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Updated: Jul 21, 2025
"Liver-on-a-Chip" Cultures of Primary Hepatocytes and Kupffer Cells for Hepatitis B Virus Infection
Published on: February 19, 2019
Cell Culture Systems for Studying Hepatitis B and Hepatitis D Virus Infections
Grace Sanghee Lee1, Michael A Purdy1, Youkyung Choi1
1Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention, US Centers for Disease Control and Prevention (CDC), Atlanta, GA 30333, USA.
Insights
Developing effective cell culture models is crucial for advancing treatments for hepatitis B virus (HBV) and hepatitis D virus (HDV) infections. New models like HepG2-NTCP and SACC-PHHs offer improved tools for studying these liver diseases and finding new antiviral therapies.
Area of Science:
- Hepatology and Virology
- Infectious Diseases
- Drug Discovery
Background:
- Hepatitis B virus (HBV) and hepatitis D virus (HDV) cause significant global liver disease, including cancer.
- Chronic HBV affects millions, with a notable percentage co-infected by HDV.
- Current treatments for HBV are suppressive, not curative, and no effective HDV treatment exists.
Purpose of the Study:
- To highlight the critical need for improved in vitro cell culture systems for studying HBV and HDV.
- To explore recent advancements in cell culture models for understanding viral pathogenesis and developing therapeutics.
- To identify how enhanced cell culture systems can accelerate the discovery of novel antiviral strategies.
Main Methods:
- Review of existing and novel in vitro cell culture systems for HBV and HDV.
- Discussion of cell lines such as HepG2-NTCP and co-cultured primary human hepatocytes (SACC-PHHs).
- Analysis of how these systems facilitate the study of viral life cycles and drug target identification.
Main Results:
- The development of HepG2-NTCP and SACC-PHHs represents significant progress in HBV/HDV research.
- These advanced models offer better insights into HBV and HDV infection mechanisms.
- Improved cell culture systems are essential for overcoming limitations in current antiviral drug development.
Conclusions:
- Robust cell culture models are indispensable for advancing the understanding and treatment of HBV and HDV infections.
- Recent innovations in cell culture technology provide powerful new tools for therapeutic development.
- Further research utilizing these advanced models is critical for discovering curative therapies for HBV and HDV.
Abstract:
The hepatitis B virus (HBV) and hepatitis D virus (HDV) infections cause liver disease, including hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). HBV infection remains a major global health problem. In 2019, 296 million people were living with chronic hepatitis B and about 5% of them were co-infected with HDV. In vitro cell culture systems are instrumental in the development of therapeutic targets. Cell culture systems contribute to identifying molecular mechanisms for HBV and HDV propagation, finding drug targets for antiviral therapies, and testing antiviral agents. Current HBV therapeutics, such as nucleoside analogs, effectively suppress viral replication but are not curative. Additionally, no effective treatment for HDV infection is currently available. Therefore, there is an urgent need to develop therapies to treat both viral infections. A robust in vitro cell culture system supporting HBV and HDV infections (HBV/HDV) is a critical prerequisite to studying HBV/HDV pathogenesis, the complete life cycle of HBV/HDV infections, and consequently identifying new therapeutics. However, the lack of an efficient cell culture system hampers the development of novel antiviral strategies for HBV/HDV infections. In vitro cell culture models have evolved with significant improvements over several decades. Recently, the development of the HepG2-NTCP sec+ cell line, expressing the sodium taurocholate co-transporting polypeptide receptor (NTCP) and self-assembling co-cultured primary human hepatocytes (SACC-PHHs) has opened new perspectives for a better understanding of HBV and HDV lifecycles and the development of specific antiviral drug targets against HBV/HDV infections. We address various cell culture systems along with different cell lines and how these cell culture systems can be used to provide better tools for HBV and HDV studies.
