Chronic hepatitis B infection is denoted by the persistence of hepatitis B surface antigen (HBsAg) in the serum and is known to be a significant risk factor for cirrhosis and hepatocellular carcinoma. Previous research has demonstrated that the presence of hepatitis B envelope antigen (HBeAg), in addition to HbsAg, is a marker for active viral replication, but there are conflicting results in retrospective studies about the subsequent risk for hepatocellular carcinoma. Yang and colleagues reported on a prospective, population-based study of HBsAg and HBeAg seroprevalence and the subsequent risk of hepatocellular carcinoma.

The authors invited 47,079 men between 30 to 65 years of age from seven different townships in Taiwan to participate in the study. Informed consent was obtained from 25 percent of the men, and 11,893 subjects without hepatocellular carcinoma were followed for nine years. Serum testing for HBsAg, HBeAg, and hepatitis C antibody was performed at study entry. Subsequent cases of hepatocellular carcinoma were ascertained by death certificate review or entry in a nationwide cancer registry. HBsAg positivity was seen in 19 percent of men, of whom 39 percent were also positive for HBeAg. A total of 111 cases of hepatocellular carcinoma developed during the study follow-up.

After adjusting for hepatitis C infection, smoking, alcohol use, age, and sex, the relative risk for hepatocellular carcinoma was 9.6 in men with HBsAg seropositivity alone, and it jumped to 60.2 when both HBsAg and HBeAg were present, compared with subjects who were seronegative for both markers.

The authors concluded that the presence of HBeAg in addition to HBsAg seropositivity greatly increased the risk for development of hepatocellular carcinoma.