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Viruses. 2018 Oct 2;10(10). pii: E538. doi: 10.3390/v10100538.

Oncogenic Signaling Induced by HCV Infection.

Author information

1
Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France. virzi@unistra.fr.
2
Université de Strasbourg, 67000 Strasbourg, France. virzi@unistra.fr.
3
Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France. andres.roca-suarez@etu.unistra.fr.
4
Université de Strasbourg, 67000 Strasbourg, France. andres.roca-suarez@etu.unistra.fr.
5
Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France. thomas.baumert@unistra.fr.
6
Université de Strasbourg, 67000 Strasbourg, France. thomas.baumert@unistra.fr.
7
Pôle Hépato-digestif, Institut Hospitalo-universitaire, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France. thomas.baumert@unistra.fr.
8
Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France. joachim.lupberger@unistra.fr.
9
Université de Strasbourg, 67000 Strasbourg, France. joachim.lupberger@unistra.fr.

Abstract

The liver is frequently exposed to toxins, metabolites, and oxidative stress, which can challenge organ function and genomic stability. Liver regeneration is therefore a highly regulated process involving several sequential signaling events. It is thus not surprising that individual oncogenic mutations in hepatocytes do not necessarily lead to cancer and that the genetic profiles of hepatocellular carcinomas (HCCs) are highly heterogeneous. Long-term infection with hepatitis C virus (HCV) creates an oncogenic environment by a combination of viral protein expression, persistent liver inflammation, oxidative stress, and chronically deregulated signaling events that cumulate as a tipping point for genetic stability. Although novel direct-acting antivirals (DAA)-based treatments efficiently eradicate HCV, the associated HCC risk cannot be fully eliminated by viral cure in patients with advanced liver disease. This suggests that HCV may persistently deregulate signaling pathways beyond viral cure and thereby continue to perturb cancer-relevant gene function. In this review, we summarize the current knowledge about oncogenic signaling pathways derailed by chronic HCV infection. This will not only help to understand the mechanisms of hepatocarcinogenesis but will also highlight potential chemopreventive strategies to help patients with a high-risk profile of developing HCC.

KEYWORDS:

HCC; HCV; cancer; chemoprevention; liver disease; signaling

PMID:
30279347
PMCID:
PMC6212953
DOI:
10.3390/v10100538
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substance, Grant support

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