Alpha-fetoprotein Slope >7.5 ng/ml/month Predicts Micro-vascular Invasion and Tumor Recurrence after Liver Transplantation for Hepatocellular Carcinoma.

Background: Rising alpha-fetoprotein (AFP) is a potential marker of worse prognosis after liver transplant (LT) for hepatocellular carcinoma (HCC), but prior studies relied on only two data points and were imprecise in assessing AFP slope. The aim of this study was to examine the association between AFP slope and post-LT HCC recurrence, with AFP slope estimated from multiple data points over time. Methods: Our cohort included 336 patients undergoing LT with MELD exception for HCC within Milan criteria from 2003-2013. Most (98%) had pre-LT loco-regional therapy (LRT). AFP slope was estimated by fitting a regression line to the AFP levels over time. Results: The 1- and 5-year post-LT survival was 94% and 77% and 1- and 5-year recurrence-free probabilities were 95% and 86%, respectively. In univariate analysis, HCC recurrence was significantly associated with microvascular invasion (HR 13.1, pMilan criteria (HR 8.9, p7.5 ng/mL/month (HR 3.9, p=0.005), and female gender (HR 2.3, p=0.01). In multivariable analysis of factors known prior to LT, 3 tumor nodules (HR 7.6, p7.5 (HR 3.0, p=0.03) were significantly associated with HCC recurrence. AFP slope >7.5 was also associated with microvascular invasion (OR 6.8, p=0.008). Conclusions: AFP slope increasing >7.5 ng/mL/month despite LRT is associated with post-LT HCC recurrence and may serve as a surrogate for microvascular invasion. These findings support incorporating changes in the AFP into candidate selection for LT. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

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