Cargando…

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

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 di...

Descripción completa

Detalles Bibliográficos
Autores principales: Polyak, Stephen J., Crispe, I. Nicholas, Baumert, Thomas F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825776/
https://www.ncbi.nlm.nih.gov/pubmed/33430338
http://dx.doi.org/10.3390/pathogens10010044
_version_ 1783640386407759872
author Polyak, Stephen J.
Crispe, I. Nicholas
Baumert, Thomas F.
author_facet Polyak, Stephen J.
Crispe, I. Nicholas
Baumert, Thomas F.
author_sort Polyak, Stephen J.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7825776
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-78257762021-01-24 Liver Abnormalities after Elimination of HCV Infection: Persistent Epigenetic and Immunological Perturbations Post-Cure Polyak, Stephen J. Crispe, I. Nicholas Baumert, Thomas F. Pathogens Review 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. MDPI 2021-01-07 /pmc/articles/PMC7825776/ /pubmed/33430338 http://dx.doi.org/10.3390/pathogens10010044 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Polyak, Stephen J.
Crispe, I. Nicholas
Baumert, Thomas F.
Liver Abnormalities after Elimination of HCV Infection: Persistent Epigenetic and Immunological Perturbations Post-Cure
title Liver Abnormalities after Elimination of HCV Infection: Persistent Epigenetic and Immunological Perturbations Post-Cure
title_full Liver Abnormalities after Elimination of HCV Infection: Persistent Epigenetic and Immunological Perturbations Post-Cure
title_fullStr Liver Abnormalities after Elimination of HCV Infection: Persistent Epigenetic and Immunological Perturbations Post-Cure
title_full_unstemmed Liver Abnormalities after Elimination of HCV Infection: Persistent Epigenetic and Immunological Perturbations Post-Cure
title_short Liver Abnormalities after Elimination of HCV Infection: Persistent Epigenetic and Immunological Perturbations Post-Cure
title_sort liver abnormalities after elimination of hcv infection: persistent epigenetic and immunological perturbations post-cure
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825776/
https://www.ncbi.nlm.nih.gov/pubmed/33430338
http://dx.doi.org/10.3390/pathogens10010044
work_keys_str_mv AT polyakstephenj liverabnormalitiesaftereliminationofhcvinfectionpersistentepigeneticandimmunologicalperturbationspostcure
AT crispeinicholas liverabnormalitiesaftereliminationofhcvinfectionpersistentepigeneticandimmunologicalperturbationspostcure
AT baumertthomasf liverabnormalitiesaftereliminationofhcvinfectionpersistentepigeneticandimmunologicalperturbationspostcure