ADDITIVE EFFECT MODIFICATION OF HEPATITIS-B SURFACE-ANTIGEN AND E-ANTIGEN ON THE DEVELOPMENT OF HEPATOCELLULAR-CARCINOMA

To assess the role of hepatitis B e antigen (HBeAg) and its interactio n with hepatitis B surface antigen (HBsAg) on the development of hepat ocellular carcinoma (HCC), this case-control study included 361 age- a nd sex-matched pairs of patients with histologically proven HCC and he althy control subjects. HBsAg, HBeAg and antibody to HBeAg (anti-HBe) were detected by radioimmunoassay. The prevalences of HBeAg (20.2%), H BsAg (80.3%) and anti-HCV (29.5%) in cases were higher than in control s (1.9%, 20.7% and 2.7% respectively; each P<0.0001). Using patients n egative for HBsAg, HBeAg and anti-HBe as a referent group, univariate analysis indicated that HBsAg alone or HBsAg and HBeAg were risk facto rs for HCC (P for trend <0.0001). Calculation of incremental odds rati o indicated that there was additive interaction between HBsAg and HBeA g. Multivariate analysis indicated that HCC development was strongly a ssociated with the presence of HBeAg (odds ratio, 8.1; 95% confidence interval, 2.4-27.1), HBsAg (odds ratio, 68.4; 95% confidence interval, 20.5-227.8) and anti-HCV (odds ratio, 59.3; 95% confidence interval, 13.6-258.4). In conclusion, HBsAg, HBeAg and anti-HCV are independent risk factors for HCC. There is additive and independent effect modific ation between HBsAg and HBeAg on the development of HCC.