Evaluation of the AFP Model in Predicting Recurrence of Hepatocellular Carcinoma After Liver Transplantation in Patients Without Microvascular Invasion.

Introduction Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is a catastrophic event, with limited therapeutics and poor survival [1]. Prior to 1990s, transplantation for HCC was a limited option with high recurrence and poor recipient survival, largely because of a lack of accurate selection of transplant candidates and a late diagnosis.

The Milan criteria have remained as the gold standard selection criteria, with post-transplant 5-year recurrence less than 15% and 5-year survival over 70% [2]. These criteria do not contemplate a relevant histological variable and a risk marker of recurrence, microvascular invasion (mvi). Presence of mvi in the explanted liver has been identified as an independent variable related to recurrence that categorizes patients with low and high risk of HCC recurrence [3]. That is why other selection criteria, beyond Milan criteria, have tried to find pre-transplant surrogate markers of mvi or other related risk factors for recurrence [4-6].

Serum alpha-fetoprotein (AFP) is a marker of renewed interest as a selection criterion, which has been identified as an independent risk variable associated with recurrence and as a surrogate marker of mvi [4,5,7,8]. Evaluation of mvi before LT by a tumor biopsy has many caveats; on the one hand, the risk of tumor seeding, bleeding and other complications and on the other hand, the absence of it does not exclude of its presence in the explanted liver analysis.

Consequently, while it is known that the presence of mvi defines a greater risk, its absence generates uncertainty regarding the risk of recurrence in this population. The Up-to 7 criteria showed that the occurrence of mvi at any size and tumor number was paralleled by a significant lower patient survival and higher recurrence [3]. However, the Metroticket calculator excluded important pre transplant variables such as serum AFP and tumor treatment or progression while on the waitlist [9]. A recently predicting model, the RETREAT score, showed that when considering pre and post transplant variables, the AFP at different cut-offs, presence of mvi and the sum of the largest tumor diameter and tumor number were associated with HCC recurrence [7]. While it has been published earlier in Italian and French cohorts that the prevalence of mvi is 24% [4,11], in another Latin American validation cohort of the AFP model the prevalence of mvi was 22.2% [10].

Our objective therefore, is to evaluate the AFP model against Milan and San Francisco criteria (UCSF) in the prediction of HCC recurrence and patient survival specifically in patients without mvi in the explanted liver and evaluate if the AFP model can assure and identify good candidates for LT that are beyond Milan and UCSF in this subgroup of patients.