Hepatitis B virus-related hepatocarcinogenesis: molecular oncogenic potential of clear or occult infections.

Chronic viral infection is the most important oncogenetic factor, and hepatitis B virus (HBV) plays an important role in the development of hepatocellular carcinoma (HCC). HBV-related carcinogenesis is a multi-step process, encompassing the combination of different, not mutually exclusive effects such as the induction of chronic liver inflammation and regeneration, its integration into the hepatocyte genome and the transactivating and transforming activity of several viral proteins (HBx and truncated Pre-S2/S) that may stimulate cellular oncogenes or suppress growth-regulating genes. Data related to the influence of different hepatitis B virus genotypes and the emergence of selective variants as biomarkers of HCC development still remain controversial.

Evolution of hepatitis C virus non-structural 5A gene in the progression of liver disease to hepatocellular carcinoma.

Background: The interaction between the hepatitis C virus (HCV) non-structural 5A (NS5A) protein of HCV and the protein kinase R (PKR), which is an effector of the cellular antiviral response and has been defined as a tumour suppressor, may affect the control of protein synthesis and cell growth.

Aim: We investigated the genetic evolution of the NS5A region in the NS5A PKR-binding domain (NS5A-PKRbd) of patients with HCV 1b-related cirrhosis who subsequently developed or not hepatocellular carcinoma (HCC).

Patients And Methods: The quasispecies composition of NS5A-PKRbd was inferred by sequencing an average of 15 clones per sample in specimens obtained from 26 patients with cirrhosis who developed or not HCC during a follow-up of 5 years.

Prevalence of wild-type in NS5A-PKR protein kinase binding domain in HCV-related hepatocellular carcinoma.

Background/aims: Experimental studies have demonstrated that the wild-type PKR-NS5A strain of hepatitis C virus (HCV) may have oncogenic potential through the binding and functional repression of PKR protein kinase. To assess whether the NS5A-PKR-binding domain may be involved in HCV-related liver carcinogenesis, its sequence was analyzed in the sera of 85 patients with hepatocellular carcinoma (HCC) and in 51 patients with chronic active hepatitis (CAH). In 13 HCC cases sequence analysis was also performed in tumor and nontumor liver tissues.