Highly sensitive lens culinaris agglutinin-reactive α-fetoprotein is useful for early detection of hepatocellular carcinoma in patients with chronic liver disease

Abstract

Abstract. The fucosylated fraction of α-fetoprotein (AFP-L3) is a specific marker for hepatocellular carcinoma (HCC). However, conventional AFP-L3% (c-AFP-L3%) has not always been reliable in cases with low serum α-fetoprotein (AFP) levels. In this study, we evaluated the clinical utility of a newly developed assay, highly sensitive AFP-L3% (hs-AFP-L3%). Subjects included 74 patients with benign liver disease (BLD), including chronic hepatitis and cirrhosis, and 94 with HCC. Serum hs-AFP-L3% was significantly higher than c-AFP-L3% in patients with early-stage HCC (solitary or <20 mm in diameter). Additionally, hs-AFP-L3% was significantly increased in patients with well-differentiated HCC. In patients with serum AFP <20 ng/ml, the sensitivities of c-AFP-L3% and hs-AFP-L3% were 12.5 and 44.6%, respectively, at a cut-off value of 5%. In 59 BLD patients with serum AFP <20 ng/ml, the HCC-positive rate in patients with hs-AFP-L3% ≥5% was significantly higher compared to those with hs-AFP-L3% <5% during the follow-up period (median, 35 months; range, 5-48 months). Importantly, none of the BLD patients with both serum AFP <20 ng/ml and hs-AFP-L3% <5% developed HCC. These results indicated that hs-AFP-L3% is useful for early detection of HCC in BLD patients, even for those with serum AFP <20 ng/ml. Furthermore, since hs-AFP-L3% increases before HCC is detectable by various advanced imaging modalities, this assay may help identify BLD patients with a higher risk of HCC. IntroductionHepatocellular carcinoma (HCC) is the sixth most common cancer in the world, and the third most common cause of cancer-related death (1). Although it is more common in Asia and Africa, its incidence in the United States has increased over the past two decades, largely due to the spread of hepatitis C (HCV) infection, which is an underlying risk factor (2). Early detection of HCC increases the potential for curative treatment and improves prognosis. Several methods developed for the diagnosis of HCC, including evaluation of serum markers, ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI), have been tested clinically. α-fetoprotein (AFP) and des-γ carboxy prothrombin (DCP), serum proteins that are elevated in HCC, are the most widely used markers. Although routine screening offers the best chance for early tumor detection, the reported sensitivities and specificities of elevated serum AFP and DCP levels vary significantly (3-8). Furthermore, serum AFP levels increase in only 30-40% of patients with HCC, especially early in the disease process (5). Additionally, an increase in serum AFP is also seen in patients with non-cancerous conditions, including cirrhosis or exacerbation of chronic hepatitis (9). AFP-L3, the lectin lens culinaris agglutinin-bound fraction, is one of the three glycoforms of AFP, and is the major glycoform elevated in the serum of HCC patients. The reported sensitivities of AFP-L3 as a method of detecting HCC range from 75-97% with specificities of 90-92% (10,11). In cases of HCC, however, h...

Biomarkers for Hepatocellular Carcinoma

“…Another drawback for AFP-L3 is that its shows little diagnostic value in HCC patients with a total serum AFP concentration below 20 ng/mL. In this regard, the hs-AFP-L3 assay was found by Oda and colleagues22 to show clinical value for early HCC diagnosis even at low AFP levels.…”

Biomarkers in Diagnosis and Prediction of Hepatocellular Carcinoma Recurrence (Review)

“…Therefore, tumors producing no AFP cannot be detected by this method [23]. To overcome this disadvantage, a highly sensitive assay (hs-AFP-L3) has been developed in Japan which is applicable at low values of total AFP in the blood [82].…”

Circulating specific biomarkers in diagnosis of hepatocellular carcinoma and its metastasis monitoring

“…Molecular factors are involved in the process of HCC development and metastasis [92, 93]. Several laboratories have implicated constitutive activation of miRNA as one of the early key events involving in liver neoplastic progression [94, 95]. Further studies will permit us to analyze the mechanism of hepatocarcinogenesis and to pay attention to these areas [96].…”