Liver Stiffness Characterization of OGTMouse Model of Progressive Liver Fibrosis.

Abstract

OBJECTIVES: O-GlcNAcylation plays a key regulatory role in hepatic physiology, and its disruption leads to fibrosis in liver-specific OGT knockout mice (OGT), making this model valuable for studying advanced metabolic dysfunction-associated steatohepatitis (MASH). Our objective is to demonstrate that shear wave elastography (SWE) is a suitable non-invasive tool to characterize and follow this mouse model of liver injury. METHODS: We weekly monitored non-invasively liver fibrosis progression in OGTmice from 5 to 8 weeks of age, using SWE on both a high-frequency preclinical ultrasound system (VevoF2), and a clinical reference system (Aixplorer) and assuming the liver as homogeneous, isotropic and purely elastic. Stiffness measurements were then confronted with ex vivo liver histological scoring and major gene transcripts associated with the development of the pathology. RESULTS: Weekly liver stiffness measurements demonstrated a progressive increase, correlating strongly with histological fibrosis scores (R > 0.78) and fibrosis-related gene expression (Col3a1, Col6a1). The high-resolution imaging capability of the VevoF2 allowed precise anatomical exploration while delivering SWE measurements consistent with the clinical device (Pearson r = 0.92). CONCLUSION: Our study confirms that following liver stiffness fibrosis by SWE in a mouse model of liver injury is a valuable tool that correlates with ex vivo findings. This approach facilitates a better understanding of disease progression and therapeutic evaluation in preclinical models of MASH.