Cancer Research UK : Hepatitis viruses and cancer

Hepatitis viruses and cancer

This section contains information on hepatitis viruses, including Hepatitis B and Hepatitis C.

Chronic infection with hepatitis B and C causes 75-80% of liver cancers diagnosed world-wide1. Figure 6.1 shows international variation in the prevalence of these viruses in human populations. High prevalence areas are also those with the highest incidence rates for liver cancer. Other causes of the disease include liver damaging agents, such as alcohol, which become more important in countries such as where hepatitis virus infection is less prevalent.

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Hepatitis B virus

Hepatitis B virus (HBV), an agent that specifically infects and replicates in liver cells, is highly prevalent in many areas of the world, especially in South East Asia and sub-Saharan Africa. This not only explains the high rates of hepatitis (inflammation of the liver) in these populations but is very likely to be responsible for their increased incidence of primary liver cancer1. Thus chronic HBV carriers have a 20-100-fold higher risk of liver cancer than uninfected individuals. Tumours tend to arise after 30 years or more of chronic HBV infection and the great majority show evidence of clonally integrated HBV DNA sequences in the tumour cells2, 3.

Such evidence strongly suggests a causative role for HBV in liver carcinogenesis, but the precise mechanism through which HBV acts is still not understood. In most cases the HBV genome is not integrated near cellular oncogenes and although some HBV proteins have interesting effects on cell growth in the laboratory, the virus does not consistently express those viral proteins when it is present in tumour cells. A more likely scenario is that many virus-infected liver cells are destroyed as a result of immunological attack rather than by virus replication per se. Such damage stimulates the remaining cells to grow and divide, thereby increasing the risk of genetic accidents. In addition, subsequent infection of regenerating cells can lead to chance integration of viral DNA into their genome, further promoting cell genomic instability (see Figure 6.2 (A)).

Figure 6.2: Cell transformation by DNA viruses: Basic mechanisms

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Together these effects would enhance the chances of a HBV-infected liver cell accumulating the series of genetic changes necessary for its malignant conversion (Figure 6.3). Other co-factors may act independently of HBV; evidence suggests that one such co-factor might be the presence in the diet of certain carcinogenic chemicals arising from the use of poorly preserved foodstuffs4.

Figure 6.3: Hepatitis B virus and liver cancer

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Hepatitis C virus

In contrast to HBV, which may act through a combination of direct and indirect mechanisms, the infection of the liver with hepatitis C virus (HCV), is thought to increase the risk of liver cancer by purely indirect means. World-wide, 0.5 to 2% of the population have current or past infection with hepatitis C. Despite the similarity in name, HCV is quite different from HBV; it is an RNA virus and never converts its genome into a DNA copy, and so there is no risk of integrating viral sequences accidentally into the cell genome. However, like HBV, it damages liver cells and causes continual re-growth (see Figure 6.3, step 2); this alone is enough to increase the risk of genetic accidents leading to liver cancer. There is also an increased risk of non-Hodgkin lymphoma (NHL) among people infected with hepatitis C; the mechanism underlying this association is still not understood5, 6.

References for Hepatitis viruses and cancer

IARC, IARC Monograph on the evaluation of carcinogenic risks to Humans Volume 59. Hepatitis viruses. ed., ed. Vol. 1994, Lyon.
Buendia, M., Hepatitis B viruses and hepatocellular carcinoma. Adv Cancer Res, 1992. 59: p. 167-226.
Levy, L., et al., Genetic alterations and oncogenic pathways in hepatocellular carcinoma. Ann N Y Acad Sci, 2002. 963: p. 21-36.
Henry, S.H., F.X. Bosch, and J.C. Bowers, Aflatoxin, hepatitis and worldwide liver cancer risks. Adv Exp Med Biol, 2002. 504: p. 229-233.
Mazzaro, C., U. Tirelli, and G. Pozzato, Hepatitis C virus and non-Hodgkin lymphoma 10 years later. Dig Liver Dis, 2005. 37(4): p. 219-226.
Libra, M., D. Gasparotto, and A. Gloghini, Hepatitis C virus (HCV) 1 and hepatitis C virus (HCV) infection and lymphoproliferative disorders. Front Biosci, 2005. 10: p. 2460-2471.