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World J Gastroenterol. Mar 28, 2016; 22(12): 3325-3334
Published online Mar 28, 2016. doi: 10.3748/wjg.v22.i12.3325
Liver transplantation for hepatocellular carcinoma beyond the Milan criteria: A review
Dong-Wei Xu, Ping Wan, Qiang Xia
Dong-Wei Xu, Ping Wan, Qiang Xia, Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Author contributions: Xu DW and Wan P equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing; and Xia Q coordinated the research and approved the final manuscript for publication.
Supported by the National Natural Science Foundation of China, No. 81472243.
Conflict-of-interest statement: Authors declare no conflict of interest for 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/
Correspondence to: Dr. Qiang Xia, Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Dongfang Road, NO. 1630, Shanghai 200127, China. xiaqiang@shsmu.edu.cn
Telephone: +86-21-68383775 Fax: +86-21-58737232
Received: September 25, 2015
Peer-review started: September 28, 2015
First decision: October 14, 2015
Revised: December 14, 2015
Accepted: January 30, 2016
Article in press: January 30, 2016
Published online: March 28, 2016
Abstract

Liver transplantation (LT) has been accepted as an effective therapy for hepatocellular carcinoma (HCC). The Milan criteria (MC) are widely used across the world to select LT candidates in HCC patients. However, the MC may be too strict because a substantial subset of patients who have HCC exceed the MC and who would benefit from LT may be unnecessarily excluded from the waiting list. In recent years, many extended criteria beyond the MC were raised, which were proved to be able to yield similar outcomes compared with those patients meeting the MC. Because the simple use of tumor size and number was insufficient to indicate HCC biological features and to predict the risk of tumor recurrence, some biological markers such as Alpha-fetoprotein, Des-Gamma-carboxy prothrombin and the neutrophil-to-lymphocyte ratio were useful in selecting LT candidates in HCC patients beyond the MC. For patients with advanced HCC, downstaging therapy is an effective way to reduce the tumor stage to fulfill the MC by using liver-directed therapy such as transarterial chemoembolization, radiofrequency ablation and percutaneous ethanol injection. This article reviews the recent advances in LT for HCC beyond the MC.

Keywords: Liver transplantation, Biological marker, Milan criteria, Hepatocellular carcinoma, Downstaging therapy, Adjuvant treatment

Core tip: The Milan criteria (MC) were widely used in selecting liver transplantation (LT) candidates in hepatocellular carcinoma (HCC) patients. Because a substantial subset of HCC patients exceeding the MC and who would benefit from LT may be unnecessarily excluded from the waiting list, many extended criteria beyond the MC were raised. To predict the risk of tumor recurrence, some biological markers were also useful in HCC patients beyond the MC. Downstaging and adjuvant therapies are effective ways to reduce the tumor stage and the risk of recurrence. This article reviews the recent advances in LT for HCC beyond the MC.