Aetiological factors in hepatocellular cancer

The major risk factors for HCC are outlined in Table 2. Each factor may contribute to the multistep process of hepatocarcinogenesis. Hepatitis B virus and aflatoxins are the principal aetiological candidates and may be considered as initiators of the malignant state (see Figure 1). The majority of HCC arises via the cirrhotic pathway; the associated changes in the hormonal milieu may alter the handling of environmental carcinogens and the rounds of cell proliferation may increase sensitivity to sub-threshold doses of carcinogens. Exogenous androgens and oestrogens may operate through a similar mechanism to promote clonal expansion of preneoplastic cells. The importance of identifying the major aetiological factors lies in the possibility of prevention. The prognosis of HCC is dismal and it represents a major scourge in developing Third World countries. It is encouraging to think that the majority of cases could be prevented by the widespread use of hepatitis B vaccines and the development of intervention programmes against aflatoxin contamination of foodstuffs.