Hepatitis B virus, alpha-fetoprotein synthesis, and hepatocellular carcinoma in Zaire

We investigated the epidemiology of hepatocellular carcinoma (HCC) in Zaire, and evaluated the association between exposure to hepatitis B virus (HBV) and the development of HCC. Two hundred and twenty-three consecutive cases of HCC diagnosed over 19 years (1966-1985) were reviewed. HCC represented 8.32% of all carcinomas and 5.56% of all cancers. Frequency was higher in males (75.7%) than in females (24.3%); a sex ratio of 3/1. The majority (82.1%) of patients were aged 14 to 55 years with a peak occurrence in the fourth decade (28.6%). The mean age in males (41.27 +/- 17.5 years) and females (37.40 +/- 15.16 years) was significantly different (p < 0.02). Sera from 40 patients and 68 age and sex-matched controls were analyzed for markers of HBV infection: patients and controls had comparable rates of exposure (96% vs 72.1%, respectively). However, patients had significantly higher HBsAg carrier rates (56.7% vs 7.35%; p < 0.001), and lower anti-HBsAg seroconversion rates (25% vs 63.2%, p < 0.05). Using immunohistochemical analysis, the livers of patients were evaluated for HBsAg and HBcAg. These HBV antigens were more frequent in non-tumourous hepatocytes (53.3% vs 23.3%, respectively) than in HCC cells (13.3% vs 3.3%). Serum alpha-fetoprotein (AFP) was abnormal (> 20 ng/ml) in 90% of patients. The geometric mean (GM) AFP was 7273.8 ng/ml. AFP levels were significantly higher in HBsAg-positive HCC cases (GM: 19,322.6 ng/ml; 95% confidence interval (CI): [3639.2, 102,565.2]) than in antigen negative cases (GM: 1939.5 ng/ml; 95% CI: [182.8, 19,952.6]), but did not correlate with HBV replication. Immunohistochemical detection of AFP revealed a similar correlation between AFP and HBsAg. Neither AFP level nor HBsAg production correlated with cellular atypia or tumor grade.