The Woodchuck Hepatitis Virus Model of Hepatocellular Carcinoma for Interventional Radiology Research

Preclinical models that accurately recapitulate the pathogenesis, microenvironment, and therapeutic response of human hepatocellular carcinoma (HCC) are essential for advancing locoregional therapies. The woodchuck (Marmota monax) chronically infected with woodchuck hepatitis virus (WHV) offers a unique and highly translational large-animal model for HCC research. This manuscript reviews the utility of the WHV-woodchuck model, emphasizing its strengths in mimicking human HCC pathophysiology and its applicability to interventional radiology-based research. Unlike xenograft or chemically induced rodent models, WHV-infected woodchucks develop spontaneous HCC on a background of chronic viral hepatitis, is somewhat similar to the human disease in both tumorigenesis and tumor immune microenvironment. This makes the model particularly valuable for studying tumor-host interactions and assessing therapeutic responses in an immunocompetent setting. Importantly, the woodchuck size of 2-5kg permits the application of standard imaging and interventional techniques, including image-guided tumor ablation and transcatheter arterial embolization. The ability to perform serial imaging, targeted biopsies and localized therapies in this model provides a powerful platform for translational research in interventional oncology. While the model has logistical challenges, including seasonal breeding and specialized husbandry and care requirements, its unique advantages make it one of the most relevant preclinical systems for studying locoregional therapies in HCC.