Liver transplantation for hepatocellular carcinoma (HCC) has come a long way since the early days of high recurrence rates and the questions over whether liver transplantation

Transl Gastroenterol Hepatol 2019;4:1 tgh.amegroups. com Liver transplantation for hepatocellular carcinoma (HCC) has come a long way since the early days of high recurrence rates and the questions over whether liver transplantation should really be used for treating malignancy (1,2). Transplantation is now firmly established as a curative option for a select group of pat ients with HCC. Unfortunately, we still deny many patients with this cancer the option of transplantation because of adherence to old patient selection criteria that excludes many on grounds of inadequate survival benefit when comparing to non-HCC indications for liver transplantation. The early concerns of unacceptably high recurrence rates were overcome by the landmark study by Mazzaferro et al., published in 1996, which provided criteria based on tumor size and number that achieved excellent long-term recurrence-free survival (RFS) (3). This has repeatedly been validated. These criteria referred to as the Milan Criteria (MC) achieved over 70% 5-year survival when adhered to and were therefore globally adopted (4,5). However, this score was based on analysis of the best available data at that time. There has since been a great deal more experience and knowledge gained in this field of practice. This has led to a better understanding of the role of biology as well as tumor bulk in RFS after transplantation. These insights are leading to refinement of criteria for liver transplantation to allow expansion of application of transplantation without compromising outcomes. The University of California, San Francisco (UCSF) criteria have demonstrated that criteria based on pre-operative imaging can be expanded with outcomes comparable to the MC (6-8). Anyone involved with the follow-up care of patients who are transplanted for HCC will know that there are patients with small tumors within the MC who develop recurrence and patients with larger tumors on the limit of, or beyond, accepted radiological criteria who are cured by transplantation. It is therefore widely accepted that we need to better understand the complex tumor biology of HCC and to incorporate available markers for this into our algorithms. The most widely incorporated biological marker is α-fetoprotein (AFP). An AFP >1,000 ng/mL is associated with reduced survival (7). Duvoux et al. proposed a model in 2012 that incorporated AFP and demonstrated AFP predicted tumor recurrence. The model included tumor size, number of tumors and AFP, and a score greater than 2 was predictive of increased 5-year recurrence 50.6% vs. 8.8% for a score of 2 or less (9). AFP now widely features in the listing criteria for many liver transplant centers but not all, and in those that employ AFP there is variability in cut-offs (9-12). It is also important to note the use of loco-regional therapy as a bridge to transplant is becoming standard practice. Additionally, downstaging is increasingly accepted for patients who would otherwise be ineligible for liver transplant based on the size and number of tumors and in some cases AFP. This adds another level of complexity to the field and how we incorporate AFP in this cohort of patients. Both the European Association for the Study of Liver Diseases (EASL) and the American Association for Editorial