Hepatitis C virus: from oxygen free radicals to hepatocellular carcinoma.
Epidemiological evidence clearly identifies chronic infection with hepatitis C virus (HCV) as a major risk factor for the development of hepatocellular carcinoma (HCC). Among the mechanisms that have been implicated in the pro-carcinogenic effect of HCV infection, an increased production of reactive oxygen species in the liver seems to have a major pathogenetic role in leading from chronic inflammation to cancer. Recent data have also demonstrated that HCV is capable of inducing this active production of free radicals per se, not just through inflammation, a feature peculiar to this virus and the specific activity of its core protein. This paper provides an overview of the inter-relationships between HCV, liver damage, free radical production and HCC, describing at least in part the complex network involving DNA oxidative damage, cytokine synthesis, proto-oncogene activation and oestrogen receptor expression, that may all be deeply involved in liver carcinogenesis.
Farinati
F
F
Dipartimento di Scienze Chirurgiche e Gastroenterologiche, Sezione di Gastroenterologia, Policlinico Universitario, Università di Padova, Padova, Italy. fabio.farinati@unipd.it
Cardin
R
R
Bortolami
M
M
Burra
P
P
Russo
F P
FP
Rugge
M
M
Guido
M
M
Sergio
A
A
Naccarato
R
R
D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000378:metabolism* / Q000821:virology; D016207:Cytokines / Q000378:metabolism*; D004249:DNA Damage; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D016174:Hepacivirus / Q000378:metabolism* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000150:complications / Q000378:metabolism / Q000821:virology*; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications / Q000378:metabolism* / Q000821:virology; D000090063:Proto-Oncogene Mas; D017382:Reactive Oxygen Species / Q000378:metabolism*
D016207:Cytokines; D012739:Gonadal Steroid Hormones; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D017382:Reactive Oxygen Species