Hepatocellular carcinoma (HCC) is the most common cancer in The Gambia. Hepatitis B virus (HBV) infection is endemic, with 15% to 20% of the population being chronic carriers, whereas hepatitis C virus (HCV) prevalence is low. We recruited 216 incident cases of HCC and 408 controls from three sites. HBV carriage was present in 61% (129/211) of HCC patients and 16% (64/402) of controls, whereas 19% (36/191) of HCC patients were HCV seropositive compared with 3% (11/382) of controls. HCC patients with HCV were notably older and were more likely to be female than those with HBV. Increased HCC risk was strongly associated with chronic HBV (odds ratio, 16.7; 95% CI, 9.7-28.7), HCV (16.7; 6.9 -40.1), and dual infection (35.3; 3.9 -323). We interpret the additive nature of risk with coinfection as representative of HBV and HCV acting primarily through shared steps in the multistage process of hepatocarcinogenesis. HCV infection was not observed among younger participants, suggesting a possible cohort effect. Reasons for the striking age and gender differences in HCC associated with HBV compared with HCV are unclear, but transmission patterns and age at exposure may be factors. In conclusion, in a standardized evaluation of well-characterized study participants from The Gambia, most cases of HCC are attributable to HBV (57%), but HCV adds a significant fraction (20%), especially among older patients and females. If HCV transmission is not perpetuated in future cohorts, focusing available resources on HB vaccination efforts could greatly ameliorate a major cause of cancer death in sub-Saharan Africa. (HEPATOLOGY 2004;39:211-219.) H epatitis B virus (HBV) and hepatitis C virus (HCV) infections are established causes of hepatocellular carcinoma (HCC). 1 Despite decades of experimental and epidemiologic investigation and widespread acceptance of their carcinogenicity, the specific mechanisms by which they lead to HCC and the effect of coinfection with HBV and HCV remain poorly understood.
Geography plays an important role, whereby variation in the epidemiologic patterns of infection and the corresponding HBV and HCV prevalence crudely reflects HCC incidence patterns. 2,3 The greatest burden of HCC is in sub-Saharan Africa and parts of Asia, where HCC is the most frequent cause of cancer death among men. 2 Chronic HBV infection is highly prevalent and is the predominant risk factor for HCC in these high-incidence regions. [2][3][4] The United States and Europe have much lower HCC rates, with increases in recent years attributed to HCV infection. 5,6 The age of onset of HCC is much younger in Africa and Asia, with a median of 40 to 50 years compared with 55 to 65 years in the United States (see Fig. 1). The male-to-female ratio of HCC cases is