Abstract
BackgroundTo investigate the von Willebrand factor to ADAMTS13 ratio as a potential biomarker for early detection of hepatocellular carcinoma (HCC) in cirrhosis.MethodsSerum levels of alpha-fetoprotein, des-γ-carboxy prothrombin, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (alpha-fetoprotein-L3%), vascular endothelial growth factor, and vascular endothelial growth factor receptor-2, as well as the plasma levels of von Willebrand factor antigen (von Willebrand factor: Ag) and ADAMTS13 activity (ADAMTS13:AC), were evaluated in 41 cirrhotic patients with HCC undergoing radiofrequency ablation and in 20 cirrhotic patients without HCC. The diagnostic accuracy of each biomarker was evaluated using the receiver operating characteristic curve analysis.ResultsThe von Willebrand factor: Ag and von Willebrand factor: Ag/ADAMTS13:AC ratios were significantly higher in cirrhotic patients with HCC than in those without HCC (p < 0.05 and p < 0.01, respectively), whereas ADAMTS13:AC was significantly lower in those with HCC than those without HCC (p < 0.05). However, no relationship was observed between the von Willebrand factor: Ag/ADAMTS13:AC ratio and serum tumor markers such as alpha-fetoprotein, des-γ-carboxy prothrombin, and alpha-fetoprotein-L3%. Multivariate regression analysis identified von Willebrand factor: Ag/ADAMTS13:AC ratio and alpha-fetoprotein-L3% as significant factors of HCC development. Receiver operating characteristic analysis showed that the von Willebrand factor: Ag/ADAMTS13:AC ratio and alpha-fetoprotein-L3% had a better performance than alpha-fetoprotein, des-γ-carboxy prothrombin, alpha-fetoprotein-L3%, vascular endothelial growth factor, and vascular endothelial growth factor receptor-2, von Willebrand factor: Ag, and ADAMTS13:AC. The von Willebrand factor: Ag/ADAMTS13:AC ratio was exclusively correlated with tumor volume and stage as well as serum vascular endothelial growth factor levels.ConclusionsThe von Willebrand factor: Ag/ADAMTS13:AC ratio can potentially serve as a novel biomarker for early diagnosis of HCC in cirrhotic patients.
Highlights
To investigate the von Willebrand factor to ADAMTS13 ratio as a potential biomarker for early detection of hepatocellular carcinoma (HCC) in cirrhosis
The alpha fetoprotein (AFP)-L3%, GALAD score, vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2) levels, as well as the von Willebrand factor (VWF):Ag and VWF:Ag/ADAMTS13:AC ratio, were significantly higher in cirrhotic patients with HCC than in those without HCC (p < 0.01, p < 0.01, p < 0.05, p < 0.01, p < 0.05, and p < 0.01, respectively) (Fig. 1 c, d, e, g, and h)
Correlation of the VWF:ag/ADAMTS13:AC ratio with conventional tumor markers and platelet count We examined the relationship between the VWF:Ag/ ADAMTS13:AC ratio and serum tumor markers, such as AFP, des-γ-carboxy prothrombin (DCP), and AFP-L3%
Summary
To investigate the von Willebrand factor to ADAMTS13 ratio as a potential biomarker for early detection of hepatocellular carcinoma (HCC) in cirrhosis. The professional society guidelines from the European Association for the Study of the Liver [5] and American Association for the Study of Liver Diseases [6] encourage surveillance using ultrasonography at every 6 months in patients with cirrhosis They do not agree with the addition of alpha fetoprotein (AFP) as an adjunct surveillance test. The Japan Society of Hepatology Consensus-Based Clinical Practice Guidelines for the Management of HCC recommends the use of three tumor markers AFP, des-γ-carboxy prothrombin (DCP), and alpha-fetoprotein-L3% (AFP-L3) in combination with ultrasonography [7]. This approach has contributed to increase the detection of small HCCs in Japan in comparison to that in Europe and America. Universally available biological markers for the early diagnosis of HCC are urgently needed to improve the survival rate among patients with cirrhosis
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