Hepatitis B immunity in adolescents and necessity for boost vaccination: 23 years after nationwide hepatitis B virus vaccination program in Taiwan

The first universal hepatitis B vaccination program for newborns in the world was launched in Taiwan in July 1984. Most studies on the effectiveness of hepatitis B vaccination focused on the seroprevalence of HBs Ag among children under 14 years old. Only few studies focused on the seropositivity of anti-HBs among adolescents aged 15–18 years old. The present study aimed to evaluate the impact of the nationwide hepatitis B vaccination program on the immunity to HBV infection and the necessity of boost among adolescents. In this study including eight annual seroprevalence surveys from 2000 to 2007, 2342 college entrants (1589 15-year-olds in group I and 753 18-year-olds in group II) and 1851 university freshmen (18-year-olds in group III) participated. Subjects identified anti-HBs, HBs Ag and anti-HBc negative were given boost three doses of HBV vaccine. The HBs Ag seroprevalence was 11.6%, 3.5% and 1.0% for participants who were born before 1984, 1984–1986 and after 1986. The anti-HBs-seropositive rates were significantly higher in group II (83.1%) than in group I (53.0%) and group III (53.5%). All 572 participants who were seronegative for anti-HBs, HBs Ag and anti-HBc became anti-HBs-seropositive after catch-up vaccination. It is concluded that the anti-HBs-seropositive rate decreased to 50% in 15 years after vaccination, and boost vaccination was 100% effective. The necessity and age for boost among anti-HBs negative adolescents and the timing of the first immunization should be further evaluated.     

Hepatitis B virus infection in northern Uganda: Impact of pentavalent hepatitis B vaccination

Chronic hepatitis B virus infection (CHBI) is effectively prevented by vaccination starting at birth. Beginning in 2002 Uganda adopted a policy of providing the pentavalent hepatitis B vaccine starting at 6 weeks of age. However, there is concern that this delay may leave the infant vulnerable to infection during the first 6 weeks of life. We assessed whether vaccination at 6 weeks was an effective strategy by HBV serologic study. Of 656 persons tested for HBV, 9.4% were chronically infected; among children aged 5–9 years the prevalence was 7.6%. Of all tested, 73 were born (i.e., aged ≤4 years) after the introduction of the pentavalent vaccine; none were infected with HBV (p = 0.003). In this study, vaccination with the pentavalent vaccine at 6 weeks did not result in CHBI, but rather provides an opportunity to prevent mother-to-infant transmission of HBV infection where there is no access to birth-dose vaccine.     

Hepatitis B seroprevalence and anamnestic response amongst Taiwanese young adults with full vaccination in infancy, 20 years subsequent to national hepatitis B vaccination

The long-term protective effect of hepatitis B virus (HB) vaccination against HB infection and the necessity for routine booster vaccination in young-adult age subsequent to full HB immunization at birth remain issues of some debate currently. This study is aimed at evaluating the seroprevalence of HB infection and the response to HB booster vaccination amongst young-adult university students who had previously undergone full vaccination during their infancy. Eight hundred and forty-three subjects (mean age 18.7+/-0.4 years), 492 males and 351 females, with a complete HB vaccination during infancy were enrolled into this study. The prevalence of natural HB infection, chronic HB-carrier status, and HB-na?ve group was, respectively, 4.1%, 1.4%, and 62.3%. Amongst 316 study subjects who were na?ve to HB infection and had received one HB booster at time of university entrance health examination, 49.6%, 91.4%, and 97.5% of the participants with a serum anti-HBs level <0.1, 0.1 to <1.0 and 1.0 to <10.0mIU/mL prior to the booster vaccination, respectively, developed an anamnestic response (i.e., >/=10mIU/mL) to a booster dose of HB vaccine. Full implementation of national-wide HB vaccination program in 1986 has significantly reduced the incidence of HB infection and associated carrier rate in Taiwan. Approximately three-quarter of the subjects who were na?ve to HB infection and had received one HB booster demonstrated an anamnestic response to a booster HB vaccine. The higher the anti-HBs titers remained for an individual subsequent to primary vaccination, the greater the anamnestic response observed. Additional long-term follow-up studies are needed for young adults initially vaccinated for HB in their infancy.     

乙型肝炎疫苗应用20年乙型肝炎病毒感染状况调查分析

目的 了解周口市乙肝疫苗应用20年后乙肝病毒表面抗原携带情况,为完善乙肝预防控制措施提供依据。方法 以周口市1~19岁人群为调查对象,采用酶联免疫吸附试验检测人群中HBsAg携带情况。结果 周口市调查人群HBsAg阳性率2011年(2.30%)与1999年(7.97%)比下降71.14%,<5岁儿童HBsAg流行率<1%。 结论 乙肝疫苗免疫接种效果显著。做好新生儿乙肝疫苗预防接种,加强中学生及成年人的乙肝疫苗免疫接种。     

Probabilistic cost-effectiveness analysis of the long-term effect of universal hepatitis B vaccination: An experience from Taiwan with high hepatitis B virus infection and Hepatitis B e Antigen positive prevalence

Aim

To assess cost-effectiveness of hepatitis B virus (HBV) vaccination strategies from health care payer and societal perspectives, focusing on the long-term effect, in Taiwan where prevalence of HBV and Hepatitis B e Antigen (HBeAg) is high.

Methods

A decision analysis was performed to compare total costs and effectiveness between two vaccination strategies: universal vaccination and no-vaccination. The Markov process was defined as a series of states including acute HBV infection, asymptomatic carrier, chronic hepatitis, compensated and decompensated liver cirrhosis, hepatoma, and death. Direct and indirect costs were also imputed based on estimates. The incremental cost-effectiveness ratio (ICER) per life-year gained and quality-adjusted life years gained were calculated at a 3% discount rate. By assigning a series of specific distributions to each parameter, a probabilistic cost-effective analysis using Monte Carlo simulation was conducted to yield 5000 ICER replicates.

Results

The effectiveness of a universal vaccination program for reducing hepatocellular carcinoma cases and deaths was approximately 86%. The average life years gained per subject as a result of such a universal vaccination was 3.9. The vaccination program dominated over a no-vaccination program (less cost and more effectiveness).

Conclusions

A universal vaccination program against hepatitis B infection is not only effective for reducing long-term sequelae but is also a cost-saving primary preventive strategy, which supports a universal infant immunization in endemic area with high prevalence of HBV and HBeAg.     

上海市黄浦区乙型肝炎疫苗免疫后人群乙型肝炎病毒感染状况及危险因素研究

目的 了解上海市黄浦区血源性乙型肝炎(乙肝)疫苗(Hematogenous Hepatitis B Vaccine,HepB-H)免疫后人群乙肝病毒(Hepatitis B Virus,HBV)感染状况及危险因素.方法 采用横断面调查和血清流行病学调查,对上海市黄浦区13～23岁1 545人进行问卷调查,并采集5ml血标本开展血清流行病学调查,分析HBV感染情况及相关感染危险因素.结果 调查人群HBV感染率为5.60％,且男性高于女性;总体抗-HBs阳性率为39.80％,且女性高于男性.多因素分析结果显示,男性、母亲妊娠时HBsAg阳性、直接接触被家人出血污染的物品是HBV感染的独立危险因素(P＜0.05).结论 乙肝疫苗免后无应答可能是目标人群感染乙肝病毒的原因之一,应定期监测免后人群抗-HBs水平;同时,加强以家庭为单位的乙肝防治健康教育,降低患者家家属因密切接触而感染乙肝病毒的危险性.     

中国乙型肝炎的流行及控制进展

  目的  调查分析深圳市罗湖区2010 — 2020年乙肝携带、新发感染和乙肝相关疾病死亡率流行特征,评估示范区乙肝综合防治效果。  方法  利用多阶段整群随机抽样的方法,分别于2010年和2020年对罗湖区进行乙肝携带率调查,同时收集了示范区罗湖区和对照区龙岗区2010 — 2020年乙肝新发感染、乙肝相关疾病死亡及人口学资料,运用描述性流行病学的方法,分析罗湖区乙肝携带率、新发感染率和相关疾病死亡率的现况和变化趋势。  结果  罗湖区2010年和2020年标化后的乙肝携带率分别为8.74 % 和6.91 %,差异具有统计学意义（P < 0.01）。乙肝新发感染率由2010年的2.88/10万下降至2020年的0.09/10万,下降了96.88 %。乙肝相关疾病的标准化死亡率2010年和2020年分别为5.36/10万和5.67/10万,变化趋势整体呈平稳状态,差异无统计学意义（P = 0.561）。罗湖区与龙岗区横向比较显示,2010 — 2020年罗湖区乙肝新发感染率均低于龙岗区,差异均有统计学意义（P < 0.05）;罗湖区在2010 — 2015年内乙肝相关疾病的标准化死亡率均高于龙岗区,2016 — 2017年两区基本持平,自2018年起,罗湖区低于龙岗区,差异有统计学意义（P < 0.05）。  结论  病毒性肝炎综合防治重大科技专项在深圳市罗湖区经过10年的努力取得显著成效,逐步形成了可推广的乙肝社区综合防治模式。     

广州市青少年学生乙型肝炎病毒感染状况及危险因素调查

目的了解推广使用乙型肝炎疫苗后,广州市青少年学生乙型肝炎病毒感染状况和感染危险因素。方法选取广州市29所中学的初一和高一学生共14744人作为调查对象,检测乙型肝炎表面抗原（HBsAg）和抗体（抗-FiBs）,HBsAg与抗-HBs同时阳性者作乙型肝炎病毒S基因扩增和DNA序列分析。以统一的问卷对HBsAg阳性者进行流行病学调查。结果检出HBsAg阳性者424人,阳性率为2．9％。抗-HBs阳性者12201人,阳性率为82.8％。4人HBsAg、抗-HBs同时阳性,其中1人S基因“a”决定族第126位的异亮氨酸（ATT）变为苏氨酸（ACT）,第143位由丝氨酸（TCG）变为苏氨酸（ACG）,第145位由甘氨酸（GGA）变为精氨酸（AGA）,另外3人未检出S基因“a”决定簇氨基酸变异。流行病学调查提示部分学生问卷可能通过母婴传播以及日常生活密切接触感乙型肝炎病毒。结论乙型肝炎疫苗是预防乙型肝炎的有效制荆。病毒S基因“a”决定簇变异可使乙型肝炎疫苗保护失败,但目前的发生率较低,无须改变疫苗的制备及免疫策略。     

乙型肝炎病毒表面抗原在慢性乙型肝炎病毒感染后不同临床阶段的定量检测及临床意义

目的 测定慢性乙型肝炎病毒（HBV）感染后不同临床阶段患者血清乙型肝炎病毒表面抗原（HBsAg）定量,同时探究其与患者血清HBV DNA水平和年龄的相关性.方法 将未经抗病毒治疗的774例慢性HBV感染患者按照临床特征分为六组：慢性HBV携带组（102例）、非活动性HBsAg携带组（211例）、乙型肝炎病毒e抗原（HBeAg）阳性慢性乙型肝炎组（236例）、HBeAg阴性慢性乙型肝炎组（114例）、HBeAg阳性乙型肝炎肝硬化组（52例）、HBeAg阴性乙型肝炎肝硬化组（59例）,采用化学发光微粒子免疫分析法测定患者血清HBsAg定量,实时荧光定量聚合酶链反应法测定患者血清中HBV DNA定量,血清HBsAg和HBV DNA需要经常用对数转换后进行组间比较.结果 HBsAg定量由高到低分别为慢性HBV携带组、HBeAg阳性慢性乙型肝炎组、HBeAg阴性慢性乙型肝炎组、非活动性HBsAg携带组、HBeAg阴性乙型肝炎肝硬化组和HBeAg阳性乙型肝炎肝硬化组[7.80（6.69 ～ 8.32）、7.11（5.42～8.27）、6.57（5.66 ～ 7.53）、6.38（4.39～ 7.40）、6.22（4.84～ 6.91）、6.13 （5.48～7.01）].HBeAg阳性慢性乙型肝炎组和HBeAg阴性慢性乙型肝炎组HBsAg定量与HBV DNA呈正相关（r=0.714和0.390,P＜0.01）.慢性HBV感染患者血清HBsAg的定量与年龄呈负相关（r=-0.416,P＜0.01）;监测年龄≥40岁非活动性HBsAg携带者的血清HBsAg定量有重要的临床价值.结论 慢性HBV感染后不同临床阶段患者血清HBsAg定量不同,血清HBsAg定量与患者HBV DNA水平和年龄相关,临床上应重点监测年龄≥40岁非活动性HBsAg携带患者血清HBsAg定量.     

启东乙型肝炎干预研究:2013年随访人群HBV感染及慢性肝病现患调查

目的 分析新生儿接种乙型肝炎(乙肝)疫苗人群在达到婚配年龄后罹患慢性乙肝、肝硬化的远期保护作用。方法 2013年1-10月采用横断面调查方法,对启东乙肝干预研究(QHBIS)的研究对象分层随机抽样,并行ALT、HBV感染血清学标志物(HBsAg、HBeAg、抗-HBs、抗-HBc、抗-HBe)检测及肝胆B超检查。计算HBV感染血清学标志物各指标的阳性率,慢性乙肝及肝硬化的患病率,疫苗组及对照组人群按性别分层后, χ²检验比较各组间率的差异。结果 共获得新生儿乙肝疫苗接种组(疫苗组)4 421人和对照组3 880人,平均年龄分别为(25.59±1.84)岁和(26.61±2.24)岁。疫苗组HBsAg、单独抗-HBs、抗-HBc、HBeAg、抗-HBe阳性率分别为2.38%、37.73%、3.78%、0.57%、2.15%,对照组分别为9.02%、29.41%、16.83%、2.73%、8.87%,两组间血清学标志物各指标的差异均有统计学意义(P <0.05)。疫苗组慢性乙肝活动期、肝纤维化及肝硬化患病率分别为0.45%和0.16%,对照组分别为1.29%和0.39%,组间差异均有统计学意义(P <0.05)。按性别分层后,疫苗组男性慢性乙肝活动期患病率高于女性,差异有统计学意义(P <0.05);在对照组,不管是慢性乙肝活动期患病率还是肝纤维化及肝硬化患病率,男性均高于女性,差异有统计学意义(P <0.05)。结论 新生儿接种乙肝疫苗对慢性HBV感染的保护作用可延长至婚配年龄后,而不同性别人群慢性乙肝与肝硬化现患保护作用的差异值得进一步研究。     

Trend in incidence of hepatitis B virus infection during a decade of universal childhood hepatitis B vaccination in Saudi Arabia

Since 1990, the national strategy to eliminate hepatitis B virus (HBV) infection in Saudi Arabia has included universal administration of HBV vaccine to all infants. From 1990 to 1995 this vaccine was also routinely administered to children at school entry. The prevalence of hepatitis B surface antigen (HBsAg) among children before this programme was reported to be 6.7%. The objective of this study was to describe the trend in incidence of HBV infection over a decade of surveillance following the introduction of this programme. From January 1990 to December 1999 a total of 30,784 cases of HBV infection (positive for HBsAg) were reported. The total number of HBV infections among children <15 years of age was 4180 cases, with a prevalence of 0.05%. The total number of HBV infections among adults was 26,604 cases, with a prevalence of 0.22%. The prevalence varied by region, ranging from 0.03% to 0.72% with a mean prevalence of 0.15%. There was a clear decline in incidence among children whereas the incidence in adults slightly rose, perhaps owing to population growth estimated to be 3.3% annually. This study showed that the universal childhood HBV vaccination programme had an enormous positive impact on HBsAg seroprevalence among children in Saudi Arabia.     

Hepatitis B screening in a northern Irish mental handicap institution: relevance to hepatitis B vaccination

The current DHSS guidelines on immunisation against hepatitis B in mental handicap hospitals recommend vaccination for personnel at risk directly involved in patient care (who may have direct contact with patients or their body fluids) and for new admissions into institutions where the incidence is known to be high. We report a serological survey of hepatitis B markers in over 99% of the residents of a large mental handicap hospital. Of 720 patients tested only one carried hepatitis surface antigen. This patient was anti-HBe positive. Only 4.5% of the residents carried any hepatitis marker. These results do not suggest the need for a local vaccination programme for patients or staff.     

Dramatic decline in acute hepatitis B infection and disease incidence rates among adolescents and young people after 12 years of a mass hepatitis B vaccination programme of pre-adolescents in the schools of Catalonia (Spain)

The aim of the study was to describe the impact of hepatitis B vaccination and disease incidence in adolescents and young people 12 years after the launching of a mass hepatitis B vaccination of pre-adolescents in schools. Vaccination coverage was assessed using administrative and serological data. Infection trends were evaluated by means of seroepidemiological surveys. High levels of vaccination coverage and vaccine-induced immunity were achieved. The resulting low proportions of susceptible adolescents and young people have undoubtedly contributed to the substantial reduction in the prevalence of hepatitis B infection in the 15-24 years age group (0.9 per 100 in 2001 versus 9.3 per 100 in 1986) and in the reported incidence of hepatitis B cases (80% reduction). Over the last 3 years, the declining trend seems to have been halted, although 35% of cases reported during this period corresponded to immigrants.     

乙肝疫苗接种是根除乙型肝炎的关键措施

乙型肝炎病毒感染是全球性健康问题,据估计全世界至少有3.6亿慢性乙肝病毒感染者.目前控制乙肝病毒感染最有效的方法是用安全的乙肝疫苗免疫所有易感人群,尤其是年幼儿童.通过疫苗接种、有效的抗病毒治疗及中断传播的联合措施可使乙肝病毒感染得到控制,最终达到根除乙型肝炎的目的 .该文综述了乙肝疫苗的研发过程,阐述了其在乙肝病毒暴露前和暴露后处置中的作用,以及乙肝疫苗接种后保护力持续时间和需要加强剂量等问题.儿童计划免疫接种乙肝疫苗减少了乙肝病毒携带者、急性和慢性感染性疾病(包括肝细胞癌)的发生.同时,该文也讨论了人体清除乙肝病毒和最终根除乙型肝炎的趋向.     

Immunity to hepatitis A and B persists for at least 15 years after immunisation of adolescents with a combined hepatitis A and B vaccine

BackgroundThe exact duration of antibody persistence to hepatitis A and B and the need for booster dosing following primary immunisation remains undefined. A long-term study was designed to follow antibody persistence and immune memory on an annual basis for up to 15 years following vaccination during adolescence.MethodsSubjects received a combined hepatitis A and B vaccine (Twinrix™, GSK Vaccines, Belgium) at 12–15 years of age, either as 2-dose of the adult formulation or 3-dose of the paediatric formulation. Blood samples were taken every year thereafter to assess antibody persistence and immune memory to hepatitis A and B. Antibodies to hepatitis A virus (anti-HAV) and hepatitis B surface antigen (anti-HBs) were measured at Years 11–15. At Year 15 immune memory was further assessed by measuring the anamnestic response to a challenge dose of the monovalent vaccine, which was administered to subjects whose antibody concentrations fell below the pre-defined cut-offs (anti-HAV: <15 mIU/mL; anti-HBs: <10 mIU/mL).Results209 subjects returned for follow-up at Year 15 of whom 162 were included in the long-term according-to-protocol immunogenicity cohort. All subjects remained seropositive for anti-HAV antibodies, while 81.1% and 81.8% still had anti-HBs antibodies ≥10 mIU/mL in the 2- and 3-dose groups, respectively. Following hepatitis B vaccine challenge dose administration to 19 subjects, all except one in the 3-dose group, mounted a robust anamnestic response. The safety and reactogenicity profile of the hepatitis B challenge was consistent with previous experience.ConclusionImmunity to hepatitis A and B persists 15 years after adolescent vaccination with a combined hepatitis A and B vaccine. Highly effective anamnestic response indicates that a booster dose should not be required for 15 years after primary vaccination.Trial registrationhttp://www.clinicaltrials.gov NCT00875485.     

Seroprevalence of hepatitis C virus infection and its association with natural infection of hepatitis B virus among preschool children in Taiwan

Taiwan is a hyperendemic area of hepatitis B virus (HBV) infection where chronic hepatitis B is the most important cause of liver cirrhosis and hepatoma. Since, diagnostic kit for detecting hepatitis C virus (HCV) infection has been developed, HCV was found to be another important etiology of chronic liver disease. In order to study the seroprevalence of HCV infection among preschool children after mass hepatitis B vaccination program in Taiwan, a community-based survey was carried out in 54 kindergartens in 10 urban areas, 10 rural areas, and two aboriginal areas randomly selected through stratified sampling. Serum specimens of 2538 preschool children were screened for the HCV antibodies (anti-HCV) by a commercially available third-generation microparticle enzyme immunoassay and for HBV markers by radioimmunoassay methods. The multivariate-adjusted odd ratios (OR_m) with their 95% confidence intervals (CI) were estimated through the multiple logistic regression analysis. A total of 58 children were anti-HCV seropositive, giving a prevalence of 2.3%. The prevalence of anti-HCV was 1.0% (5 of 484) among aboriginal children, a significantly decreased seroprevalence compared with those among other ethnic groups after multivariate adjustment. Boys had a higher anti-HCV seroprevalence, but not statistically significantly different from girls (OR_m: 1.6; 95% CI: 0.9–2.8; p = 0.08). The seroprevalence of the age group of 3–4 years was lower than that of the age group of 5–6 years (OR_m: 2.2; 95% CI: 1.1–4.2; p = 0.02). After multivariate adjustment, preschool children with natural HBV infection had a higher anti-HCV seroprevalence, but not statistically significantly different from those without natural HBV-infection (OR_m: 2.6; 95% CI: 0.9–7.4; p = 0.08 for HBV-infected vs. uninfected). HCV infection varies with gender, residential area, and natural HBV infection. HCV and HBV might share common transmission routes in Taiwan.