摘要：Objectives. To evaluate the effectiveness of the hepatitis B virus (HBV) vaccination program in Greenland, which targets children born to mothers who are positive for HBV surface antigen (HBsAg), we determined vaccination coverage, levels of postvaccination antibodies, and frequency of breakthrough infections in at-risk children. Methods. We conducted a population-based retrospective cohort study with data from nationwide registries. We identified all children born to HBsAg-positive mothers from 1992 to 2007 and collected data on their HBV vaccination status. In 2008 to 2010, we tested the children for HBV core antibody, HBsAg, and anti-HBsAg antibody (HBsAb). Results. Of 4050 pregnant women, 3.2% were HBsAg positive. Of 207 children born to these women, 20% received no vaccinations, and only 58% received at least 3 vaccinations. At follow-up, HBsAb levels in vaccinated children were much lower than expected, and 8 (6%) of 140 at-risk children had breakthrough infections, with 4 chronically infected (persistently HBsAg positive). Conclusions. The prevention program targeting children at risk for HBV in Greenland is ineffective. HBV vaccination should be included in the universal childhood vaccination program, and postvaccination HBsAb levels should be monitored. Hepatitis B virus (HBV) infection may cause chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. 1 Perinatal mother-to-child transmission is a major cause of chronic HBV infection in endemic areas. However, up to 90% of transmissions can be prevented with immunoglobulin given within 48 hours postpartum in conjunction with 3 or 4 HBV vaccine doses, beginning at birth and completed within 12 months. 2,3 In 1992, the World Health Organization recommended that all countries include HBV vaccination in the universal childhood vaccination program by 1997 4 ; by December 2007, 171 of the world's 193 countries had complied. 5 In the remaining 22 countries, some rely on identifying high-risk groups (e.g., the low-endemic Scandinavian countries); others, mainly sub-Saharan countries where infection is endemic, have no HBV vaccination strategy. 6 Like other Arctic populations, the Inuit in Greenland have a high prevalence of HBV infection. Overall, 40% to 45% of the population have been infected (i.e., they test positive for HBV core antibody [HBcAb]), and 5% to 10% are chronically infected (i.e., they also test positive for HBV surface antigen [HBsAg]). The prevalence of HBsAg has not changed in the past 30 years. 7–9 Reports have indicated that the incidence of cirrhosis and liver cancer is lower in Greenland than in other highly endemic countries and lower even than in Denmark, where HBV infection is not endemic. 7–11 Hence, policymakers have not considered HBV infection to be a major health problem at the population level, and HBV prevention has relied on vaccination of at-risk infants. Since 1992, Greenlandic policy has been to screen all pregnant women for HBsAg and to vaccinate infants of HBsAg-positive mothers. The program recommends that children receive 200 international units intramuscular HBV-specific immunoglobulin (HBIG; Aunativ, Biovitrum AB, Stockholm, Sweden) and 4 doses of 10 micrograms intramuscular recombinant HBV vaccine (EngerixB, SmithKline, Rixensart, Belgium), with HBIG and the first vaccination given within 48 hours after birth and additional vaccinations given at ages 1, 2, and 12 months. Recently, a study reported that 3 siblings of a known chronic carrier of HBV were found to be chronically infected. 12 The same study described horizontal transmission of HBV and hepatitis D among children in Greenland. 12 These observations raised concern that the targeted HBV vaccination program was not fully effective and was insufficient to reduce the burden of HBV-related disease in Greenland. We carried out a retrospective population-based cohort study with data from national registries, with 3 objectives: (1) to determine HBV vaccination coverage in children of HBsAg-positive mothers; (2) to estimate the effectiveness of HBV vaccination, as measured by HBsAg antibody (HBsAb) levels; and (3) to determine the frequency of breakthrough infections in at-risk children.
