Hepatocellular Carcinoma: One of the World's Most Common Malignancies

Abstract

Estimates for world and regional frequencies of hepatocellular carcinoma (HCC) vary widely However, physicians and other medical personnel practising in developing 'Third World' countries are in no doubt that this constitutes a major scourge. Furthermore, they know full well that there are few more depressing tasks than caring for a patient with this particular malignancy, for it affects young people (mostly in the third and fourth decades of life and more frequently in men) and there is no satisfactory treatment. The disease is especially common in Africa, particularly in Mozambique and Senegal, and South East Asia (1). Most tumours arise in a cirrhotic liver (when the prognosis is especially poor) and the vast majority are associated with hepatitis B virus (HBV) infections. There are several portals of entry of the virus including tattooing, ritual circumcision, scarification (often carried out by local healers or medicine men) and less frequently blood transfusion and sexual intercourse. But the most common route is by infection from the mother who is a carrier of the HBV surface antigen (HBsAg), in the immediate post-natal period. Diagnosis is usually straightforward and a large hard nodular liver, frequently with an audible bruit, is virtually confirmatory. On clinical grounds however, differentiation from an amoebic liver abscess can sometimes be difficult (1). That hepatocellular carcinoma is a common sequel of the HBsAg carrier-state is beyond question (2). Other evidence that HBV infection is usually the cause has rapidly accumulated over the last decade and can be summarised (3, 4)' (I) there is a geographical correlation between hepatocellular carcinoma and the HBsAg carrier state; (li) patients with hepatocellular carcinoma are approximately 100 times more likely to be HBsAg positive than matched controls; (iii) HBV infections precede hepatic damage and not vice versa; (iv) over a five-year period an HBsAg positive individual carries a 1000 times risk of developing hepatocellular carcinoma compared with controls; (v) chronic HBV infection often progresses to macronodular cirrhosis and then hepatocellular carcinoma (2); (vi) HBV-DNA can be detected in the hepatocellular carcinoma cell genome; (vii) experimental evidence from hepadna virus (which resembles HBV) infection in woodchucks and pekin ducks has confirmed a progression to cirrhosis and hepatocellular carcinoma. The role of non-A non-B virus infections (5) in the production of chronic liver disease is clear, but without serological markers their importance in hepatocellular carcinoma is unknown. It seems unlikely that the delta agent plays a significant part in the aetiology of hepatocellular carcinoma (6); The role of aflatoxin (a product of the fungus, Aspergilhts flavus) is still unclear (I); despite suggestive epidemiological work, mainly in Africa (a high concentration of aflatoxin B has recently been reported in millet beer in Nigeria (7)) supported by some experimental evidence, its importance is unknown. However, it has been suggested that impairment of hepatic microsomal activity (based on a background of