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.

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Membranous obstruction of the inferior vena cava has been incriminated as a risk factor for hepatocellular carcinoma in South African Blacks and in Japanese. However, the frequency with which this anomaly is found in patients with hepatocellular carcinoma, and hence its numerical importance as an etiological association of the tumor, has not been ascertained. Using radionuclide and contrast venography as well as necropsy and laparotomy examination, we investigated 162 unselected southern African Blacks with hepatocellular carcinoma together with appropriate controls for the presence of membranous obstruction of the inferior vena cava. Membranous obstruction of the inferior vena cava was detected in six of 162 (3.7%) hepatocellular carcinoma patients, compared with one of 279 subjects (0.36% p = 0.011) dying a violent death, none of 55 patients (p = 0.169) with malignant disease other than hepatocellular carcinoma and eight of 150 patients (5.3%; p = 0.336) being investigated for conditions which might have been associated with membranous obstruction of the inferior vena cava. Six of the 15 individuals (40%) found to have membranous obstruction of the inferior vena cava had concomitant hepatocellular carcinoma, confirming that membranous obstruction of the inferior vena cava constitutes a risk factor for the development of the tumor. However, only a very small proportion of hepatocellular carcinoma patients have this abnormality, so that it is a minor causal association of the tumor only.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of contraceptive steroids in the etiology or pathogenesis of hepatocellular carcinoma in urban South African black women was investigated in a hospital-based case and control study. Participating were 46 women, 19 to 54 yr old, with carcinoma, and 92 matched controls. South African blacks have a high incidence of hepatocellular carcinoma, and urban black women have used contraceptive steroids fairly widely for a number of years. Use of contraceptive steroids for longer than 6 mo (mean duration 46.7 mo) was not found to pose a risk for development of hepatocellular carcinoma in this population--relative risk 0.8 (95% confidence interval [C.I.] 0.4 to 1.7). This was also true of use for longer than 8 yr--relative risk 0.6 (95% C.I. 0.2 to 2.5), and if a combination of an estrogen and a progestogen or a progestogen alone was used (relative risk 1.7 [95% C.I. 0.7 to 4.2] and 0.4 [95% C.I. 0.1 to 1.2], respectively). Chronic hepatitis B virus infection was confirmed to have an etiological association with hepatocellular carcinoma, but there was no evidence that contraceptive steroids acted as a co-carcinogen with the virus or, conversely, that they played a causal role in patients negative for hepatitis B surface antigenemia. We cannot, however, exclude the possibility that contraceptive steroids may play a causal role in hepatocellular carcinoma in black women who have never been infected with the hepatitis B virus. Nor was there evidence that contraceptive steroids acted in concert with either cigarette smoking or chronic alcohol abuse in hepatocarcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)