Viral Hepatitis and Hepatocellular Carcinoma: State of the Art

Viral hepatitis is one of the main causes leading to hepatocellular carcinoma (HCC). The continued rise in incidence of HCC suggests additional factors following infection may be involved. This review examines recent studies investigating the molecular mechanisms of chronic hepatitis and its associa...

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Autores principales:	Toofan Datfar, Michael Doulberis, Apostolis Papaefthymiou, Ian N. Hines, Giulia Manzini
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	viral hepatitis hepatocellular carcinoma HCC cancer risk factor carcinogenesis Medicine R
Acceso en línea:	https://doaj.org/article/f8e9ea0d18cb43e6b94af8b885768254
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spelling	oai:doaj.org-article:f8e9ea0d18cb43e6b94af8b8857682542021-11-25T18:37:39ZViral Hepatitis and Hepatocellular Carcinoma: State of the Art10.3390/pathogens101113662076-0817https://doaj.org/article/f8e9ea0d18cb43e6b94af8b8857682542021-10-01T00:00:00Zhttps://www.mdpi.com/2076-0817/10/11/1366https://doaj.org/toc/2076-0817Viral hepatitis is one of the main causes leading to hepatocellular carcinoma (HCC). The continued rise in incidence of HCC suggests additional factors following infection may be involved. This review examines recent studies investigating the molecular mechanisms of chronic hepatitis and its association with hepatocarcinogenesis. Hepatitis B virus patients with genotype C display an aggressive disease course leading to HCC more than other genotypes. Furthermore, hepatitis B excretory antigen (HBeAg) seems to be a more sensitive predictive tumor marker exhibiting a six-fold higher relative risk in patients with positive HBsAg and HBeAg than those with HBsAg only. Single or combined mutations of viral genome can predict HCC development in up to 80% of patients. Several mutations in HBx-gene are related with higher HCC incidence. Overexpression of the core protein in HCV leads to hepatocellular lipid accumulation associated with oncogenesis. Reduced number and decreased functionality of natural killer cells in chronic HCV individuals dysregulate their surveillance function in tumor and viral cells resulting in HCC. Furthermore, high T-cell immunoglobulin and mucin 3 levels supress CD8+ T-cells, which lead to immunological dysregulation. Hepatitis D promotes HCC development indirectly via modifications to innate immunity, epigenetic alterations and production of reactive oxygen species with the LHDAg being the most highly associated with HCC development. Summarizing the results, HBV and HCV infection represent the most associated forms of viral hepatitis causing HCC. Further studies are warranted to further improve the prediction of high-risk patients and development of targeted therapeutics preventing the transition from hepatic inflammation–fibrosis to cancer.Toofan DatfarMichael DoulberisApostolis PapaefthymiouIan N. HinesGiulia ManziniMDPI AGarticleviral hepatitishepatocellular carcinomaHCCcancerrisk factorcarcinogenesisMedicineRENPathogens, Vol 10, Iss 1366, p 1366 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	viral hepatitis hepatocellular carcinoma HCC cancer risk factor carcinogenesis Medicine R
spellingShingle	viral hepatitis hepatocellular carcinoma HCC cancer risk factor carcinogenesis Medicine R Toofan Datfar Michael Doulberis Apostolis Papaefthymiou Ian N. Hines Giulia Manzini Viral Hepatitis and Hepatocellular Carcinoma: State of the Art
description	Viral hepatitis is one of the main causes leading to hepatocellular carcinoma (HCC). The continued rise in incidence of HCC suggests additional factors following infection may be involved. This review examines recent studies investigating the molecular mechanisms of chronic hepatitis and its association with hepatocarcinogenesis. Hepatitis B virus patients with genotype C display an aggressive disease course leading to HCC more than other genotypes. Furthermore, hepatitis B excretory antigen (HBeAg) seems to be a more sensitive predictive tumor marker exhibiting a six-fold higher relative risk in patients with positive HBsAg and HBeAg than those with HBsAg only. Single or combined mutations of viral genome can predict HCC development in up to 80% of patients. Several mutations in HBx-gene are related with higher HCC incidence. Overexpression of the core protein in HCV leads to hepatocellular lipid accumulation associated with oncogenesis. Reduced number and decreased functionality of natural killer cells in chronic HCV individuals dysregulate their surveillance function in tumor and viral cells resulting in HCC. Furthermore, high T-cell immunoglobulin and mucin 3 levels supress CD8+ T-cells, which lead to immunological dysregulation. Hepatitis D promotes HCC development indirectly via modifications to innate immunity, epigenetic alterations and production of reactive oxygen species with the LHDAg being the most highly associated with HCC development. Summarizing the results, HBV and HCV infection represent the most associated forms of viral hepatitis causing HCC. Further studies are warranted to further improve the prediction of high-risk patients and development of targeted therapeutics preventing the transition from hepatic inflammation–fibrosis to cancer.
format	article
author	Toofan Datfar Michael Doulberis Apostolis Papaefthymiou Ian N. Hines Giulia Manzini
author_facet	Toofan Datfar Michael Doulberis Apostolis Papaefthymiou Ian N. Hines Giulia Manzini
author_sort	Toofan Datfar
title	Viral Hepatitis and Hepatocellular Carcinoma: State of the Art
title_short	Viral Hepatitis and Hepatocellular Carcinoma: State of the Art
title_full	Viral Hepatitis and Hepatocellular Carcinoma: State of the Art
title_fullStr	Viral Hepatitis and Hepatocellular Carcinoma: State of the Art
title_full_unstemmed	Viral Hepatitis and Hepatocellular Carcinoma: State of the Art
title_sort	viral hepatitis and hepatocellular carcinoma: state of the art
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f8e9ea0d18cb43e6b94af8b885768254
work_keys_str_mv	AT toofandatfar viralhepatitisandhepatocellularcarcinomastateoftheart AT michaeldoulberis viralhepatitisandhepatocellularcarcinomastateoftheart AT apostolispapaefthymiou viralhepatitisandhepatocellularcarcinomastateoftheart AT iannhines viralhepatitisandhepatocellularcarcinomastateoftheart AT giuliamanzini viralhepatitisandhepatocellularcarcinomastateoftheart
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Viral Hepatitis and Hepatocellular Carcinoma: State of the Art

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