The role of hepatitis B virus integrations in the pathogenesis of human hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer death world wide, accounting for approximately 600,000 deaths per year [1–4]. In North America, Western Europe and Australia the annual incidence of HCC is less than 4/100,000 per year, compared to incidence rates of up to 50/100,000 per year in parts of sub-Saharan Africa and South East Asia [1]. There is a male gender predominance in HCC incidence; the worldwide age standardized incidence rate for men is 15.8/100,000 per year while for women it is 5.8/100,000 per year [1,4]. The geographical and gender differences in the incidence rate of HCC may be due to genetic and physiologic differences as well as to the variable prevalence of risk factors such as cirrhosis due to chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection or co-infection, alcoholic cirrhosis, hemochromatosis, and exposure to dietary aflatoxin [5–11]. Chronic HBV infection is one of the most important risk factors for HCC development [12,13]. There is a high rate of HBV infection worldwide, with an incidence over 50 million new cases a year and a prevalence of over 350 million HBV surface antigen positive chronic carriers. There is significant geographic variability in the rates of chronic HBV infection. In many high-prevalence countries in Africa and Asia most infected individuals acquire the infection perinatally or during early childhood. Many of these persons develop immune tolerance to the virus and have lifelong chronic infection. About 90% of infants infected during the first year of life and 30–50% of children infected between 1 and 4 years of age develop chronic infection. The lifetime risk of death from HBV-related liver cancer or cirrhosis is approximately