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Increased hepatic interstitial pressure can be observed in patients with advanced liver disease and is associated with worsened clinical outcomes. Elevated hepatic stiffness has been reported clinically with increases in hepatic venous pressure gradient (HVPG). An experiment was designed to determine whether stiffness increase exhibited with hepatic pressurization results from a strain-dependent hyperelastic behavior. Six excised canine livers were subjected to variations in interstitial pressure through cannulation of the portal vein and closure of the hepatic artery and hepatic vein under constrained conditions (in which the liver was not free to expand) and unconstrained conditions. Radiation force derived shear wave speed estimates were obtained and correlated with pressure. Estimates of hepatic shear stiffness increased with changes in interstitial pressure over a physiologically relevant range of pressures (0-35mmHg) from 1.5 to 3.5 m/s. These increases were observed only under conditions in which the liver was free to expand while pressurized.