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Aims  Recent advances of direct‐acting antiviral drugs for hepatitis C virus (HCV) have dramatically improved the sustained virologic response (SVR) rate, but hepatocellular carcinoma (HCC) development rarely occurs even in patients who achieve an SVR. Wisteria floribunda agglutinin‐positive mac‐2‐binding protein (WFA + ‐M2BP) was recently developed as a noninvasive biomarker of liver fibrosis. However, the association between the WFA + ‐M2BP level and HCC development after the achievement of an SVR is unclear.    Methods and Results  We examined the association between WFA + ‐M2BP and HCC development in 522 HCV patients who achieved an SVR (Interferon [IFN]‐based therapy,  n  = 228; IFN‐free therapy,  n  = 294). Multivariate analysis revealed that a high WFA + ‐M2BP level at SVR week 24 after treatment (SVR24) (hazard ratio [HR] = 1.215,  P  = 0.020), low platelet counts (HR = 0.876,  P  = 0.037), and old age (HR = 1.073,  P  = 0.012) were independent risk factors for HCC development regardless of the treatment regimen. Receiver operator characteristics curve analysis revealed that a WFA + ‐M2BP level at SVR24 of ≥1.62 cut‐off index (COI) was the cut‐off value for the prediction of HCC development (adjusted HR = 12.565, 95% CI 3.501–45.092,  P  < 0.001). The 3‐ and 5‐year cumulative incidences of HCC were 1% and 1.6% in patients with low WFA + ‐M2BP at SVR24 (<1.62 COI), and 4.7% and 12.5% in patients with high WFA + ‐M2BP (≥1.62 COI) were, respectively ( P  < 0.001).    Conclusions  The assessment of liver fibrosis using the WFA + ‐M2BP level at SVR24 is a useful predictor of HCC development after HCV eradication even in the IFN‐free therapy era.

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Post‐treatment serum Wisteria floribunda agglutinin‐positive mac‐2‐binding protein level is a useful predictor of hepatocellular carcinoma development after hepatitis C virus eradication