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Page 2 of 11 Fatourou et al. Hepatoma Res 2018;4:63 I http://dx.doi.org/10.20517/2394-5079.2018.62

Figure 1. The predictive role of AFP pre- and post-LT. AFP: alpha-fetoprotein; HCC: hepatocellular carcinoma; LT: liver transplantation

[3]
with HCC still develop HCC recurrence post-LT . It is also apparent that factors beyond tumour size and
number are associated with more aggressive tumour biology and are accountable for increasing the risk of
[4]
HCC recurrence . Among these, alpha-fetoprotein (AFP) has been increasingly recognised as a valuable
marker in predicting HCC recurrence [Figure 1] . Although an association between high AFP values and
[5]
[6]
poor outcomes post LT has been established , it has still not been incorporated in the most widely used listing
criteria. Several scoring systems encompassing pre-LT serum AFP levels and tumour size criteria have been
recently proposed and have shown to have better predictability of recurrence compared to traditional Milan
criteria [7-10] .

The aim of this review is to summarise the emerging evidence on the role of AFP as a predictor of HCC
recurrence following LT, either as an independent value or after being combined with tumour size criteria into
prognostic models. For this purpose, an electronic PubMed literature search was performed from January
2004 to April 2018 by using the following keywords: “alpha-fetoprotein”, “hepatocellular carcinoma”, “liver
transplantation”, “recurrence” and “survival”. In this review, we have included all the original studies that
evaluated the role of alpha-fetoprotein (AFP) or AFP including models as a predictive marker of prognosis
following LT.

AFP AS AN INDEPENDENT PREDICTOR OF RECURRENCE AND SURVIVAL
Several studies have been published with regard to an AFP absolute cut-off value or AFP change on the waiting
[14]
list, as an independent predictor of prognosis [5,9,11-13] . In a meta-analysis that included 13 studies , the upper
cut-off AFP value varied widely between 20 ng/mL and 1000 ng/mL. Due to this variation between different
studies, this meta-analysis was unable to suggest a single cut-off level which could be universally approved
across centres. Despite that, a significant correlation between AFP and both post-transplant recurrence and
[14]
prognosis was established in the majority of the reported studies .
The critical question as to whether downstaging HCC patients with high AFP is feasible and is associated with