High-sensitivity Lens culinaris agglutinin-reactive alpha-fetoprotein assay predicts early detection of hepatocellular carcinoma

Abstract

BackgroundPrognosis of patients with hepatocellular carcinoma (HCC) remains poor because HCC is frequently diagnosed late. Therefore, regular surveillance has been recommended to detect HCC at the early stage when curative treatments can be applied. HCC biomarkers, including Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), are widely used for surveillance in Japan. A newly developed immunoassay system measures AFP-L3 % with high sensitivity. This retrospective study aimed to evaluate clinical utility of high-sensitivity AFP-L3 (hs-AFP-L3) as a predictor of early stage HCC in surveillance at a single site.MethodsOf consecutive 2830 patients in the surveillance between 2000 and 2009, 104 HCC-developed and 104 non-HCC patients were selected by eligibility criteria and propensity score matching. Samples were obtained from the HCC patients who had blood drawn annually for 3 years prior to HCC diagnosis.ResultsIn the present study, hs-AFP-L3 was elevated 1 year prior to diagnosis in 34.3 % of patients. The survival rate of patients with the hs-AFP-L3 ≥ 7 % at 1 year prior to diagnosis was significantly lower than that of patients with hs-AFP-L3 < 7 %.ConclusionsElevation of hs-AFP-L3 was early predictive of development of HCC even at low AFP levels and in absence of ultrasound findings of suspicious HCC. The hs-AFP-L3 should be added to surveillance programs with US because elevated hs-AFP-L3 may be a trigger to perform enhanced imaging modalities for confirmation of HCC.

Current biomarkers for hepatocellular carcinoma: Surveillance, diagnosis and prediction of prognosis

“…Numerous studies have investigated the performance of alternative markers or combinations of already established markers. New candidate markers include squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IGM), α-l-fucosidase [29] , glypican-3 (GPC-3), insulin-like growth factor (IGF) [30] , vascular endothelial growth factor (VEGF), or Dickkopf-1 (DKK1) [31] . Three further biomarkers have intensively been studied for their potential use in screening for HCC, namely Golgi protein 73 (GP73), interleukin-6 (IL-6) and squamous cell carcinoma antigen (SCCA) and were addressed in a recent meta-analysis [32] .…”

Functional glycomics: Application to medical science and hepatology

“…In addition, AFP‐L3‐positive HCC showed poor prognosis compared with AFP‐L3‐negative HCC. μTASWako i30 is a diagnostic system that can rapidly measure AFP‐L3 even at very low levels . Quantification of fucosylated AFP levels, but not that of the ratio of AFP‐L3/total AFP, gives some changes in the significance of AFP‐L3 as an early HCC biomarker .…”

Biomarkers for Hepatocellular Carcinoma

“…To address this problem, combined application of DCP- and AFP-based biomarkers has been tested. A novel predictive model comprising AFP-L3, AFP and DCP achieved a sensitivity of 60.6% and specificity of 100% when applied to a cohort of 104 HCC patients, 43% of whom showed AFP levels below 10 ng/mL 27. Meanwhile, a large multicenter case-control study conducted in 201028 suggested that DCP-based diagnostic method coupled with AFP immunoassay for HCC detection resulted in an increase in sensitivity from 65% to 87% at the expense of the specificity score, which dropped from 84% to 69%.…”