Yang Hwai-I, Lu Sheng-Nan, Liaw Yun-Fan, You San-Lin, Sun Chien-An, Wang Li-Yu, Hsiao Chuhsing K, Chen Pei-Jer, Chen Ding-Shinn, Chen Chien-Jen
Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei.
N Engl J Med. 2002 Jul 18;347(3):168-74. doi: 10.1056/NEJMoa013215.
The presence of hepatitis B e antigen (HBeAg) in serum indicates active viral replication in hepatocytes. HBeAg is thus a surrogate marker for the presence of hepatitis B virus DNA. We conducted a prospective study to determine the relation between positivity for hepatitis B surface antigen (HBsAg) and HBeAg and the development of hepatocellular carcinoma.
In 1991 and 1992, we enrolled 11,893 men without evidence of hepatocellular carcinoma (age range, 30 to 65 years) from seven townships in Taiwan. Serum samples obtained at the time of enrollment were tested for HBsAg and HBeAg by radioimmunoassay. The diagnosis of hepatocellular carcinoma was ascertained through data linkage with the computerized National Cancer Registry in Taiwan and with death certificates. We performed a multiple regression analysis to determine the relative risk of hepatocellular carcinoma among men who were positive for HBsAg alone or for HBsAg and HBeAg, as compared with those who were negative for both.
There were 111 cases of newly diagnosed hepatocellular carcinoma during 92,359 person-years of follow-up. The incidence rate of hepatocellular carcinoma was 1169 cases per 100,000 person-years among men who were positive for both HBsAg and HBeAg, 324 per 100,000 person-years for those who were positive for HBsAg only, and 39 per 100,000 person-years for those who were negative for both. After adjustment for age, sex, the presence or absence of antibodies against hepatitis C virus, cigarette-smoking status, and use or nonuse of alcohol, the relative risk of hepatocellular carcinoma was 9.6 (95 percent confidence interval, 6.0 to 15.2) among men who were positive for HBsAg alone and 60.2 (95 percent confidence interval, 35.5 to 102.1) among those who were positive for both HBsAg and HBeAg, as compared with men who were negative for both.
Positivity for HBeAg is associated with an increased risk of hepatocellular carcinoma.
血清中乙肝e抗原（HBeAg）的存在表明肝细胞中有活跃的病毒复制。因此，HBeAg是乙肝病毒DNA存在的替代标志物。我们进行了一项前瞻性研究，以确定乙肝表面抗原（HBsAg）和HBeAg阳性与肝细胞癌发生之间的关系。
1991年和1992年，我们从台湾七个乡镇招募了11893名无肝细胞癌证据的男性（年龄范围为30至65岁）。入组时采集的血清样本通过放射免疫测定法检测HBsAg和HBeAg。通过与台湾计算机化的国家癌症登记处和死亡证明进行数据关联来确定肝细胞癌的诊断。我们进行了多元回归分析，以确定单独HBsAg阳性或HBsAg和HBeAg均阳性的男性与两者均阴性的男性相比发生肝细胞癌的相对风险。
在92359人年的随访期间，有111例新诊断的肝细胞癌病例。HBsAg和HBeAg均阳性的男性中肝细胞癌的发病率为每100000人年1169例，仅HBsAg阳性的男性为每100000人年324例，两者均阴性的男性为每100000人年39例。在调整了年龄、性别、是否存在丙型肝炎病毒抗体、吸烟状况以及是否饮酒后，单独HBsAg阳性的男性发生肝细胞癌的相对风险为9.6（95%置信区间为6.0至15.2），HBsAg和HBeAg均阳性的男性与两者均阴性的男性相比为60.2（95%置信区间为35.5至102.1）。
HBeAg阳性与肝细胞癌风险增加相关。
