Hepatitis C Virus as a Causative Agent of Hepatocellular Carcinoma

Abstract

HCV infection has shown to be strongly linked to the development of hepatocellular carcinoma in epidemiological studies. However, the mechanism of carcinogenesis by HCV is poorly understood. Unlike other human oncogenic viruses, HCV is a typical RNA virus, and thus there is no integration of the viral genome or a piece of the genome into host chromosomes. Moreover, transacting transcriptional factors which are coded by other human oncogenic viruses and required primarily for virus replication and often involved in cell immortalization, may not be coded by HCV. Although regeneration of hepatocytes in an HCV-infected liver may be of primary importance in driving hepatocytes to the malignant stage, an additional unknown carcinogenic function of HCV may also exist. For this reason, clarification of the molecular mechanism of virus replication in hepatocytes should be emphasized.

Activation of the interferon-inducible protein kinase PKR by Hepatocellular carcinoma derived-Hepatitis C virus core protein

“…Hepatitis C virus (HCV) infection is highly prevalent world-wide and is characterized by a very high rate (70 ± 80%) of progression to a chronic carrier state, as well as a risk of developing liver cirrhosis and hepatocellular carcinoma (HCC) (Lai and Ware, 2000;Shimotohno, 1995Shimotohno, , 2000. The molecular basis for the frequent resistance of HCV to interferon a (IFNa) therapy is poorly understood (see reviews in Brechot, 1998;McHutchison and Poynard, 1999;Sarrazin and Zeuzem, 1999).…”

“…Hepatocellular carcinoma is a long term complication of HCV infection, the tumor developing about 10 ± 20 years after acute infection as a complication of liver cirrhosis (see review in Shimotohno, 1995Shimotohno, , 2000. Chronic liver in¯ammation and ®brosis, the major histological features of chronic active hepatitis and cirrhosis, are major mechanisms of HCV-related liver carcinogenesis; there is also some evidence for a direct modulation of liver cell viability and proliferation by HCV protein expression, such as the viral core, E2 NS3 and NS5A proteins (reviews in Lai and Ware, 2000;McLauchlan, 2000;Tsuchihara et al, 1999, Neddermann et al, 1997.…”

Hepatitis C virus core protein binds to apolipoprotein AII and its secretion is modulated by fibrates

“…1 Persistent HCV infection, which develops in at least 70% to 80% of infected patients, often progresses to chronic hepatitis and is highly correlated with the development of cirrhosis and hepatocellular carcinoma. [2][3][4] Neither a vaccine, nor effective therapy are currently available for HCV, other than interferon alfa combined with ribavirin. 5,6 HCV is an enveloped virus belonging to the Flaviviridae family.…”

Hepatitis C Virus Core Protein Interacts with Heterogeneous Nuclear Ribonucleoprotein K

“…Hepatitis C Virus (HCV) 1 is the major cause of transfusionand community-acquired non-A, non-B hepatitis (1)(2)(3), often leading to cirrhosis of the liver, hepatocellular carcinoma (3)(4)(5), and some autoimmune diseases (6 -10). HCV is an enveloped, single-stranded, positive-sensed RNA virus.…”