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  • Review Article
  • Published:

Experimental models of hepatitis B and C — new insights and progress

Nature Reviews Gastroenterology & Hepatology volume 13, pages 362–374 (2016)Cite this article

Subjects

Key Points

  • Early work on viral hepatitis relied on biochemical methods and microscopy, but the field greatly benefited from the use of primates and other animal models of both acute and chronic infection

  • Use of tumour-derived cells lines has increased our understanding of viral hepatitis; small molecule screens were performed in cell lines expressing viral genomes to identify agents that could suppress viral replication

  • Primary human hepatocytes are considered the most biologically relevant in vitro model for viral hepatitis infections; advances in propagation of stem cells in culture have led to exciting new stem-cell-derived hepatocyte models

  • Hepatocytes and other epithelial cells exist and function in a highly structured system and in vitro models are moving to those that incorporate multiple nonparenchymal cells and 3D lattices to preserve full hepatocyte function

  • Mouse models were initially limited by species-specific barriers, but transgenic animals can used to study immune responses and species-specific barriers can be overcome through the generation of humanized mice

  • Further progress in recapitulating human immune responses in mouse models might facilitate the development of an HCV vaccine, with in vitro models of HBV cccDNA persistence aiding discovery of anti-HBV small molecules

Abstract

Viral hepatitis is a major cause of morbidity and mortality, affecting hundreds of millions of people worldwide. Hepatitis-causing viruses initiate disease by establishing both acute and chronic infections, and several of these viruses are specifically associated with the development of hepatocellular carcinoma. Consequently, intense research efforts have been focusing on increasing our understanding of hepatitis virus biology and on improving antiviral therapy and vaccination strategies. Although valuable information on viral hepatitis emerged from careful epidemiological studies on sporadic outbreaks in humans, experimental models using cell culture, rodent and non-human primates were essential in advancing the field. Through the use of these experimental models, improvement in both the treatment and prevention of viral hepatitis has progressed rapidly; however, agents of viral hepatitis are still among the most common pathogens infecting humans. In this Review, we describe the important part that these experimental models have played in the study of viral hepatitis and led to monumental advances in our understanding and treatment of these pathogens. Ongoing developments in experimental models are also described.

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Figure 1: HBV biology.
Figure 2: HCV biology.
Figure 3: The evolving models to study the HCV life cycle and pathogenesis.
Figure 4: The evolving models to study the HBV life cycle and pathogenesis.

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Acknowledgements

E.T. acknowledges funding support from the Miami Center for AIDS Research, Leonard M. Miller School of Medicine, USA (P30AI073961) and a the Miami CTSI KL2 program.

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  1. Schiff Center for Liver Diseases and Sylvester Cancer Center, Room PAP514, Papanicolaou Building, 1550 NW 10th Avenue, Miami, 33136, Florida, USA

    Emmanuel Thomas

  2. Liver Diseases Branch, NIH, Building 10-9B16, Bethesda, 20892–1800, Maryland, USA

    T. Jake Liang

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Thomas, E., Liang, T. Experimental models of hepatitis B and C — new insights and progress. Nat Rev Gastroenterol Hepatol 13, 362–374 (2016). https://doi.org/10.1038/nrgastro.2016.37

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