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Alpha-Fetoprotein Slope >7.5 ng/mL per Month Predicts Microvascular Invasion and Tumor Recurrence After Liver Transplantation for Hepatocellular Carcinoma

Giard, Jeanne-Marie, MD, MPH1; Mehta, Neil, MD1; Dodge, Jennifer, L., MPH2; Roberts, John, P., MD2; Yao, Francis, Y., MD1,2

doi: 10.1097/TP.0000000000002094
Original Clinical Science—Liver

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 2 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 Model for End Stage Liver Disease exception for HCC within Milan criteria from 2003 to 2013. Most (98%) had pre-LT locoregional therapy. AFP slope was estimated by fitting a regression line to the AFP levels over time.

Results The 1- and 5-year post-LT survivals were 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 (hazard ratio [HR], 13.1; P<0.001), tumor grade (HR, 1.8; P<0.001), pathologic stage >Milan criteria (HR, 8.9; P<0.001), 3 tumor nodules (HR, 5.5; P=0.002), AFP slope greater than 7.5 ng/mL per month (HR, 3.9; P=0.005), and female sex (HR, 2.3; P=0.01). In multivariable analysis of factors known before LT, 3 tumor nodules (HR, 7.6; P<0.001), female sex (HR, 2.5; P=0.01), and AFP slope >7.5 (HR, 3.0; P=0.03) were significantly associated with HCC recurrence. AFP slope greater than 7.5 was also associated with microvascular invasion (odds ratio, 6.8; P=0.008).

Conclusions AFP slope increasing greater than 7.5 ng/mL per month despite locoregional therapy 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.

Optimizing the prediction of HCC recurrence, and therefore the allocation of organs to ensure the best outcomes, remains a work in progress. The authors demonstrate the use of AFP as a dynamic marker for improved prediction of biologic risk to complement the morphologic criteria in HCC candidate selection.

1 Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA.

2 Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA.

Received 16 June 2017. Revision received 8 November 2017.

Accepted 2 December 2017.

The authors declare no funding or conflicts of interest.

Current address for J.-M.G.D.: Division of Hepatology, Department of Medicine, Hôpital Saint-Luc, Université de Montréal, 1058 Saint-Denis, Montréal, Quebec, Canada H2X 3J4.

J.-M.G. participated in research design, performance of the research, data analysis, and writing of the article. N.M. participated in research design, performance of the research, data analysis, participated in the writing of the article. J.L.D. participated in research design, participated in data analysis, participated in the writing of the article. J.P.R. participated in the writing of the article. F.Y.Y. participated in research design, participated in the performance of the research, participated in data analysis, participated in the writing of the article.

Correspondence: Francis Y. Yao, MD, University of California, San Francisco, Rm S-357, 513 Parnassus Ave, San Francisco, CA 94143-0538. (francis.yao@ucsf.edu).

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