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Updated: Sep 26, 2025
Establishment and Genetic Manipulation of Murine Hepatocyte Organoids
Published on: February 12, 2022
Generation, Maintenance and HBV Infection of Human Liver Organoids
Shahla Romal1, Tanvir Hossain1, Tokameh Mahmoudi1,2,3
1Department of Biochemistry, Erasmus University Medical Center, The Netherlands.
Insights
Human liver organoids offer a new in vitro model for studying Hepatitis B virus (HBV) infection and its link to liver cancer. This platform aids in understanding HBV pathogenesis and developing personalized treatments.
Area of Science:
- Hepatology and Virology
- Regenerative Medicine
- Cancer Biology
Background:
- Hepatitis B virus (HBV) infects 400 million globally, causing chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC).
- Current antiviral therapies and vaccines are insufficient for complete eradication, highlighting the need for better research models.
- A significant obstacle in developing curative strategies is the lack of suitable in vitro models to study HBV replication, latency, and carcinogenesis.
Purpose of the Study:
- To establish and validate human liver organoids as a novel in vitro model for Hepatitis B virus (HBV) infection.
- To investigate the potential of liver organoids in studying HBV pathogenesis, drug screening, and modeling HBV-related liver diseases, including HCC.
- To explore the utility of organoids derived from cirrhotic liver biopsies for personalized medicine approaches.
Main Methods:
- Human liver organoids were generated from healthy and cirrhotic liver biopsies.
- Organoids were expanded in vitro using specific growth factor-containing media.
- Differentiation into functional hepatocytes was induced by changing the culture medium, rendering them susceptible to recombinant HBV infection.
Main Results:
- The developed human liver organoid system successfully supported HBV infection.
- Organoids demonstrated susceptibility to HBV, enabling the study of viral replication and pathogenesis in vitro.
- Organoids derived from cirrhotic biopsies showed potential for modeling disease progression and testing personalized therapies.
Conclusions:
- Human liver organoids provide a robust and relevant in vitro platform for studying Hepatitis B virus (HBV) infection and pathogenesis.
- This model system facilitates HBV drug screening and the investigation of HBV-associated liver diseases, including hepatocellular carcinoma (HCC).
- Liver organoids derived from patient biopsies offer a promising avenue for personalized medicine and the study of complex liver conditions.
Abstract:
Hepatitis B virus (HBV) infection represents a major public health problem infecting approximately 400 million people worldwide. Despite the availability of a preventive vaccine and anti-viral therapies, chronic HBV infection remains a major health issue because it increases the risk of developing liver cirrhosis and hepatocellular carcinoma (HCC). The lack of a relevant in vitro model for the study of the molecular mechanisms that drive HBV replication and latency, as well as HBV-related carcinogenesis, has been one of the major obstacles to the development of curative strategies. Here, we propose the use of human liver organoids as a platform for modeling HBV infection and related tumorigenesis. Human liver organoids can be seeded from both healthy and cirrhotic liver biopsies. They can be expanded in vitro when culturing in a medium containing a specific set of growth factors. When the culture medium is changed into a new medium containing growth factors that promote differentiation, organoids differentiate into functional hepatocytes, which makes them susceptible to infection with recombinant HBV. The novel in vitro primary model system described in this protocol can be utilized as a platform to study HBV pathogenesis and drug screening. Organoids generated from cirrhotic liver biopsies can be a potential tool for personalized medicine, and for modeling HCC and other liver diseases. Graphic abstract.
