Liver Abnormalities after Elimination of HCV Infection: Persistent Epigenetic and Immunological Perturbations Post-Cure
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Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA
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Department of Global Health, University of Washington, Seattle, WA 98195, USA
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Department of Microbiology, University of Washington, Seattle, WA 98195, USA
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Department of Immunology, University of Washington, Seattle, WA 98195, USA
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Institut de Recherche sur les Maladies Virales et Hépatiques, Université de Strasbourg, Inserm U1110, 67000 Strasbourg, France
6
Pole Hépato-digestif, IHU, Hopitaux Universitaires de Strasbourg, 67000 Strasbourg, France
*
Authors to whom correspondence should be addressed.
Pathogens 2021, 10(1), 44; https://doi.org/10.3390/pathogens10010044
Received: 13 December 2020
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Revised: 2 January 2021
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Accepted: 5 January 2021
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Published: 7 January 2021
(This article belongs to the Special Issue Hepatitis C Virus: Remaining Challenges)
Chronic hepatitis C (CHC) is a major cause of hepatocellular carcinoma (HCC) worldwide. While directly acting antiviral (DAA) drugs are now able to cure virtually all hepatitis C virus (HCV) infections, even in subjects with advanced liver disease, what happens to the liver and progression of the disease after DAA-induced cure of viremia is only beginning to emerge. Several large-scale clinical studies in different patient populations have shown that patients with advanced liver disease maintain a risk for developing HCC even when the original instigator, the virus, is eliminated by DAAs. Here we review emerging studies derived from multiple, complementary experimental systems involving patient liver tissues, human liver cell cultures, human liver slice cultures, and animal models, showing that HCV infection induces epigenetic, signaling, and gene expression changes in the liver associated with altered hepatic innate immunity and liver cancer risk. Of critical importance is the fact that these virus-induced abnormalities persist after DAA cure of HCV. These nascent findings portend the discovery of pathways involved in post-HCV immunopathogenesis, which may be clinically actionable targets for more comprehensive care of DAA-cured individuals.
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Keywords:
hepatitis C virus; DAA; liver cancer; HCC; epigenetic; innate immunity
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MDPI and ACS Style
Polyak, S.J.; Crispe, I.N.; Baumert, T.F. Liver Abnormalities after Elimination of HCV Infection: Persistent Epigenetic and Immunological Perturbations Post-Cure. Pathogens 2021, 10, 44. https://doi.org/10.3390/pathogens10010044
AMA Style
Polyak SJ, Crispe IN, Baumert TF. Liver Abnormalities after Elimination of HCV Infection: Persistent Epigenetic and Immunological Perturbations Post-Cure. Pathogens. 2021; 10(1):44. https://doi.org/10.3390/pathogens10010044
Chicago/Turabian StylePolyak, Stephen J., I. N. Crispe, and Thomas F. Baumert. 2021. "Liver Abnormalities after Elimination of HCV Infection: Persistent Epigenetic and Immunological Perturbations Post-Cure" Pathogens 10, no. 1: 44. https://doi.org/10.3390/pathogens10010044
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