Elevated serum levels of Wisteria floribunda agglutinin‐positive human Mac‐2 binding protein predict the development of hepatocellular carcinoma in hepatitis C patients

Abstract

The Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA+-M2BP) was recently shown to be a liver fibrosis glycobiomarker with a unique fibrosis-related glycoalteration. We evaluated the ability of WFA+-M2BP to predict the development of hepatocellular carcinoma (HCC) in patients who were infected with the hepatitis C virus (HCV). A total of 707 patients who had been admitted to our hospital with chronic HCV infection without other potential risk factors were evaluated to determine the ability of WFA+-M2BP to predict the development of HCC; factors evaluated included age, sex, viral load, genotypes, fibrosis stage, aspartate and alanine aminotransferase levels, bilirubin, albumin, platelet count, alpha-fetoprotein (AFP), WFA+-M2BP, and the response to interferon (IFN) therapy. Serum WFA+-M2BP levels were significantly increased according to the progression of liver fibrosis stage (P < 0.001). In each distinctive stage of fibrosis (F0-F1, F2, F3, and F4), the risk of development of HCC was increased according to the elevation of WFA+-M2BP. Multivariate analysis identified age >57 years, F4, AFP >20 ng/mL, WFA+-M2BP ≥4, and WFA+-M2BP 1-4 as well as the response to IFN (no therapy vs. sustained virological response) as independent risk factors for the development of HCC. The time-dependent areas under the receiver operating characteristic curve demonstrated that the WFA+-M2BP assay predicted the development of HCC with higher diagnostic accuracy than AFP. Conclusion: WFA+-M2BP can be applied as a useful surrogate marker for the risk of HCC development, in addition to liver biopsy. (Hepatology 2014;60:1563–1570)

Clinical Evaluation of Hepatocarcinogenesis and Outcome Using a Novel Glycobiomarker <i>Wisteria floribunda</i> Agglutinin-Positive Mac-2 Binding Protein (WFA⁺-M2BP) in Chronic Hepatitis C with Advanced Fibrosis

“…1B). In a previous report, serum WFA + -M2BP was found useful as a noninvasive predictor of HCC development and was considered a specific marker for liver fibrosis (13). Our results were in accordance with previous findings.…”

“…Our study found a significant increase in the serum WFA + -M2BP level with the progression of liver fibrosis from stage F3 to F4 in CHC patients (Table 1). Similarly, previous studies have found that the serum WFA + -M2BP level is associated with the degree of liver fibrosis obtained by liver biopsy (13,(25)(26)(27)). …”

“…FibroScan (21,22) and transient elastography are established noninvasive methods of assessment. Although FibroScan is a rapid and technically easy method to perform, its diagnostic accuracy depends on the skill of the operator (13). Likewise, stiffness measurements, which include transient elastography, can be difficult to obtain in obese patients and impossible in patients with ascites (21,23).…”

“…Serum WFA + -M2BP was quantified using a lectin-antibody sandwich immunoassay on a fully automatic HISCL2000i immunoanalyzer (Sysmex Co., Kobe, Japan) (8). In this study, according to a previous report (13), serum WFA + -M2BP levels were classified into 3 groups: high (≥ 4 cutoff index [COI]), intermediate (1-4 COI), or low (< 1 COI) levels. Study design: The associations between serum WFA + -M2BP level and the progression of liver fibrosis and hepatocarcinogenesis were evaluated in the study patients.…”

Risk of hepatocellular carcinoma for patients treated with direct-acting antivirals: steps after hepatitis C virus eradication to achieve elimination

“…Conventional or novel biomarkers may provide insights into risk stratification for successfully treated patients. A recent prospective study in Japan revealed that a unique fibrosis-related glycomarker, Wisteria floribunda agglutinin positive Mac-2 binding protein (WFA + M2BP), may predict the development of HCC with a diagnostic accuracy higher than alpha-fetoprotein (11). Elevated serum WFA + M2BP levels in patients had a high correlation with the severity of fibrosis.…”