{"doi":"10.2147/jhc.s287800","title":"Imaging, Pathology, and Immune Correlates in the Woodchuck Hepatic Tumor Model","abstract":"BACKGROUND: Woodchucks chronically infected with woodchuck hepatitis virus (WHV), which resembles human hepatitis B virus, develop spontaneous hepatic tumors and may be an important biological and immunological model for human HCC. Nonetheless, this model requires further validation to fully realize its translational potential. METHODS: Woodchucks infected at birth with WHV that had developed HCC (n=12) were studied. Computed tomography, ultrasound, and magnetic resonance imaging were performed under anesthesia. LI-RADS scoring and correlative histologic analysis of sectioned tissues were performed. For immune characterization of tumors, CD3 (T cells), CD4 (T helpers), NCAM (Natural killers), FOXP3 (T-regulatory), PDL-1 (inhibitory checkpoint protein), and the human hepatocellular carcinoma (HCC) biomarker alpha-fetoprotein (AFP) immunohistochemical stains were performed. RESULTS: Forty tumors were identified on imaging of which 29 were confirmed to be HCC with 26 categorized as LR-4 or 5. The remainder of the tumors had benign histology including basophilic foci, adenoma, and lipidosis as well as pre-malignant dysplastic foci. LR-4 and LR-5 lesions showed high sensitivity (90%) and specificity (100%) for malignant and pre-malignant tumors. Natural killers count was found to be 2-5 times lower in tumors relative to normal parenchyma while other immune cells were located in the periphery of tumors. Tumors expressed AFP and did not express PD-L1. CONCLUSION: Woodchucks chronically infected with WHV developed diverse hepatic tumor types with diagnostic imaging, pathology, and immune patterns comparable to that in humans. This unique animal model may provide a valuable tool for translation and validation of novel image-guided and immune-therapeutic investigations.","journal":"Journal of Hepatocellular Carcinoma","year":2021,"id":199839,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8456,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":411799,"name":"Andrew S. Mikhail","orcid":"0000-0001-9206-5765","position":1,"is_corresponding":false},{"id":389943,"name":"Matthew F. Starost","orcid":"0000-0002-6234-4875","position":2,"is_corresponding":false},{"id":110327,"name":"Elizabeth C. Jones","orcid":"0000-0003-4914-8180","position":3,"is_corresponding":false},{"id":641691,"name":"Baktiar Karim","orcid":"0000-0001-9604-9762","position":4,"is_corresponding":false},{"id":225662,"name":"David E. Kleiner","orcid":"0000-0003-3442-4453","position":5,"is_corresponding":false},{"id":449879,"name":"Ari Partanen","orcid":"0000-0003-1985-149X","position":6,"is_corresponding":false},{"id":411797,"name":"J. Esparza-Trujillo","orcid":"0000-0002-9660-9130","position":7,"is_corresponding":false},{"id":411800,"name":"Ivane Bakhutashvili","orcid":"0000-0003-3706-1491","position":8,"is_corresponding":false},{"id":389930,"name":"Paul Wakim","orcid":"0000-0002-5951-0983","position":9,"is_corresponding":false},{"id":316710,"name":"Michael Kassin","orcid":"0000-0001-6065-8523","position":10,"is_corresponding":false},{"id":536325,"name":"Andrew L. Lewis","orcid":"0000-0001-5779-5631","position":11,"is_corresponding":false},{"id":328995,"name":"John W. Karanian","orcid":"0000-0002-0574-4231","position":12,"is_corresponding":false},{"id":110338,"name":"Bradford J. Wood","orcid":"0000-0002-4297-0051","position":13,"is_corresponding":false},{"id":292052,"name":"William F. Pritchard","orcid":"0000-0001-5805-5344","position":14,"is_corresponding":false},{"id":411798,"name":"Michal Mauda‐Havakuk","orcid":"0000-0002-8810-3455","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-18T23:50:44.479665Z","pmid":"33728278","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}