Multifactorial etiology and multifaceted prevention strategy of hepatocellular carcinoma.

In many Asian and African countries, hepatitis B virus (HBV) has been identified as a major causative agent of hepatocellular carcinoma (HCC). In these endemic areas, HBV infection also occurs early in life. An internationally collaborative study on universal immunization of newborns against HBV to prevent HCC was initiated in September 1983 and expanded later in the rural Qidong County of China, a prevalent area of both HBV infection and HCC. The 5-year follow-up data of the pilot phase of this controlled study have shown encouraging results. Over 98% of the newborns in local communities were vaccinated and over 97% of the vaccinees are being followed. The vaccination group with boosted 5-micrograms regimen showed significantly reduced HBsAg positive rate at 5 years, 2.5 vs. 12.5% of the nonvaccinated age-matched control. The anti-HBs level was also enhanced. The main study starting from the beginning of 1985 has been progressing according to schedule. Striking male preponderance and peak age shift to younger age of HCC in the high incidence area strongly points to the action of cofactors that may further increase the risk. Male preponderance was not observed in the animal models of HCC induced by hepadnaviruses. These phenomena were associated with increased exposure to aflatoxins as measured by urinary excretion of AFM1, as well as with a high prevalence of tobacco smoking and alcohol consumption among the Chinese males. The clarification of the etiological role of cofactors has important implications in the possible prevention of HCC among HBV carriers.