BACKGROUND & AIMS: Outcomes of liver transplantation for hepatocellular 
carcinoma (HCC) are determined by cancer-related and non-related events. 
Treatments for hepatitis C virus infection have reduced non-cancer events among 
patients receiving liver transplants, so reducing HCC-related death might be an 
actionable end point. We performed a competing-risk analysis to evaluate factors 
associated with survival of patients with HCC and developed a prognostic model 
based on features of HCC patients before liver transplantation.
METHODS: We performed multivariable competing-risk regression analysis to 
identify factors associated with HCC-specific death of patients who underwent 
liver transplantation. The training set comprised 1018 patients who underwent 
liver transplantation for HCC from January 2000 through December 2013 at 3 
tertiary centers in Italy. The validation set comprised 341 consecutive patients 
who underwent liver transplantation for HCC during the same period at the Liver 
Cancer Institute in Shanghai, China. We collected pretransplantation data on 
etiology of liver disease, number and size of tumors, patient level of 
α-fetoprotein (AFP), model for end-stage liver disease score, tumor stage, 
numbers and types of treatment, response to treatments, tumor grade, 
microvascular invasion, dates, and causes of death. Death was defined as 
HCC-specific when related to HCC recurrence after transplantation, disseminated 
extra- and/or intrahepatic tumor relapse and worsened liver function in presence 
of tumor spread. The cumulative incidence of death was segregated for hepatitis 
C virus status.
RESULTS: In the competing-risk regression, the sum of tumor number and size and 
of log10 level of AFP were significantly associated with HCC-specific death (P < 
.001), returning an average c-statistic of 0.780 (95% confidence interval, 
0.763-0.798). Five-year cumulative incidence of non-HCC-related death was 8.6% 
in HCV-negative patients and 18.1% in HCV-positive patients. For patients with 
HCC to have a 70% chance of HCC-specific survival 5 years after transplantation, 
their level of AFP should be <200 ng/mL and the sum of number and size of tumors 
(in centimeters) should not exceed 7; if the level of AFP was 200-400 ng/mL, the 
sum of the number and size of tumors should be ≤5; if their level of AFP was 
400-1000 ng/mL, the sum of the number and size of tumors should be ≤4. In the 
validation set, the model identified patients who survived 5 years after liver 
transplantation with 0.721 accuracy (95% confidence interval, 0.648%-0.793%). 
Our model, based on patients' level of AFP and HCC number and size, outperformed 
the Milan; University of California, San Francisco; Shanghai-Fudan; Up-to-7 
criteria (P < .001); and AFP French model (P = .044) to predict which patients 
will survive for 5 years after liver transplantation.
CONCLUSIONS: We developed a model based on level of AFP, tumor size, and tumor 
number, to determine risk of death from HCC-related factors after liver 
transplantation. This model might be used to select end points and refine 
selection criteria for liver transplantation for patients with HCC. To predict 
5-year survival and risk of HCC-related death using an online calculator, please 
see www.hcc-olt-metroticket.org/. ClinicalTrials.gov ID NCT02898415.