Relation between hepatocellular carcinoma and persistent hepatitis B infection.

Epidemiologic studies indicate a close association between hepatocellular carcinoma (HCC) and chronic hepatitis B virus (HBV) infection. HCC, a most frequent malignancy, is far more common in the Far East and Africa than in the West and may be the first to be greatly eliminated because of prevention of HBV infection by vaccination. The conceptual integration of epidemiologic observations, morphologic studies of the human precursor stages and investigations of animal infections by hepadna viruses with biologic and genomic similarity to HBV as well as with clinical and molecular biologic studies contribute to the understanding of the hepatocarcinogensis. In the woodchuck model after laboratory infection, HCC develops regularly without external cocarcinogen in permanent surface antigen carriers. The hypothesis is presented that an episodic necroinflammation in the carrier stage may act as an endogenous cocarcinogen or promoter in that previous integration of hepadna viral DNA in the host chromosone may become disorganized, which induces the clonal development of HCC. This hypothesis may become important in the management of the carrier stage.