Treatment options for liver diseases, including hepatitis B, remain limited, and many patients ultimately require a liver transplant. New ways to study the liver are critical for developing therapeutic interventions and filling this treatment gap. Researchers at UHN have created the first comprehensive atlas of liver and immune cells in a widely used preclinical model of chronic Hepatitis B Virus (HBV) infection—a development that could accelerate research into the disease and its progression to liver cancer.
The liver is a vital organ that regulates chemicals in the blood. HBV is a virus that can cause a lifelong (chronic) infection that leads to serious illnesses such as liver scarring and liver cancer (hepatocellular carcinoma, HCC). In end-stage liver disease, the liver can no longer regenerate after injury, making transplantation the primary treatment option.
Studying HBV infection, including disease progression and treatment, remains challenging because there are few experimental models and limited human tissue availability. To address this, researchers sought to characterize a commonly used preclinical model of HBV at a cellular level.
The team generated an atlas of single-cell gene expression data that also includes information on which genes are expressed in which parts of the liver. This atlas captures how tens of thousands of liver and immune cells behave in both healthy conditions and during chronic viral infection in the HBV model.
Using this atlas, the researchers found that the cell population in this preclinical model is comparable to human livers and the immune cells trigger the same kinds of inflammatory responses. The liver atlas also showed that HBV infections in this model lead to gene expression and cellular changes similar to those in the human liver. HBV infections in both the model and in humans activate certain immune cells, called dendritic cells, in the same area of the liver, and T cells become “worn out” over time.
This study highlights that HBV infection affects this well-known preclinical model in similar ways to humans, confirming the model’s importance in liver disease research. This atlas, therefore, offers a powerful new tool for understanding HBV and developing better treatments.
Zoe Clarke, Jawairia Atif, and Xinle Wang are co-first authors of the study. Zoe Clarke is a PhD Candidate at the University of Toronto (U of T), Dr. Jawairia Atif is a PhD graduate at UHN, and Xinle Wang is a former research student at UHN and a current medical student at U of T.
Dr. Ian McGilvary, Senior Scientist at UHN and Dr. Gary Bader, Affiliate Scientist at Princess Margaret Cancer Centre are co-senior authors of the study. Dr. McGilvary is also a Professor in the Department of Surgery at U of T. Dr. Bader is also a Professor in the Department of Molecular Genetics at U of T.
Dr. Sonya MacParland, a Senior Scientist at UHN, the Research Director of the Ajmera Transplant Centre, and a Professor in the Department of Laboratory Medicine and Pathobiology at U of T, is the co-senior and corresponding author of the study.
This work was supported by the University of Toronto McLaughlin Centre, Canadian Liver Foundation, the Natural Sciences and Engineering Research Council, the Canadian Institutes for Health Research, and UHN Foundation.
Sonya MacParland is a Tier 2 Canada Research Chair in Liver Immunobiology.
Clarke ZA, Atif J, Wang X, Liu LY, Wood L, Camat D, Liu Y, Shiwram A, Hyduk SJ, Chung S, Ma XZ, Manuel J, Lok S, Lau TNH, Thoeni C, Michalak TI, McGilvray ID, Bader GD, MacParland SA. A single-cell atlas of the woodchuck liver reveals cellular programs conserved in human HBV infection. J Hepatol. 2026 Jan 22:S0168-8278(26)00019-X. doi: 10.1016/j.jhep.2025.12.030. Epub ahead of print.
