In-vitro and in-vivo models for hepatitis B cure research

Antiviral therapy for chronic hepatitis B infection is rarely curative, thus research in HBV cure strategies is a priority. Drug development and testing has been hampered by the lack of robust cell culture systems and small animal models. This review summarizes existing models for HBV cure research and focuses on recent developments since 2017 until today.

The field has progressed in the development of cell culture and animal models to study HBV. Although early cell culture systems relied on transfection of HBV genomes in hepatoma cell lines, novel models expressing the entry receptor for HBV are susceptible to infection. Improved culture conditions for primary human hepatocytes, the primary target of HBV, have enabled the screening and validation of novel antivirals. Mouse models grafted with partially humanized livers are suitable for testing viral entry inhibitors or direct acting antivirals, and can be reconstituted with human immune cells to analyze immunotherapies. Other immunocompetent models include mice transduced with HBV genomes or woodchucks infected with their native hepatitis virus.

Model systems for HBV research have helped lay the groundwork for the development and optimization of antiviral and immune-based therapeutic approaches that are now moving to clinical trials.