Hepatitis B Virus Infection: the Burden of Disease in South Africa

Hepatitis B virus infection; both acute and chronic; occurs commonly in the black population of South Africa; and chronic infection and its sequelae of cirrhosis and hepatocellular carcinoma are major public health threats. Chronic hepatitis B virus infection is rare in the other population groups; with the exception of the very small Chinese community. Prevalences of chronic carriage of hepatitis B virus in South African blacks are 5-16in rural males; 8-9in urban males; 4-12in rural females; and 2.7-4in urban females. The overall male to female ratio is 2.6:1.0. There are now three to four million South African blacks who are chronically infected with this virus. In rural black populations chronic hepatitis B virus infection is acquired very early in life; predominantly as a result of horizontal transmission of the virus; and by the age of 5 years carrier rates approach those seen in adulthood. A further slight increase occurs at school-going age and a greater increase at the time of becoming sexually active. Urban black carrier rates are significantly lower and the infection is acquired later in life. The decreased urban viral carriage rates occur mainly in the first generation born in an urban environment. Hepatitis B virus accounts for about 60of clinically evident acute viral hepatitis among blacks and about 10of chronic hepatitis and cirrhosis. It is the cause of the majority of the many cases of hepatocellular carcinoma that occur in black South Africans. The tumour is more common in males and in rural-born than in urban-born blacks. The close association between chronic hepatitis B virus infection and hepatocellular carcinoma holds true in rural and urban patients and males and females. The association is age-related; being closer in younger patients. Genotypes A and D of hepatitis B virus predominate in South African isolates; with genotype A and its subtype Aa having aparticularly high hepatocarcinogenic potential

Hepatocarcinogenic potential of genotype 5 of hepatitis C virus.

Evidence is emerging that hepatitis C virus genotypes have different carcinogenic potentials. The hepatocarcinogenicity of genotype 5, the predominant subtype in hepatitis C virus isolates in South Africa, is not known. We have compared the prevalence of genotype 5 of hepatitis C virus in 44 southern African blacks with hepatitis C virus-related hepatocellular carcinoma with that in a comparable group of patients with hepatitis C virus-induced chronic liver disease (cirrhosis or chronic hepatitis) in the absence of cancer. Hepatitis C virus serotypes 1 to 6 were identified by measuring type-specific antibodies to NS4-derived peptide antigens. Serotype 5 was present in 48% (21/44) of the patients with hepatocellular carcinoma and 37% (15/41) of those with liver disease in the absence of hepatocellular carcinoma, an insignificant difference. Although the numbers of the other genotypes were small, the differences in the prevalence rates of these serotypes between the two groups of patients were also not significant. We conclude that genotype 5 of the hepatitis C virus is neither more nor less carcinogenic than other genotypes found in isolates in South Africa.

Serum alpha-fetoprotein concentrations in urban and rural Southern African blacks with hepatocellular carcinoma.

The reason why only some hepatocellular carcinomas synthesize alpha-fetoprotein is not known. Both the frequency with which this foetal globulin is produced and the major aetiological associations of hepatocellular carcinoma vary between populations with high and low incidences of the tumour, raising the possibility that re-expression of the gene for alpha-fetoprotein is determined, or influenced by, the molecular genetic events that occur during hepatocellular carcinogenesis. This hypothesis could be tested by comparing serum alpha-fetoprotein concentrations in populations in which the major risk factors for hepatocellular carcinoma differ. Two such populations are urban and rural southern African blacks. We measured serum alpha-fetoprotein concentrations by radioimmunoassay in 234 southern African blacks with hepatocellular carcinoma: 78 of the patients were urban and they were age-matched with 156 patients born in rural areas, one-half of whom had remained in a rural environment (rural), whereas the others had migrated to the cities in adulthood (rural-urban). Urban patients were more likely than rural-born patients to have a normal serum alpha-fetoprotein value [23.1% (18/78) compared with 10.2% (16/156); p = 0.02]. There was no significant difference between the concentrations in rural and rural-urban patients. The absolute values of the raised serum alpha-fetoprotein values did not differ between urban (69,558 +/- 176,737 ng/ml; and rural-born patients (53,998 +/- 125,681 ng/ml), or between rural (69,207 +/- 159,975 ng/ml) and urban-rural patients (40,434 +/- 83,028 ng/ml). These findings are compatible with the hypothesis that re-expression of the alpha-fetoprotein gene in hepatocellular carcinoma is related to the aetiology or pathogenesis of the tumour.

The prevalence of antibodies to the hepatitis A virus in Owambo children.

The prevalence of hepatitis A virus infection, in a population as well as the age at which it is usually acquired reflect the prevailing socio-economic conditions and standards of public hygiene. Infection occurs equally in both the sexes. Black Africans are known to have a high prevalence of hepatitis A virus infection and do acquire the infection early in life. This study documents the age-specific prevalence in Owambo children and confirms an equal sex distribution.

The pathogenesis of raised serum alpha-fetoprotein levels in amoebic and pyogenic hepatic abscesses.

Serum alpha-fetoprotein (AFP) concentrations may be slightly raised in patients with amoebic hepatic abscesses. In an attempt to learn more about the pathogenesis of the raised levels, we studied 74 patients with amoebic and six with pyogenic hepatic abscesses. Serum (AFP) levels were slightly elevated (24-72 ng/ml) on admission in four patients and markedly raised (2000 ng/ml) in one, who had hepatocellular carcinoma in addition to a pyogenic hepatic abscess. The pattern of the early rise in AFP levels could not be determined because these four patients were lost to follow-up. However, serial serum AFP estimations were obtained in 29 patients with a normal value on admission and in none of these did the concentration rise during recovery. Our findings do not support the prevailing hypothesis that regenerating hepatocytes are responsible for the raised serum AFP levels in non-neoplastic hepatic disorders, including hepatic abscesses.

Membranous obstruction of the inferior vena cava and invasion of the inferior vena cava by tumour in hepatocellular carcinoma.

A 28 yr old Zulu presented with a painful swelling in the right hypochondrium and severe swelling of the legs of short duration. The serum alpha-fetoprotein concentration was over 2 X 10(5) ng/ml and imaging showed a large hepatic mass-lesion. Radionuclide venography revealed no flow through the inferior vena cava but flow through a large collateral vessel. Contrast venography showed the upper portion of the inferior vena cava to be occluded: large collateral vessels arose from the lower vena cava and the iliac veins. The histological features were those of longstanding hepatic venous outflow obstruction with irregular centrizonal and portal fibrosis: severe acute centrizonal congestion was not seen. This combination of findings indicates the presence of both membranous obstruction of the inferior vena cava, a rare developmental abnormality which predisposes to hepatocellular carcinoma formation, and invasion by the tumour of the inferior vena cava via the hepatic veins, an uncommon complication of hepatocellular carcinoma.