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Page 8 of 11 Fatourou et al. Hepatoma Res 2018;4:63 I http://dx.doi.org/10.20517/2394-5079.2018.62

TRAIN score
[30]
In a study by Lai et al. , a prognostic score that included radiological response criteria (mRESIST), AFP slope,
neutrophil to lymphocyte ratio (NLR) prior to transplantation and waiting time (WT) on the transplant list
was developed following retrospective analysis of a single cohort (n = 179). The Time-radiological response-
AFP-Inflammation (TRAIN) score is calculated as shown in the equation; 0.988 (if mRESIST-progressive
disease) + 0.838 (if AFP slope ≥ 15 ng/mL/month) + 0.452 (if NLR ≥ 5.0)-0.03*WT9 (x month). A Score ≥ 1
has shown an excellent ability to stratify patient in terms of intention to treat survival and recurrence. The
TRAIN score allowed a potential 8.9% increase in the patients eligible for transplantation without increasing
the recurrence risk that would have otherwise been excluded based on the Milan criteria. One of the main
disadvantages of this proposed score is that it can only be applied in patients who have undergone pre-
transplant locoregional treatment.

THE PROGNOSTIC ROLE OF AFP IN THE CONTEXT OF LT AS REPORTED IN NATIONAL AND
INTERNATIONAL GUIDELINES
Despite the emerging robust evidence on the ability of pre-operative AFP to predict pre-transplant recurrence,
only few International transplant societies have implemented this as part of their listing criteria.

The recently revised EASL Clinical Practice guidelines recommend that the conservative Milan criteria are the
[2]
benchmark for selection of patients with HCC for LT . Despite this, it is suggested that composite criteria that
consider surrogates of tumour biology, (among which AFP is the most relevant), in combination with tumour
size and number of nodules is likely to replace conventional criteria for defining eligibility for LT. Although,
different cut-off levels have been proposed (100 ng/mL, 200 ng/mL, 400 ng/mL, 1000 ng/mL) no consensus has
been reached as to the optimal cut-off level that would best predict HCC recurrence.

In the UK, patients are eligible for LT if they have a single tumour ≤ 5 cm diameter or up to 5 tumours
all ≤ 3 cm or a single tumour > 5 cm and ≤ 7 cm diameter, where there has been no evidence of tumour
progression (volume increase by < 20%), no extra-hepatic spread and no new nodule formation over a 6-month
period. Since 2012, a cut-off AFP level more than 1000 i.u/mL has been used as an exclusion criterion for
listing. Tumour rupture, extra-hepatic spread and macrovascular invasion are also considered as absolute
[31]
contraindications for transplantation .

[10]
In 2013, the French Organization for Organ Sharing officially implemented the AFP model as the national
listing criteria for transplantation. This includes AFP at different cut off levels in combination with tumour size
[10]
and number . A simplified version of the original model has been proposed [Table 2] and has shown to be
[26]
superior to Milan criteria in predicting HCC recurrence. The AFP model has been externally validated and
has been shown to discriminate well between patients with low and high risk of recurrence, both in patients
within or beyond Milan criteria.

In 2008, the Canadian Society for Transplantation recommended that programs use a combination of total tu-
[9]
mour volume (TTV), and AFP as listing criteria . Patients are eligible for transplantation if they have TTV ≤
3
115 cm and AFP ≤ 400 ng/mL. Unlike the Milan criteria, the current score allows the eligibility of patients
with more than three tumours but with low tumour volume, which has been associated with favourable out-
3
[9]
comes . The TTV is calculated as the sum of the volume of each tumour [(4/3)πr ] based on the maximum
radius of each tumour.

Finally, the international consensus conference on LT for HCC which was held in Zurich in 2010 and
established internationally accepted statements and guidelines for the conduct of LT, suggested that AFP
should be utilised for waiting-list monitoring and following bridging therapy to discriminate between patients
[32]
with low and high risk for drop out .