External validation of the French alpha‐fetoprotein model for hepatocellular carcinoma liver transplantation in a recent unicentric cohort – a retrospective study

Abstract

Summary Prognostic models of liver transplantation (LT) for hepatocellular carcinoma (HCC) mainly derive from LT cohorts with numerous hepatitis C virus (HCV) patients. The AFP model, which is currently used in France to select LT candidates, was derived from a cohort of LT performed between 1988 and 2001, including a majority of HCV‐positive recipients. The emergence of new direct‐acting antiviral therapies and subsequent decrease of HCV incidence may change the generalizability of such models. We performed an external validation of the AFP model in a cohort of recipients transplanted between 2005 and 2018. Although multivariable analysis identified all three model’s factors (AFP level, largest tumor size, number of nodules) as predictors of tumor recurrence, the AFP model showed poor discrimination and calibration in the present cohort. This poor performance could be related to significant differences between the derivation and the present cohort in terms of etiology, severity of underlying liver disease, tumor burden and differentiation, and use of neoadjuvant treatments. The present findings suggest that the decline of HCV‐induced HCC among LT candidates may compromise the generalizability of the AFP model in more recent LT cohorts. Further studies are required for updating or building more robust prognostic models.

Liver transplantation for hepatocellular carcinoma: Historical evolution of transplantation criteria

“…Therefore, they showed that the AFP score well above 2 was 5 times more likely to develop recurrence in 5 years. The AFP model was validated by other researchers[ 60 - 64 ] and all reported similar results as Notarpaolo et al [ 60 ].…”

Patient Selection for Downstaging of Hepatocellular Carcinoma Prior to Liver Transplantation—Adjusting the Odds?

“…The additional value of the AFP level to improve patient selection in this context was first shown in the French AFP model, in which the upper limit of size and number could be increased from the MC criteria to ≤6 cm in cases of ≤3 nodules and to ≤3 cm in cases of ≥4 tumor nodules in patients with pre-LT AFP levels ≤100 ng/ml without a significantly increased risk of HCC recurrence ( 33 ). However, validating studies revealed a poor predictive value of this model, also pointing out the importance of the underlying liver disease (e.g., HCV vs. non-HCV) in different cohorts ( 35 ). In view of the fact that HCV is also displaced by NASH in the LT population ( 36 ), this might become extremely relevant, since many of the models are derived from cohorts with high numbers of patients with viral hepatitis.…”