Hcv As A Hepatocarcinogen

Evidence for a causal role for HCV, a single-stranded RNA virus belonging to the Flaviviridae, in HCC is more recent but almost equally compelling. In common with HBV infection, the importance of chronic HCV infection as a risk factor for the tumor differs between developed and developing countries (74,75). In the former, whatever the incidence of HCC, HCV is a more important causal association of the tumor than is HBV, and in Japan, Italy, and Spain the virus accounts for as much as 80% of HCCs (74,75). For patients in these countries who have been referred to a hepatology clinic with chronic HCV infection, the annual risk of developing HCC ranges from 1.0% to 8.9%, with the risk being greater both in countries with higher incidences of the tumor and in patients with cirrhosis than in those with chronic hepatitis. Persistent HCV infection and alcohol abuse often (and chronic HBV infection and alcohol abuse less often) coexist as causal associations of HCC in developed countries (74,75). HCV plays a secondary role in the genesis of HCC in ethnic Chinese and black African populations, in which HBV is the dominant risk factor.

Patients with HCV-related HCC are generally older than those with HBV-induced tumors, especially in developing countries where the difference in mean age may be as much as 20 yr (74,75). The interval between initial infection with the virus and the diagnosis of HCC is generally 25-30 yr, although a few patients present in as short a time as 5-10 yr. Controversy exists over whether HCV genotype 1b is more closely associated with HCC than the other genotypes and whether treatment of chronic hepatitis C infections with interferon-a lessens the risk of neoplastic supervention (75).

Mechanisms of Carcinogenicity

Almost all HCV-related HCCs arise in cirrhotic livers and most of the remainder develop against a background of chronic hepatitis, an observation that strongly suggests that chronic necroinflammatory hepatic disease is an important contributor to the development of the tumor (74,75). HCV replicative intermediates do not integrate into chromosomal DNA, but apart from this the mechanisms whereby an increased hepatocyte turnover rate may act as a tumor promoter already mentioned in respect to HBV would apply equally or to an even greater extent to HCV. An important pathogenetic role for chronic necroinflammatory hepatic disease offers one explanation for the frequent coexistence of HCV infection and alcohol abuse in patients with HCC, the two factors combining to induce more severe degrees of hepatocyte necrosis and regeneration.

The possibility that HCV could also be directly carcinogenic was initially suggested by the observation that a few HCV-related tumors arose in normal or near normal livers (76). More convincing evidence was provided by the recent report that transgenic mice in which the core gene together with its regulatory sequences have been introduced develop HCC (77). HCV would have to exert its direct carcinogenic effect from an extrachrosomal position, and possible mechanisms have been proposed. The deduced amino acid sequence of the HCV core protein shows it to be a basic protein that contains a putative DNA binding motif, as well as triplicate nuclear localization signals and several putative protein kinase A and C recognition sites (78,79). These characteristics imply that the protein could function as a gene-regulatory protein. The nonstructural NS3 protein has both proteinase and helicase activity. NIH 3T3 cells transfected with the 5' half of the HCV sequence encoding NS3 proliferated rapidly, lost contact inhibition, grew anchorage-independently in soft agar, and formed tumors in nude mice (80). HCV replication may mediate the coexpression of TGF-a and insulin-like growth factor II, resulting in uncontrolled cell proliferation (81).

A positive interaction between the carcinogenic effects of HBV and HCV has been demonstrated in the majority but not all populations that have been studied (82). This interaction has usually taken the from of a multiplicative effect. An interactive effect between excessive iron and persistent HCV infection has also been suggested. In the only study addressing this question, however, no correlation could be demonstrated between tissue iron and HCV (or HBV) infection (83).

Beat The Battle With The Bottle

Beat The Battle With The Bottle

Alcoholism is something that can't be formed in easy terms. Alcoholism as a whole refers to the circumstance whereby there's an obsession in man to keep ingesting beverages with alcohol content which is injurious to health. The circumstance of alcoholism doesn't let the person addicted have any command over ingestion despite being cognizant of the damaging consequences ensuing from it.

Get My Free Ebook

Post a comment