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)