Effects of Vascularity and Differentiation of Hepatocellular Carcinoma on Tumor and Liver Stiffness: In Vivo and in Vitro Studies

Tissue stiffness has been found to be a useful predictor of malignancy in various cancers. However, data on the stiffness of hepatocellular carcinomas (HCCs) and their background livers are contradictory. The aim of this study was to investigate the effects of vascularity and histologic differentiation on HCC stiffness. Elastography point quantification (ElastPQ), a new shear wave-based elastography method, was used to measure liver stiffness in vivo in 99 patients with pathology-proven HCC. Lesion vascularity was assessed using contrast-enhanced ultrasound, computed tomography and/or magnetic resonance imaging. The association of HCC vascularity and differentiation with liver stiffness was determined. In addition, in vitro stiffness of 20 of the 99 surgical HCC specimens was mechanically measured and compared with in vivo measurements. We found that in vivo stiffness was significantly higher than in vitro stiffness in both HCCs and their background livers (p < 0.0001). Moreover, significantly higher stiffness was observed in hyper-vascular and poorly differentiated lesions than in hypo-vascular (p = 0.0352) and moderately to well-differentiated lesions (p = 0.0139). These in vivo and in vitro studies reveal that shear wave-based ultrasound elasticity quantification can effectively measure in vivo liver stiffness.