Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein level as a diagnostic marker of hepatitis B virus-related hepatocellular carcinoma

Aim: Serum glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA(+)-M2BP) is a novel marker for staging liver fibrosis and predicting hepatocellular carcinoma (HCC) occurrence. This study aimed at evaluating the performance of WFA(+)-M2BP in the diagnosis of HCC in patients with chronic hepatitis B virus (HBV) infection. Methods: The WFA(+)-M2BP levels were measured in stored samples collected at initial diagnosis of 150 patients with HBV-related HCC and 150 age- and gender-matched patients with non-malignant chronic HBV infection. Results: Patients with HCC had higher levels of WFA(+)-M2BP than those without HCC (3.9 [1.5-20.6] vs. 1.6 [0.4-9.3] cut-off index [COI], P < 0.001). In the HCC group, WFA(+)-M2BP levels correlated with Child-Pugh classification but did not correlate with HBV markers, -fetoprotein (AFP), or Barcelona Clinic Liver Cancer (BCLC) stage. The areas under the curve (AUROC) for differentiating HCC from non-HCC were 0.92 (95% confidence interval [CI], 0.89-0.95; P < 0.001) for WFA(+)-M2BP, 0.90 (95% CI, 0.87-0.94; P < 0.001) for AFP, and 0.97 (95% CI, 0.95-0.98; P < 0.001) for the combination of both markers. At the optimal cut-off (2.4 COI), WFA(+)-M2BP had sensitivity, specificity, and accuracy of 79.3%, 91.3%, and 85.3%, respectively. The WFA(+)-M2BP marker was superior to AFP in differentiating early-stage HCC (BCLC stages 0 and A) from cirrhosis with AUROC of 0.80 (95% CI, 0.68-0.91; P < 0.001) and 0.73 (95% CI, 0.60-0.86; P = 0.002), respectively. By univariate analysis, elevated WFA(+)-M2BP (>= 4.0 COI) was correlated with poor overall survival in patients with HCC. Conclusions: Wisteria floribunda agglutinin-positive M2BP showed a better diagnostic performance than AFP in detecting early-stage HCC. Thus, WFA(+)-M2BP level could represent a promising marker for early diagnosis of HCC in patients with chronic HBV infection.