Liver Abnormalities after Elimination of HCV Infection: Persistent Epigenetic and Immunological Perturbations Post-Cure

Pathogens

StephenJ. Polyak¹  I.Nicholas Crispe¹  ThomasF. Baumert² 

[1] Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA;Institut de Recherche sur les Maladies Virales et Hépatiques, Université de Strasbourg, Inserm U1110, 67000 Strasbourg, France;

关键词: hepatitis C virus;    DAA;    liver cancer;    HCC;    epigenetic;    innate immunity;   

DOI  :  10.3390/pathogens10010044

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown