Multimodal assessment of liver stiffness and portal hemodynamics in a cirrhotic mouse model.

Elevated pressure within the portal venous system defines portal hypertension. While extensive research has focused on its biochemical basis, the biomechanical characteristics of liver tissue in this condition remain largely unexplored. We established a carbon tetrachloride (CCl4) -induced murine model to investigate dynamic changes in liver biomechanics and their associations with hemodynamics, fibrosis, and hepatocellular injury. Portal hypertension was induced in six-week-old male BALB/c mice by intraperitoneal CCl4. Ultrasound measured surrogate hemodynamic indices such as resistance index, flow velocity, and spleen size. Uniaxial tensile testing obtained liver Young's modulus. Second harmonic generation and histology evaluated collagen microstructure. Serum biomarkers by enzyme-linked immunosorbent assay. Collagen deposition was significantly and positively correlated with liver stiffness (r = 0.7232; p < 0.0001). Liver stiffness also correlated with the portal venous pulsatility index (r = 0.6477, p = 0.0005). Serum biomarkers, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT), were positively correlated with liver stiffness (AST: r = 0.6596, p = 0.0016; ALT: r = 0.8451, p < 0.0001). Expression levels of α-smooth muscle actin (α-SMA) and Matrix Metallopeptidase-9 (MMP-9) were significantly associated with increased stiffness (α-SMA: r = 0.6837; p = 0.0002; MMP-9: r = 0.7365; p < 0.0001). In CCl4-induced cirrhosis, liver stiffness correlates temporally with portal resistance, collagen deposition, and HSC activation, suggesting a potential mechanobiological contribution to portal hypertension pending causal validation, with interrelated hepatocellular injury, inflammation, and ECM deposition.