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Page 4 of 21 Toniutto et al. Hepatoma Res 2020;6:50 I http://dx.doi.org/10.20517/2394-5079.2020.40

Table 2. The pre-operative models assessing the risk of hepatocellular carcinoma recurrence after liver transplantation.
Only risk models that have been externally validated for use before liver transplantation are presented
Authors - model name Factors included in the model Outcomes after liver transplantation
Mazzaferro et al. [6] Number (up to three identified as < 3 cm in diameter) and 4-year post-LT survival 75%
Milan criteria size (up to 5 cm if single) of nodules 4-year RFS 83%
Fan et al. [21] Number and size of nodules (≤ 9 cm if single, no more than 3 3-years post-LT survival 80%
Fudan-Shanghai criteria lesions with the largest ≤ 5 cm), total tumor diameter ≤ 9 cm 3-years RFS 88%
Yao et al. [23] Number and size of nodules (≤ 6.5 cm if single or 2-3 lesions 5-year RFS 80.7%
San Francisco (UCSF) criteria ≤ 4.5 cm), total tumor diameter ≤ 8 cm
DuBay et al. [51] Tumor confined to the liver, no poor histologic differentiation 5-year post-LT survival 70%
Toronto criteria on biopsy, AFP serum levels < 400 ng/mL 5-year RFS 66%
Toso et al. [55] Total tumor volume ≤ 115 cm and AFP serum levels ≤ 400 4-year post-LT survival 74.6%
3
Toso criteria ng/mL 4-year RFS 68%
Duvoux et al. [43] Size and number of nodules (≤ 3 cm, between 3-6 cm or ≥ 5-year post-LT survival 69.9%
French model 6 cm) and AFP serum levels ≤ 100, between 100-1000, or > 5-year RFS 66.6%
1000 ng/mL
Mazzaferro et al. [59] Number and size of nodules (up-to-seven criteria) and AFP 5-year post-LT survival 74.9%
Metroticket 2.0 serum levels 5-year RFS 77.9%
Zheng et al. [53] HCC ≤ 8 cm or > 8 cm associated with AFP < 400 ng/mL and 5-year post LT survival 70.7%
Hangzhou criteria tumor histological grade I or II 5-years RFS 62.4%
Kaido et al. [68] Up to 10 nodules ≤ 5 cm in diameter and DCP serum levels ≤ 5-year post-LT survival 82%
Kyoto criteria (LDLT) 400 mAU/mL 5-year HCC recurrence rate 4.4%
Lee et al. [71] DCP and AFP serum levels 5-year post-LT survival 86%
MoRAL model (LDLT) 5-year RFS 66.3%
LDLT: living donor liver transplantation; AFP: alpha-fetoprotein; DCP: des-gamma-carboxyprothrombin; RFS: recurrence-free survival

Table 3. The post-operative models to assess the risk of hepatocellular carcinoma recurrence after liver transplantation. In
the table are presented the only risk models that have been externally validated for use after liver transplantation
Authors - model name Factors included in the model Outcomes after liver transplantation
Onaca et al. [113] Single lesion ≤ 6 cm or 2-4 lesions ≤ 5 cm each 5-year post-LT survival 67.8%
5-year RFS 63.9%
Mazzaferro et al. [11] Sum of the size of the largest tumor (in cm) and the number 5-year post-LT survival 71.2%
Up-to-seven Metroticket criteria of tumors not exceeding 7 in the absence of MVI 5-year recurrence rate 9.1%
Decaens et al. [114] Number of nodules, largest tumor diameter, and tumor 5-year RFS 60.2%
differentiation 5-year recurrence rate 20.8%
Halazun et al. [115] Pre LT largest HCC nodule < 3 cm, NLR < 5 and AFP < 200 5-years RFS 80%
Combo-MoRAL score ng/mL plus post LT HCC number < 3, largest nodule < 3 cm,
HCC histological grade < 4 and no MVI
Mehta et al. [116] AFP serum levels at LT, the sum of the largest viable tumor 5-year recurrence rate 12.8%
RETREAT criteria diameter, and number of viable tumors

MVI: microvascular invasion; NLR: neutrophil/lymphocyte ratio; AFP: alpha-fetoprotein; LT: liver transplantation; RFS: recurrence-free
survival

in patients transplanted for HCC due mainly to chronic hepatitis B virus (HBV) infection. The authors
demonstrated that expanding the indications for LT in patients with solitary HCC ≤ 9 cm in diameter,
or with no more than 3 lesions (the largest ≤ 5 cm) with a total tumor diameter of ≤ 9 cm, there was no
significant difference in 1- and 3-year survival and in recurrence-free survival as compared to the Milan
[21]
criteria . The aforementioned Fudan-Shanghai criteria were subsequently validated in seven Shanghai
[22]
liver transplant centers, which included 1,078 patients . The second study was conducted in the US and
gave rise to the University of California San Francisco (UCSF) criteria . These criteria suggested that
[23]
having a single lesion ≤ 6.5 cm or 2-3 lesions ≤ 4.5 cm each, with a total tumor diameter ≤ 8 cm, resulted in
5-years post-LT recurrence-free survival in 80.7% of cases, which was not worse compared to that observed
when applying the Milan criteria.

The most important limitation of morphologic criteria based exclusively on radiological imaging
-performed by contrasted computed tomography (CT) scan or magnetic resonance imaging (MRI) - is
the accuracy in detecting any single lesion in the liver, and, more importantly, to properly characterize it.