John Hodkinson

The Relative Roles of Hepatitis B and C Viruses in the Etiology of Hepatocellular Carcinoma in Southern African Blacks

BACKGROUND & AIMS Epidemiological studies have shown the relative roles of hepatitis B and C viruses in hepatocarcinogenesis to vary considerably among populations. The aim of this study was to define the independent and interactive roles of the two viruses in the genesis of hepatocellular carcinoma in southern African blacks. METHODS Blood samples were taken from 231 black patients with hepatocellular carcinoma and matched controls treated at four Johannesburg hospitals. These were tested for hepatitis B surface antigen, antibodies to hepatitis C virus, and hepatitis C virus RNA. RESULTS Relative to individuals without serological evidence of hepatitis B or C infection, those positive for hepatitis B surface antigen alone had a statistically significant 23.3-fold increased risk for hepatocellular carcinoma, whereas those positive for hepatitis C serology alone had a statistically significant risk of 6.6. A synergistic effect on risk was evident when both hepatitis B and C markers were present (relative risk, 82.5). Hepatitis B virus alone is estimated to cause 43% of hepatocellular carcinoma in southern African blacks, hepatitis C alone 5%, and coinfection with the two viruses 20%. CONCLUSIONS Hepatitis B virus plays a predominant role in hepatocellular carcinogenesis in southern African blacks, with hepatitis C virus responsible for a smaller proportion of cases. Coinfection with the two viruses carries a synergistic risk of hepatocellular carcinoma formation.

249serp53 mutation in the serum of black southern African patients with hepatocellular carcinoma

Background and Aims:  A specific mutation at codon 249 of the p53 tumor suppressor gene (guanine to thymine; arginine to serine [249serinep53]) is present in the cell‐free plasma of 30–47% of patients with hepatocellular carcinoma (HCC) in regions with uniformly high levels of dietary exposure to the fungal toxin, aflatoxin B1. No information is available from other regions. We therefore examined cell‐free serum from HCC patients in southern Africa, where aflatoxin B1 exposure ranges from very high to low levels.

Serum vitamin B12 binders in south african blacks with hepatocellular carcinoma

Sera from 242 South African blacks with hepatocellular carcinoma were assayed for unsaturated vitamin B12 binding capacity (UBBC) and vitamin B12 activity. Six patients were younger than 20 years of age, and 24% were younger than 30 years of age. Eighty‐four percent of the patients had a slightly raised UBBC and 86% had a slightly elevated vitamin B12 value, but in no patient was an exceptionally high UBBC present. Serum UBBC and vitamin B12 were not higher in younger patients, and raised UBBC values were not related to serum alpha‐fetoprotein values. Serum UBBC and vitamin B12 concentrations were not significantly different in patients with and without coexisting cirrhosis. In none of the patients with a UBBC above 3000 pg/ml was the fibrolamellar variant of hepatocellular carcinoma present. The authors conclude that South African blacks with hepatocellular carcinoma do not secrete an abnormal vitamin B12 binding protein.

Non‐specificity of messenger RNA of α‐fetoprotein in peripheral blood in detecting early spread of hepatocellular carcinoma in black Africans

Awareness of early spread of hepatocellular carcinoma is crucial in selecting patients for surgical intervention. α‐Fetoprotein is widely used as a serum marker for hepatocellular carcinoma. Our aim was to evaluate the specificity of α‐fetoprotein‐mRNA transcription in cells in the peripheral blood for diagnosing early spread of hepatocellular carcinoma in black Africans. α‐Fetoprotein‐, albumin‐ and prothrombin‐mRNA were detected in peripheral blood mononuclear cells by reverse transcription‐polymerase chain reaction. α‐Fetoprotein‐mRNA was shown in peripheral blood mononuclear cells in 53% (35/66) of patients with hepatocellular carcinoma, but also in 45% (10/22) of healthy blacks, 64% (14/22) of black patients with acute hepatitis, 55% (11/20) of those with chronic hepatitis or cirrhosis and 75% (9/12) of those with hepatic metastases (from a number of primary sites). Specificity of albumin‐ and prothrombin‐mRNA was better than that of α‐fetoprotein‐mRNA, although the sensitivity was reduced. The corresponding prevalence of albumin‐mRNA for each group of patients or controls was 30% (20/66), 9% (2/22), 41% (9/22), 10% (2/20), and 17% (2/12), respectively, and for prothrombin‐mRNA 27% (18/66), 4.5% (1/22), 27% (6/22), 20% (4/20) and 17% (2/12), respectively. We conclude that the non‐specificity of α‐fetoprotein‐mRNA transcription in peripheral blood in recognizing malignant hepatocytes in the circulation severely limits its usefulness in diagnosing the early spread of hepatocellular carcinoma in black Africans.