Prognostic importance of fucosylated alpha-fetoprotein in hepatocellular carcinoma patients with low alpha-fetoprotein

Background and Aim: Fucosylated alpha-fetoprotein (AFP-L3) is known to be a marker of poor prognosis in patients with hepatocellular carcinoma (HCC). However, it has been difficult to measure AFP-L3 under low AFP (≤20ng/mL). The aim of this study was to elucidate the role of AFP-L3 in HCC patients with low AFP conditions. Methods: One hundred and ninety six consecutive newly developed HCC patients with low AFP (≤20ng/mL) were examined for serum AFP-L3 expression by a newly-developed micro-total analysis system that could stably measure AFP-L3 in low AFP circumstances, and its clinical importance was analyzed. Results: Positivity of AFP-L3 in HCC patients was 13.3% at a cut-off level of 10%. Five-year survivals of HCC patients with AFP-L3 (<10%) and AFP-L3 (≥10%) were 69.4% and 41.1%, respectively (P=0.001). Among 18 clinical parameters, low alanine aminotransferase, large tumor size, presence of portal vein tumor thrombus, high AFP and high des-gamma carboxy prothrombin were observed in the high AFP-L3 (≥10%) group. Multivariate analysis revealed that high aspartate aminotransferase (AST) (risk ratio [RR]=3.24, 95% confidence interval [CI]=1.27-8.26), the presence of ascites (RR=3.44, 95% CI=1.22-9.34), multiple tumor number (RR=3.06, 95% CI=1.33-7.17), and high AFP-L3 (RR=8.36, 95% CI=2.79-25.5) were risk factors for survival. High AFP-L3 was also a risk factor for survival in HCC patients who received radiofrequency ablation (P=0.048). Conclusions: AFP-L3 is a strong prognostic factor for survival even in HCC patients with low AFP (≤20ng/mL).