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

Abstract

Objective: To assess the potential influence of replacing Milan criteria with simple risk scores on outcomes of hepatocellular carcinoma (HCC) patients undergoing liver transplantation. Summary Background Data: Several risk scores combining morphological and biological features were recently proposed for precise selection of HCC patients for transplantation. Methods: 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. Results: 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). Conclusion: Utilization of simple risk scores for liver transplant eligibility assessment leads to selection of patients at higher risk of posttransplant HCC recurrence.

Pre‐transplant alpha‐fetoprotein is associated with post‐transplant hepatocellular carcinoma recurrence mortality

“…However, the incidence of HCC recurrence after transplantation is high, up to 8%‐20% at five years . Prior literature has identified numerous risk factors for patients at risk of HCC recurrence, including pre‐transplant alpha‐fetoprotein (AFP), shorter time on the waiting list, etiology of liver disease, and pathology characteristics such as microvascular invasion . However, there are limited data on survival among patients who experience HCC recurrence, as well as associated risk factors for mortality.…”

Extremes of Liver Transplantation for Hepatocellular Carcinoma

“…However, obtained results of patients’ survival do not confirm their transplant eligibility, despite having AFP model scores of 2 and less. While patients beyond Milan criteria but with AFP models of up to 2 points were recently shown to be at an increased, yet still acceptable, risk of tumor recurrence, this does not seem to apply to patients with intrahepatic dissemination [27]. Moreover, our outcomes could be a reason to discuss if the AFP model needs an upper limit of tumors in its own classification score.…”

Liver Transplantation for Extended Criteria Hepatocellular Carcinoma Using Stable Response to Locoregional Therapy and Alpha-Fetoprotein as Selection Criteria

“…AFP combined with tumor size and number at one arbitrary time point, however, is probably not enough to define inclusion and exclusion criteria. In a recent study, the authors could not find any net reclassification benefit using the Metroticket 2.0 criteria or the AFP model [23]. The response to therapy to an LRT procedure seems to have good predictive power for the survival of the patients [6, 24].…”