-transplant therapy have already been used as a part of an integrated prognostic model for selecting patients, the utility of other markers in the transplant setting is still under investigation. This article intends to review the data in the literature concerning predictors that could be included in an integrated LT selection model and to evaluate the importance of biological aggressiveness in the evaluation process of these patients.

Keywords: Hepatocellular carcinoma, Liver Alpha-fetoprotein, Transplantation, Biomarkers, Histopathology, Recurrence, Integrated prognostic tool

Core tip: An integrated model predicting post-transplant survival of hepatocellular carcinoma patients after liver transplantation has not yet been defined. Current selection criteria for liver transplantation that do not consider its biological aggressiveness are mainly based on morphological tumor markers that offer only a static view of the tumor. Many biomarkers predicting post-transplant outcome and stratifying those patients who are candidates for liver transplantation are under evaluation. An integrated prognostic model will make it possible to quantify the tumor burden via functional imaging modalities as well as biological markers.