The first suggestion that the hepatitis B virus (HBV) might be related causally to genesis of human hepatocellular carcinoma (HCC) was made by Payet et al. (1956). Subsequently it was recognized that chronic viral hepatitis was a frequent sequela of HBV infection on the basis of the identification of viral surface antigens in patients with chronic viral hepatitis. Today it is estimated that there are nearly 300 million individuals chronically infected with HBV. A map indicating the areas where infection predominates is seen in Figure 12.12 (IARC, 1994a). Gen- erally speaking, the highest incidence of HCC is also found in the areas exhibiting the highest incidence of chronic HBV hepatitis (Melnick, 1983). Furthermore, almost every patient with HCC in highly endemic areas (but not in the United States) exhibits serological and virological evidence of hepatitis B infection. Since it is not possible to eliminate chronic infection com- pletely and the incubation period for the development of HBV-associated HCC may be as long as 30 years, the potential incidence of HCC as a result of this chronic infection is very high, approaching 40% in some areas (cf. Chisari and Ferrari, 1995). Today liver cancer ranks sixth of the most common, potentially fatal cancers in the world (Chapter 1). The reason for these dis- tinctive differences in incidence of HBV infection and HCC is seen diagrammatically in Figure 12.13. In several Asian countries, notably Taiwan, hepatitis B is frequently passed from mother to infant, resulting in very early infections; almost all of these infants subsequently become
Figure 12.12 Geographical pattern of the prevalence of hepatitis B infection in the humans. Black:
≥8%, high; gray: 2% to 7.9%, intermediate; white: <2%, low. (From IARC Monograph 59, 1994, with permission of the publisher.)
chronic carriers. A similar phenomenon occurs in African countries, although the mode of initial transmission is not clear. In nonendemic countries, such as the United States and many European countries, the primary infection that occurs later in life seldom results in the chronic carrier state. HCC is a relatively unusual sequela of the carrier state in nonendemic areas; but in en- demic areas such as Taiwan and parts of mainland China, the risk for developing HCC is 200- fold greater than in uninfected individuals (Buendia, 1992). This risk may be increased as much as eightfold if the infected individual is chronically exposed to aflatoxin B1 as a contaminant in
the diet (cf. Groopman et al., 1996). Vaccines against HBV are now readily available but some-what expensive. Thus far, extensive vaccination programs have not been carried out in most countries with the exception of Taiwan, where there is evidence of the prevention of cancer by the vaccine when it is administered to children (cf. Wild and Hall, 1999).