Alpha-fetoprotein dynamics in the waiting list as a biomarker of hepatocellular carcinoma recurrence and mortality after liver transplant

Abstract

Introduction: There is a lack of information on the impact that serum alpha-fetoprotein(AFP)dynamics may have on hepatocellular carcinoma(HCC)recurrence and survival after liver transplantation(LT).We aimed to assess if this could serve as a surrogate of tumor biology. Methods: We assessed all patients who underwent LT for HCC between January 2004 and December 2014.Only patients with a measurement of serum AFP at listing and at LT were included.AFP ratio was defined as AFP at LT/AFP at listing.Patients with more than 2-times increase in AFP were compared to those with less than 2-times increase and those with a decrease or no change in AFP.The primary outcomes were overall survival(OS)and disease-free survival(DFS).Multivariate Cox regression was applied to identify predictors of post-LT outcomes. Results: 506 patients were transplanted for HCC;442 patients were included in the study.There were 292 patients(66.1%)with a decrease or no change in AFP(Group1),86(19.4%)with an increase< double(Group2)and 64(14.5%)with a double increase(Group3). These 3 groups were comparable.The 5-years DFS was 71.3%for Group1 vs 66.4%for Group2 and 52.2%for Group3,p=0.018.The 5-years OS was 75.7% for Group1 vs 72.9%for Group2 vs. 54.3% for Group3,p=0.03. The sole risk factors for recurrence after adjusting for confounders were double increase in the AFP ratio[HR2.4(1.4-4.1),p=0.001]and maximum tumor size at listing[HR1.12(1.06-1.19),p< 0.001];however the only risk factor for death was a double increase in AFP[HR1.60(1.04-2.4),p=0.001]after adjusting for confounders. Conclusion: Double increase in the serum AFP while patients are waiting for LT is a strong predictor of outcomes. This dynamic serum AFP biomarker may serve to expand the“size and number criteria” without impairing the results of LT.Tabled 1FP16-01 Table [Patient characteristics]AFP RatioN (442)Group 1 ≤ (292, 66.1%)Group 2 1-2 (86, 19.4%)Group 3 ≥ (64, 14.5%)p valueAge, y*58 (53-62)58 (53-62)58 (52-62)57 (50-61)0.661Male, %369 (83.5)243 (83.2)75 (87.2)51 (79.7)0.461Bridging therapy, %329 (74.4)227 (77.7)58 (67.4)44 (68.8)0.083 Radiofrequency ablation, %208 (63.2)150 (66.1)31 (53.4)27 (61.4)0.197 Transarterial79 (24.0)51 (22.5)15 (25.9)23 (52.3)0.001chemoembolization, %MELD at listing*10 (8-14)10 (8-13)10 (8-13)11 (9-14)0.654Waiting time (months)*6 (2-11)6 (2-11)6 (2-11)6 (3-12)0.651Listing max. tumor size, cm*2.5 (1.5-3.9)2.5 (1.5-3.9)2.5 (1.4-3.9)2.5 (1.5-3.9)0.835PreLT max. tumor size, cm*2.0 (0.0-3.2)1.8 (0-3.0)1.8 (0-3.3)2.4 (1.3-3.4)0.106Listing tumor number*1 (1-2)1 (1-2)1 (1-2)1 (1-3)0.292PreLT tumor number*1 (0-2)1 (0-2)1 (0-2)2 (1-3)0.028Listing AFP*13 (5-47)11 (5-47)18 (7-50)21 (9-63)0.196PreLT AFP*11 (5-44)7 (5-16)20 (9-63)76 (27-522)<0.001AFP difference*0 (-5-3)-2 (-14-0)4 (2-13)59 (18-426)<0.001*median (IQR)Abbreviation: BMI: Body mass index; MELD: Model for End-Stage Liver Disease; AFP: alpha-fetoprotein: Open table in a new tab *median (IQR) Abbreviation: BMI: Body mass index; MELD: Model for End-Stage Liver Disease; AFP: alpha-fetoprotein: