Prevalence of hepatitis B virus infection in a highly endemic area of southern China after catch-up immunization

The Chinese national goals for control of hepatitis B virus (HBV) infection were to achieve a prevalence of HBsAg below 7% for the entire population, and 1% for children under 5-year old, by 2010. To determine whether Guangxi, a multi-minority province with a low socio-economic status and a very high prevalence of HBV, achieved this goal, a seroepidemiological survey of HBV infection was carried out using stratified, random cluster sampling. The results show that the overall prevalence of HBsAg is 9.16% [95% confidence interval (CI) = 8.32-10%]. The prevalence in males (10.96%, 95% CI = 9.64-12.28%) is significantly higher than in females (7.71%, 95% CI = 6.64-8.78%; χ(2) = 10.5923, P < 0.05). The prevalence in children under 5-year old is 3.62% (95% CI = 0.60-6.64%) and increases with age. The prevalence of HBsAg in non-immunized individuals is significantly higher than in those immunized completely, although not within 24 hr of birth (χ(2) = 31.426, P < 0.05); a significant difference was found in those below the age of 20 years but not in older persons. Gender, age, immunization history, and familial HBsAg carriers are risk factors for infection. In conclusion, this study indicates that Guangxi has not reached the goal for the control of HBV infection. Catch-up HBV immunization may not protect adults effectively against infection in highly endemic regions.     

我国乙型肝炎疫苗免疫

自 1 992年起 ,我国建议对婴儿进行国产乙型肝炎疫苗的常规免疫 ,接种程序为 0、1、6月 ,以预防乙型肝炎病毒 (HBV)的围产期传播。为了评价儿童的乙型肝炎疫苗覆盖率 ,1 999年对我国 31个省市自治区 2 5 878名 3岁以下儿童 ,进行了一次全国性调查。城市 1 2月龄以下儿童的乙型肝炎疫苗覆盖率为 88 5 % ,农村为 6 2 7% ;各省市自治区的乙型肝炎疫苗覆盖率不同 ,有 4个省为≥ 90 % ,9个省为 75 %～ 89% ,8个省为 5 0 %～ 74 % ,1 0个省为 <5 0 %。乙型肝炎疫苗覆盖率高与社会经济状况好、对乙型肝炎认识程度高、卫生保健服务完善 (如城市、非山区 )、非少数民族、在医院而不是在家里出生密切相关。我国于 2 0 0 2年将新生儿乙型肝炎疫苗正式纳入计划免疫 ,向所有新生儿免费 (除手续费外 )接种乙型肝炎疫苗 ,中央政府向贫困地区特别是西部 1 2个省提供资助 ,其他省由地方政府提供乙型肝炎疫苗资金。婴儿乙型肝炎疫苗常规免疫不仅可预防HBV急性感染 ,还可降低慢性肝病包括肝癌的发病率和死亡率。为了提高安全接种 ,我国卫生部实施了一项全国性行动计划 ,包括至 2 0 0 5年时所有免疫接种均使用一次性自毁注射器 ,以及安全免疫接种培训等     

Hepatitis B virus and sexual behavior in Rakai, Uganda

HIV and hepatitis B virus (HBV) co-infection poses important public health considerations in resource-limited settings. Demographic data and sera from adult participants of the Rakai Health Sciences Program Cohort in Southwestern Uganda were examined to determine HBV seroprevalence patterns in this area of high HIV endemicity prior to the introduction of anti-retroviral therapy. Commercially available EIAs were used to detect prevalent HBV infection (positive for HBV core antibody [anti-HBc] and/or positive HBV surface antigen [HBsAg]), and chronic infection (positive for HBsAg). Of 438 participants, 181 (41%) had prevalent HBV infection while 21 (5%) were infected chronically. Fourteen percent of participants were infected with HIV. Fifty three percent showed evidence of prevalent HBV infection compared to 40% among participants infected with HIV (P = 0.067). Seven percent of participants infected with HIV were HBsAg positive compared to 4% among participants not infected with HIV (P = 0.403). The prevalence of prevalent HBV infection was 55% in adults aged >50 years old, and 11% in persons under 20 years. In multivariable analysis, older age, HIV status, and serologic syphilis were significantly associated with prevalent HBV infection. Transfusion status and receipt of injections were not significantly associated with HBV infection. Contrary to expectations that HBV exposure in Uganda occurred chiefly during childhood, prevalent HBV infection was found to increase with age and was associated sexually transmitted diseases (HIV and syphilis.) Therefore vaccination against HBV, particularly susceptible adults with HIV or at risk of HIV/STDs should be a priority.     

Hepatitis B surface antigen (HBsAg) subtype-specific antibodies in persons vaccinated against hepatitis B

One hundred sixty-three persons immunised against hepatitis B with a vaccine containing HBsAg either of adw or ayw subtype were examined for antibodies against the a, d, and y determinants of HBsAg. Sera were tested for antibodies against HBsAg adw and HBsAg ayw separately by a solid-phase radioimmunoassay using polystyrene beads coated with HBsAg of either adw or ayw subtype, and the relative amounts of antibodies against the single determinants were calculated. After the third immunisation, all vaccinees had antibodies against the common determinant a. A quantitative evaluation showed that on average about 50% of HBsAg-specific antibodies were directed against the a determinant, and about 50% against d or y, respectively. However, as only anti-a is protective against cross-infection with other HBsAg subtypes, the degree of immunity of a person vaccinated against hepatitis B should be evaluated by the determination of antibodies to a rather than antibodies against total HBsAg.     

乙肝疫苗无（低）应答加大剂量再免疫效果分析

目的探讨乙肝疫苗接种后无（低）应答者加大剂量再免疫的效果,以提高乙肝疫苗预防接种的保护率。方法对近3年已完成标准乙肝疫苗免疫接种程序至少一年、复查乙肝病毒标志物均为阴性的健康人群,随机地接受3种再免疫方案,按常规程序（0、1、6个月）予肌肉注射。A组40例：进口重组乙肝疫苗（安在时）,每次剂量40μg;B组40例：安在时,每次剂量20μg;C组40例：国产重组乙肝疫苗,每次剂量20μg。在首针乙肝疫苗接种前及接种后第1、2、7个月（T1、T2、T7）采血检测抗-HBs。结果T1时,进口40μg组、进口20μg组和国产20μg组复种后应答率分别为45．0％（18／40）、37．5％（15／40）和30．0％（12／40）,3组应答率差异无统计学意义（χ^2=1．920,P=0．383）;T2和T7时,3组复种后应答率分别为67．5％（27／40）、47．5％（19／40）、40．0％（16／40）和77．5％（31／40）、55．0％（22／40）、50．0％（20／40）,进口40μg组应答率高于其余两组（χ^2为4．014～6．545之间,P均〈0．05）。T2和T7时,进口40μg组应答率差异无统计学意义（χ^2=1．003,P=0.317）。各组患者复种后均未出现严重副反应。结论对乙肝疫苗无（低）应答者增加疫苗剂量加强免疫是有效的措施,抗-HBs应答率随疫苗剂量增加而提高。进口40μg组加强2针即可,加强3针未能较加强2针明显提高抗-HBs应答率。     

Hepatitis B vaccine produced in yeast

A gene encoding the 226 amino acid hepatitis B surface antigen (HBsAg), subtype adw, was cloned into a generalized vector for the expression of heterologous genes in Saccharomyces cerevisiae. The 5' end of the genomic HBsAg gene was replaced with a chemically synthesized DNA segment that conserved the amino acid sequence of the protein but utilized DNA sequences that optimize translation initiation in yeast. High-cell-density fermentations of laboratory strains of Saccharomyces cerevisiae have been developed in which HBsAg production increases linearly with respect to cell mass. The HBsAg is present as a lipoprotein particle in cell lysates and has been purified to homogeneity. The evidence presented indicates that the HBsAg particles may be formed during lysis of the yeast cells. The purified HBsAg particles have a morphology similar to that of the 22 nm particles present in the serum of human chronic carriers of hepatitis B. The reactivity of the yeast-derived HBsAg particles with a series of monoclonal antibodies is essentially identical to that of human plasma HBsAg. By this analysis, therefore, the structure of the HBsAg protein is similar in yeast and in human particles. The purified yeast HBsAg particles were formulated with alum adjuvant and subsequently were shown to confer immunity in chimpanzees to challenge with two heterologous serotypes (adr, ayw) of hepatitis B virus.     

Hepatitis in AIDS patients

The individuals with HIV infection are more susceptible to develop coinfections with infectious pathogens such as HCV and HBV. The routes of transmission of these pathogens are the same including sexual contact, injection drug use, or at birth from mother to an infant. The main reason of morbidity and mortality in HIV infected individuals is a liver disease in the context of antiretroviral therapy, and coinfection such as HCV and HBV complicates this condition. Nucleos(t)ide analogues are used for HBV infection management, and treatment of HCV infection is done by PegIFN and ribavirin combination and protease inhibitors. In this review, we focused on hepatitis B and C infections in HIV patients along with their therapies.     

Hepatitis B vaccination in infants of mothers infected with human immunodeficiency virus

A study was conducted to investigate the immunogenicity of a recombinant DNA hepatitis B vaccine in neonates and children of HIV-infected women. Immunization against hepatitis B consisted of three 10 μg doses of the vaccine administered on a 0-, 1- and 6-month schedule. The children were followed up for an average of 11 months. Of the 118 HIV-positive neonates who participated in the study, 95 lost their HIV antibodies during the follow-up period. Most (94.2%) of the latter who completed the study responded to the vaccine. Of the 23 who remained HIV-positive, 17 completed the study and 7 produced hepatitis B antibodies. © 1995 Wiley-Liss, inc.     

Asymptomatic hepatitis B carriers who were vaccinated at birth

The long-term persistence of immunity following universal infant immunization against hepatitis B virus (HBV) and the need for a subsequent booster dose in adolescence remain under debate. With data derived from Long'an County, Guangxi, China, we reported previously that the prevalence of hepatitis B surface antigen (HBsAg) among adults born from 1987 to 1993 increases with age, although these individuals had received a first dose of the vaccine within 24 hours of birth. Here, we sought the source of transmission by comparison of genotypes among their family members using phylogenetic analysis of complete HBV S gene sequences. For comparison, we screened 2199 vaccinated individuals aged 5 to 17 in Cang Wu County and 1592 vaccinated individuals aged 3 to 7 in Ling Shan County in Guangxi for HBsAg carriers and investigate their family members. In total, 50 asymptomatic HBsAg carriers who were vaccinated at birth and 152 family members were analyzed. The results showed that 25% (95% CI: 6.0-44.0) of the HBsAg-positive children had not acquired their HBV infection from their mothers. This phenomenon showed a trend that increases with age. Antibody escape mutations were detected in 22.9% (95% CI: 11.0-34.8) of the isolates. In conclusion, a booster dose may be necessary for adolescence who were vaccinated at birth in highly endemic countries.     

Hepatitis B virus infection among pregnant women in Haiti: A cross-sectional serosurvey

BackgroundHepatitis B vaccine administered shortly after birth is highly effective in preventing mother to child transmission (MTCT) of infection. While hepatitis B vaccine was introduced in Haiti as part of a combined pentavalent vaccine in 2012, a birth dose is not yet included in the immunization schedule.ObjectivesDetermine the seroprevalence of hepatitis B virus (HBV) infection among pregnant women to evaluate the risk of MTCT.Study designWe selected 1364 residual serum specimens collected during a 2012 human immunodeficiency virus (HIV) sentinel serosurvey among pregnant women attending antenatal care clinics. Haiti was stratified into two regions: West, which includes metropolitan Port-au-Prince, and non-West, which includes all other departments. We evaluated the association between demographic and socioeconomic characteristics and HIV infection with HBV infection.ResultsOf 1364 selected specimens, 1307 (96%) were available for testing. A total of 422 specimens (32.7%) tested positive for total anti-HBc (38.2% in West vs. 27% in non-West, p < 0.001), and 33 specimens (2.5%) were HBsAg positive (2.1% in West vs. 3% in non-West, p = 0.4). Of HBsAg positive specimens, 79% had detectable HBV DNA. Women aged 30 and older had more than double the odds of positive total anti-HBc than women aged 15–19 years (p < 0.001). Women with secondary (adjusted odds ratio (aOR) = 0.54; 95% CI: 0.36–0.81) and post-secondary education (aOR = 0.40, 95% CI: 0.19–0.79) had lower odds of total anti-HBc positivity compared with women with no education. HIV-status was not associated with HBV infection.ConclusionsHaiti has an intermediate endemicity of chronic HBV infection with high prevalence of positive HBV DNA among chronically infected women. Introduction of a universal birth dose of hepatitis B vaccine might help prevent perinatal HBV transmission.     

Immune response of patients with congenital coagulation disorders to hepatitis B vaccine: suboptimal response and human immunodeficiency virus infection

Seventy-eight patients with congenital coagulation disorders were treated with hepatitis B vaccine either subcutaneously or intradermally. All the children (eight vaccinated subcutaneously and eight vaccinated intradermally) responded. Seventeen of 19 (90%) anti-HIV-negative adults vaccinated subcutaneously and 14/25 (56%) anti-HIV-negative adults vaccinated intradermally showed an immune response. At 24 months, the anti-HBs level was greater than 10 IU/l in all children vaccinated subcutaneously, 83% of children vaccinated intradermally, 77% of adults vaccinated subcutaneously, and 55% of adults vaccinated intradermally. Eight of 15 (53%) adult patients who were anti-HIV positive were also anti-HBc positive before vaccination and 6/8 (75%) failed to produce an amnestic response to vaccine. Subcutaneous vaccination with regular monitoring of anti-HBs levels and appropriate boosting is recommended.     

Hepatitis B infection in Vietnamese families

The occurrence of hepatitis B infection as measured by sensitive serological tests for HBsAg, HBeAg and hepatitis B-specific antibodies was studied in Vietnamese refugee families. HBsAg was found in 10% of 301 children studied. Totally 74% of all HBsAg-positive children had an HBsAg-positive mother or father and an additional 7% had a positive sibling. The distribution of these cases indicated that the risk of HBs-antigenemia was increased 11-fold for those who had an HBsAg-positive mother compared with all other children. The presence of HBeAg in the HBsAg-positive parents was associated with a threefold higher risk of HBs-antigenemia in children as compared with the presence of anti-HBe. It was thus documented that HBV in this population is spread primarily by intrafamilial routes and prophylactic measures within risk families should largely be able to control the appearance of new HBsAg carriers.     

Seroprevalence of hepatitis B virus infection in children in Taipei, 1989: five years after a mass hepatitis B vaccination program

A nationwide hepatitis B vaccination program was launched in Taiwan in 1984. To study the impact of this ongoing program on hepatitis B virus (HBV) infection, a follow-up seroepidemiologic study was carried out in 1989 in a Taipei district where pre-vaccination seroepidemiology had been studied. HBV markers were studied in 1134 apparently healthy children (619 boys and 515 girls) under 13 years of age between March and July 1989. The prevalence of hepatitis B surface antigen (HBsAg) in children under 5 years of age decreased from 9.3% in 1984 to approximately 2% in 1989. A significant decrease in HBsAg prevalence and hepatitis B core antibody in 5- to 8-year-old children who were not immunized against HBV showed that horizontal infection among the older children had also decreased. Thus, this program not only protected vaccinated subjects; the reduction in numbers of highly infectious young HBV carriers also contributed to a lower prevalence of hepatitis B infection and carrier rates in some older children. This study demonstrates that hepatitis B vaccination is effective in protecting the majority of children in hyperendemic areas from HBV infection and from becoming chronic carriers.     

Correlation between two chemiluminescence based assays for quantification of hepatitis B surface antigen in patients with chronic hepatitis B infection

Purpose: Hepatitis B surface Antigen (HBsAg) is the hallmark in diagnosing hepatitis B virus (HBV) infection. In India many commercial assays are available for detection of HBsAg but very few can measure it quantitatively. The present study presents the comparative evaluation of two methods and their correlation with serum HBsAg in chronic hepatitis B (CHB) patients. Materials and Methods: Consecutive patients of CHB were included and there HBsAg levels were measured by two methods: (i) Elecsys, Roche Diagnostics, a qualitative assay and (ii) Architect, Abbott Diagnostics, a quantitative assay. The HBV DNA was measured by real-time polymerase chain reaction (qPCR). Results: Total of 136 patients were included in the study and there was a significant overall correlation between both the assays (correlation coefficient [r] = 0.83; P < 0.001). Assays correlated well with each other across all subgroups of CHB: treatment naïve (r = 0.73; P < 0.001, n = 32), on treatment (r = 0.56; P < 0.05, n = 104), hepatitis Be (HBe) antigen positive (r = 0.67; P < 0.001, n = 62) and anti-HBe positive (r = 0.61; P < 0.05, n = 74) group. On correlation with serum HBV DNA, Architect assay demonstrated good correlation (r = 0.73; P < 0.001, n = 136) as compared to the Elecsys assay (r = 0.27; P = 0.068, n = 136). Architect HBsAg QT assay (A1) also correlated well with HBV DNA in the treatment naïve group (r = 0.69; P < 0.001, n = 32). Conclusions: Our study hence proved that both the assays are comparable and a simple qualitative assay with in-house modification can be used easily for quatitation of HBsAg in clinical samples.     

Hepatitis b virus infection in homes for the aged

A seroepidemiological study was carried out in three different institutions for the aged. Serological evidence of HBV infection and the HBsAg carrier rate were found to be significantly increased in all three institutions with respect to the control group (noninstitutionalized aged). Of the 24 HBsAg asymptomatic chronic carriers 62% were positive for HBeAg. Among 15 patients with acute viral hepatitis, none had a severe course and in three HBsAg was not cleared 4–18 months after transaminase levels became normal. During 12–18 months of follow-up, two asymptomatic seroconversions to HBsAg were observed. Although no single HBV transmission route was identified, the close cohabitation with this high number of HBsAg/HBeAg-positive asymptomatic subjects could lead to an increased risk of spread of HBV within such institutions. Failure to clear HBsAg and the mild, often subclinical, HBV infection observed in these subjects, may be due to immunological abnormalities present in the elderly.     

HBsAg定量与HBV-DNA联合检测在慢性乙型肝炎中的临床意义

目的 探讨慢性乙型肝炎病毒(HBV)感染患者表面抗原定量检测与HBV-DNA相关性,并探讨其检测临床意义.方法 检测2010年12月至2012年12月200例未接受抗病毒治疗及免疫调节剂治疗的慢性HBV感染患者治疗前、治疗中HBsAg与HBV-DNA水平,并随访20例治疗后HBV-DNA转阴患者HBsAg与HBV-DNA水平变化,探究HBsAg定量检测临床意义.结果 慢性乙型肝炎患者未接受抗病毒治疗及免疫调节剂治疗前HBeAg(+)患者HBsAg与HBV-DNA水平显著正相关(r =0.683,P＜0.05),HBeAg(-)患者两者正相关性,但相关性较低(r=0.273,P＜0.05).治疗过程中HBsAg与HBV-DNA水平呈正相关(r=0.41,P＜0.01),65.5％ (131/200)的变化规律为HBsAg随HBV-DNA含量的下降而下降.20例HBV-DNA治疗后转阴(HBV-DNA＜500拷贝/mL)患者,其中6例治疗期间HBsAg定量持续下降,HBsAg定量均＜ 250IU/mL,停药后24周复检HBV-DNA仍为阴性.14例治疗后乙肝病毒定量转阴患者(HBV-DNA＜ 500拷贝/mL),治疗期间HBsAg定量不降或上升,停药后24周复检病毒定量有4例(4/14)出现反弹(HBV-DNA＞ 500拷贝/mL).结论 血清HBsAg含量与HBV-DNA具有相关性,临床可将HBsAg含量与HBV-DNA联合检测,用于慢性HBV感染患者的病情程度预判,监测临床治疗疗效.     

广州市应用乙型肝炎疫苗免疫22年人群血清学效果研究

目的评价广州市长期应用乙型肝炎疫苗（hepatitis B vaccine,HepB）对乙型肝炎（乙肝）免疫防病效果。方法在广州市全市12个区、县级市按照多阶段分层整群抽样法,以家庭为单位对1～59岁人群进行横断面调查分析,包括检测HBsAg、抗-HBs,对HepB接种史及主要乙肝感染危险因素进行问卷调查,评估人群HepB接种率,分析和比较不同年龄组、不同家庭感染状况下接种与未接种HepB人群乙型肝炎病毒感染指标,评价HepB免疫防病效果。结果 1～16岁年龄组乙肝疫苗全程接种率为88.11%（2535/2877）,17～59岁人群有乙肝疫苗免疫史为20.75%（470/2113）。在推行新生儿HepB接种纳入计划免疫管理后出生的1～16岁人群,HBsAg阳性率为1.29%,而出生时尚未开展HepB接种的20～59岁人群HBsAg阳性率为13.72%。1～16岁人群中有HepB接种史人群HBsAg阳性率0.99%,无接种史人群为5.56%,疫苗保护率为82.19%。20～59岁人群接种HepB,基本都不是在新生儿时期,疫苗保护率为52.01%。新生儿接种HepB,母婴乙肝传播阻断率为94.16%,并能有效阻断家庭内水平传播。结论长期实施新生儿接种HepB能控制、消除受种人群乙肝病毒感染,非新生儿人群接种HepB也能显著降低乙肝病毒感染率。