Shadows Behind Using Simple Risk Models in Selection of Hepatocellular Carcinoma Patients for Liver Transplantation

To assess the potential influence of replacing Milan criteria with simple risk scores on outcomes of hepatocellular carcinoma (HCC) patients undergoing liver transplantation.

Several risk scores combining morphological and biological features were recently proposed for precise selection of HCC patients for transplantation.

This retrospective study included 282 HCC liver transplant recipients. Recurrence-free survival (RFS), the primary outcome measure, was evaluated according to Metroticket 2.0 model and French AFP model with Milan criteria serving as benchmark.

Patients were well stratified with respect to RFS by Milan criteria, Metroticket 2.0 criteria, and AFP model cut-off ≤2 points (all P < 0.001) with c-statistics of 0.680, 0.695, and 0.681, respectively. Neither Metroticket 2.0 criteria (0.014, Z = 0.023; P = 0.509) nor AFP model (-0.014, Z = -0.021; P = 0.492) provided significant net reclassification improvement. Both patients within the Metroticket 2.0 criteria and AFP model ≤2 points exhibited heterogeneous recurrence risk, dependent upon alpha-fetoprotein (P = 0.026) and tumor number (P = 0.024), respectively. RFS of patients beyond Milan but within Metroticket 2.0 criteria (75.3%) or with AFP model ≤2 points (74.1%) was inferior to that observed for patients within Milan criteria (87.1%; P = 0.067 and P = 0.045, respectively). Corresponding microvascular invasion rates were 37.2% and 50.0%, compared with 13.6% in patients within Milan criteria (both P < 0.001). Moreover, Milan-out status was associated with significantly higher recurrence risk in subgroups within Metroticket 2.0 criteria (P = 0.021) or AFP model ≤2 points (P = 0.014).

Utilization of simple risk scores for liver transplant eligibility assessment leads to selection of patients at higher risk of posttransplant HCC recurrence.