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Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 27, 2019; 11(1): 50-64
Published online Jan 27, 2019. doi: 10.4254/wjh.v11.i1.50
Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation
Maria J Citores, Jose L Lucena, Sara de la Fuente, Valentin Cuervas-Mons
Maria J Citores, Department of Internal Medicine, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Majadahonda 28222, Spain
Jose L Lucena, Liver Transplantation Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda 28222, Spain
Jose L Lucena, Department of Surgery, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda 28222, Spain
Sara de la Fuente, Valentin Cuervas-Mons, Department of Internal Medicine, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda 28222, Spain
Valentin Cuervas-Mons, Department of Medicine, Universidad Autónoma de Madrid, Madrid 28029, Spain
Author contributions: All authors contributed equally 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.
Conflict-of-interest statement: All of the authors declare no conflicts of interest related to this article.
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/
Corresponding author: Maria Jesus Citores, BSc, PhD, Research Scientist, Laboratory of Internal Medicine, Hospital Universitario Puerta de Hierro Majadahonda, Joaquin Rodrigo 2, Majadahonda 28222, Madrid, Spain. mariajesus.citores@salud.madrid.org
Telephone: +34-91-1916768 Fax: +34-91-19 6807
Received: September 28, 2018
Peer-review started: September 28, 2018
First decision: October 19, 2018
Revised: November 13, 2018
Accepted: December 5, 2018
Article in press: December 5, 2018
Published online: January 27, 2019
Processing time: 121 Days and 14.4 Hours
Abstract

Liver transplantation (LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma (HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to 85%of 3- to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, des-gamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, can predict the risk for HCC recurrence after transplantation. These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral recurrence after LT.

Keywords: Hepatocellular carcinoma; Liver transplantation; Recurrence; Selection criteria; Prognostic score; Biomarker; Alpha-fetoprotein; Systemic inflammatory marker

Core tip: The Milan criteria for liver transplantation have improved survival of patients with small hepatocellular carcinoma (HCC), but up to 20% of patients still experience HCC recurrence after transplantation. Microvascular invasion and tumors with poor histologic grade of differentiation are the most important risk factors for HCC recurrence, but they are evidenced after surgery on explant pathology examination. Several surrogate pretransplant biomarkers, directly related with tumor biology or systemic inflammation markers conditioning tumor progression, have been suggested to identify, alone or integrated in pretransplant prognostic scores, patients at high risk of HCC recurrence after liver transplantation.