Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 8, 2016; 8(1): 58-68
Published online Jan 8, 2016. doi: 10.4254/wjh.v8.i1.58
Selection of patients with hepatocellular carcinoma for liver transplantation: Past and future
Arturo Soriano, Aranzazu Varona, Rajesh Gianchandani, Modesto Enrique Moneva, Javier Arranz, Antonio Gonzalez, Manuel Barrera
Arturo Soriano, Aranzazu Varona, Rajesh Gianchandani, Modesto Enrique Moneva, Javier Arranz, Antonio Gonzalez, Manuel Barrera, Liver Transplantation Unit, University Hospital Nuestra Señora de Candelaria, Santa Cruz, 38010 Santa Cruz de Tenerife, Spain
Author contributions: Soriano A and Barrera M designed the research; Varona A, Moneva ME, Arranz J and Gonzalez A performed the research; Soriano A and Gianchandani R wrote the paper; Soriano A, Varona A, Gianchandani R, Moneva ME, Arranz J, Gonzalez A and Barrera M reviewed the article and provided final approval.
Conflict-of-interest statement: The authors declare no conflicts 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:
Correspondence to: Manuel Barrera, MD, Chief, Liver Transplantation Unit, University Hospital Nuestra Señora de Candelaria, Santa Cruz, Ctra del Rosario n 145, 38010 Santa Cruz de Tenerife, Spain.
Telephone: +34-92-2602075 Fax: +34-92-2602075
Received: April 29, 2015
Peer-review started: May 8, 2015
First decision: October 21, 2015
Revised: November 18, 2015
Accepted: December 8, 2015
Article in press: December 11, 2015
Published online: January 8, 2016

The aim of liver transplantation (LT) for hepatocellular carcinoma (HCC) is to ensure a rate of disease-free survival similar to that of patients transplanted due to benign disease. Therefore, we are forced to adopt strict criteria when selecting candidates for LT and prioritizing patients on the waiting list (WL), to have clarified indications for bridging therapy for groups at risk for progression or recurrence, and to establish certain limits for downstaging therapies. Although the Milan criteria (MC) remain the standard and most employed criteria for indication of HCC patients for LT by far, in the coming years, criteria will be consolidated that take into account not only data regarding the size/volume and number of tumors but also their biology. This criteria will mainly include the alpha fetoprotein (AFP) values and, in view of their wide variability, any of the published logarithmic models for the selection of candidates for LT. Bridging therapy is necessary for HCC patients on the WL who meet the MC and have the possibility of experiencing a delay for LT greater than 6 mo or any of the known risk factors for recurrence. It is difficult to define single AFP values that would indicate bridging therapy (200, 300 or 400 ng/mL); therefore, it is preferable to rely on the criteria of a French AFP model score > 2. Other single indications for bridging therapy include a tumor diameter greater than 3 cm, more than one tumor, and having an AFP slope greater than 15 ng/mL per month or > 50 ng/mL for three months during strict monitoring while on the WL. When considering the inclusion of patients on the WL who do not meet the MC, it is mandatory to determine their eligibility for downstaging therapy prior to inclusion. The upper limit for this therapy could be one lesion up to 8 cm, 2-3 lesions with a total tumor diameter up to 8 cm, or a total tumor volume of 115 cm3. Lastly, liver allocation and the prioritization of patients with HCC on the WL should take into account the recently described HCC model for end-stage liver disease, which considers hepatic function, HCC size and the number and the log of AFP values. This formula has been calibrated with the survival data of non-HCC patients and produces a dynamic and more accurate assessment model.

Keywords: Hepatocarcinoma, Liver transplantation, Alpha fetoprotein, Patient selection, Prioritization, Waiting list, Bridging therapy, Allocation, Downstaging

Core tip: This article aims to provide clinicians who treat patients with hepatocellular carcinoma, in whom liver transplantation may be indicated, with an actualized tool that considers a combination of morphological (size and number of tumors) and biological data (alpha fetoprotein value) and that facilitates the process of selecting candidates, predicts the indication of and response to neoadjuvant therapy prior to transplantation and also aids in the prioritization of patients once they are on the waiting list.