Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
Department of Public Health, College of Medicine, Bigdata Research Center, Fu-Jen Catholic University, New Taipei, Taiwan.
Gastroenterology. 2016 Sep;151(3):472-480.e1. doi: 10.1053/j.gastro.2016.05.048. Epub 2016 Jun 4.
BACKGROUND & AIMS: The incidence of hepatocellular carcinoma (HCC) increases with age, but protective antibody responses decrease with time after infants are immunized against hepatitis B virus (HBV). We investigated whether immunization of infants against HBV prevents their developing HCC as adults. We also searched for strategies to maximize the cancer-preventive effects. METHODS: We collected data from 2 Taiwan HCC registry systems on 1509 patients (6-26 years old) diagnosed with HCC from 1983 through 2011. Data on history of HBV immunization and prenatal maternal levels of HBV antigens of all HCC patients born after July 1984 were retrieved from the HBV immunization data bank of the Taiwan Center for Disease Control. We collected data on birth cohort-specific populations (6-26 years old) of Taiwan using the National Household Registry System. Rates of HCC incidence per 10(5) person-years were derived by dividing the number of patients with HCC by the person-years of the general population. Relative risks (RR) for HCC were estimated by Poisson regression analysis in vaccinated vs unvaccinated birth cohorts. We stratified patients by age group to evaluate the association of birth cohorts and HCC risks. RESULTS: Of the 1509 patients with HCC, 1343 were born before, and 166 were born after, the HBV vaccination program began. HCC incidence per 10(5) person-years was 0.92 in the unvaccinated cohort and 0.23 in the vaccinated birth cohorts. The RRs for HCC in patients 6-9 years old, 10-14 years old, 15-19 years old, and 20-26 years old who were vaccinated vs unvaccinated were 0.26 (95% confidence interval [CI], 0.17-0.40), 0.34 (95% CI, 0.25-0.48), 0.37 (95% CI, 0.25-0.51), and 0.42 (95% CI, 0.32-0.56), respectively. The RR for HCC in 6- to 26-year-olds was lower in the later vs the earlier cohorts (born in 1992-2005 vs 1986-1992; P < .001 and 1986-1992 vs 1984-1986; P < .002). Transmission of HBV from highly infectious mothers and incomplete immunization were associated with development of HCC. CONCLUSIONS: Based on an analysis of 1509 patients with HCC in Taiwan, immunization of infants against HBV reduces their risk of developing HCC as children and young adults. Improving HBV vaccination strategies and overcoming risk factors could reduce the incidence of liver cancer.
背景与目的：肝细胞癌（HCC）的发病率随年龄增长而增加，但婴儿接种乙型肝炎病毒（HBV）疫苗后，随着时间的推移，保护性抗体反应会下降。我们研究了婴儿接种 HBV 疫苗是否能预防其成年后患 HCC。我们还寻找了最大限度发挥癌症预防效果的策略。
方法：我们从台湾两个 HCC 登记系统收集了 1509 名（6-26 岁）于 1983 年至 2011 年期间确诊 HCC 的患者的数据。所有于 1984 年 7 月后出生的 HCC 患者的 HBV 免疫史和母亲产前 HBV 抗原水平的数据均从台湾疾病管制中心的 HBV 免疫数据库中获取。我们从国家家庭登记系统收集了台湾特定出生队列人群（6-26 岁）的数据。每 105 人年 HCC 发生率是通过将 HCC 患者人数除以一般人群的人年数得出的。通过泊松回归分析，在接种疫苗与未接种疫苗的出生队列中估算 HCC 的相对风险（RR）。我们按年龄组对患者进行分层，以评估出生队列与 HCC 风险的关系。
结果：在 1509 名 HCC 患者中，1343 名患者出生于 HBV 疫苗接种计划开始之前，166 名患者出生于该计划开始之后。未接种疫苗队列的 HCC 发生率为每 105 人年 0.92，接种疫苗的出生队列为每 105 人年 0.23。6-9 岁、10-14 岁、15-19 岁和 20-26 岁接种疫苗与未接种疫苗的患者 HCC 的 RR 分别为 0.26（95%置信区间[CI]，0.17-0.40）、0.34（95% CI，0.25-0.48）、0.37（95% CI，0.25-0.51）和 0.42（95% CI，0.32-0.56）。与早期队列（1992-2005 年出生与 1986-1992 年出生；P<0.001 和 1986-1992 年出生与 1984-1986 年出生；P<0.002）相比，6-26 岁时 HCC 的 RR 较低。HBV 从高传染性母亲传播和免疫不完全与 HCC 的发生有关。
结论：基于对台湾 1509 名 HCC 患者的分析，婴儿接种 HBV 疫苗可降低其成年后患 HCC 的风险。改进 HBV 疫苗接种策略和克服风险因素可以降低肝癌的发病率。
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