Increased hepatocarcinogenic potential of hepatitis B virus genotype A in Bantu‐speaking sub‐saharan Africans

Abstract

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 111 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 non-A 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.

Virological outcomes in patients infected chronically with hepatitis B virus genotype A in comparison with genotypes B and C

“…The majority of genotype A strains from our patients (86%) were found to be Ae; they were probably introduced to Japan by immigrants and visitors from foreign countries [Kobayashi et al, 2004]. Cirrhosis and hepatocellular carcinoma developed in only one of the 19 (5%) patients infected with subgenotype Ae, in remarkable contrast to frequent hepatocellular carcinoma in Africa where infection with subgenotype Aa is common during the infancy [Kew et al, 2005].…”

Novel Method for Genotyping Hepatitis B Virus on the Basis of TaqMan Real-Time PCR

“…Furthermore, genotypes A and B have been reported to be associated with an earlier seroconversion from HBeAg to anti-HBe than genotypes C and D (5,16). However, in a study from South Africa, subgenotype A1 was associated with a higher risk for HCC than other subgenotypes of A or non-A genotypes (14). Genotype impact on treatment outcome is more uncertain, but genotype B has been shown to respond better to alpha interferon treatment than genotype C (13,30).…”

Variations and mutations in the hepatitis B virus genome and their associations with clinical characteristics

“…HBV/A is mainly distributed in Africa (HBV/A1), the United States of America, and Europe (HBV/A2). Several reports from Africa, India, and Brazil have shown that HBV/A1 is associated with a high incidence of HCC in younger patients without cirrhosis [22] . By contrast, HBV/A2 is reported to be associated with a lower incidence of HCC than HBV/D and HBV/ F [23,24] .…”