Hepatitis B e Antigen and the Risk of Hepatocellular Carcinoma

To the Editor: Yang et al. (July 18 issue)¹ report that the detection of hepatitis B e antigen (HBeAg) at a single point in time during the course of chronic hepatitis B predicts the development of hepatocellular carcinoma. As noted in the article and the accompanying editorial,² there are no hints of the direct involvement of HBeAg in the mutagenicity in the liver. On the other hand, HBeAg represents a surrogate marker of viral replication and necroinflammatory activity. The authors discuss both direct mechanisms of carcinogenicity (hepatitis B x antigen [HBxAg]–related effects) and indirect mechanisms of carcinogenicity (chronic hepatic inflammation . . .