Increased hepatocarcinogenic potential of hepatitis B virus genotype A in Bantu-speaking sub-Saharan Africans

Genotypes A, D, and E of the hepatitis B virus (HBV) circulate in southern Africa, with genotype A predominating. Their hepatocarcinogenic potential in Bantu-speaking sub-saharan Africans is, however, unknown. Using a case/control format, we investigated the hepatocarcinogenic potential of these genotypes and subgenotype A1 of genotype A, which accounts for the great majority of genotype A isolates. HBV isolates from 111 unselected Bantu-speaking sub-saharan Africans with hepatocellular carcinoma (HCC) and ill matched asymptomatic chronic carriers, serving as controls, were genotyped using the method of [Lindh et al. (1997): J Infect Dis 175:1285-1293]. Subgenotypes of genotype A were determined using an in-house restriction fragment length polymorphism assay. Genotype A was present in 96 (86.5%) of patients with HCC and 76 (68.5%) of the carriers, giving a 4.5-fold (95% confidence limits: 1.86, 10.90) increased risk of HCC in carriers infected with genotype A compared with those infected with non-A genotypes. HCC patients infected with genotype A were significantly younger than those infected with non-A genotypes (P=0.02). The distributions between these two groups according to sex, geographic background, and tribe were not significantly different. Subgenotype A1 was present in all of the 77 cancer patients and 69 of 70 carriers analyzed, yielding a relative risk of 4.21 (95% confidence limits: 1.73,10.23) of HCC in those infected with subgenotype A1 compared with those infected with nonA genotypes. Genotype A has a greater hepatocarcinogenic potential than non-A genotypes in Bantu-speaking sub-saharan Africans and this is entirely attributable to subgenotype A1.