实施乙型肝炎疫苗免疫20年后中国东南部海岛地区乙肝血清和分子流行病学研究
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摘要
本课题共分为两个部分：
第一部分海岛地区乙型病毒性肝炎血清流行病学研究
目的：
通过乙型病毒性肝炎血清流行病学调查,了解乙型肝炎疫苗免疫计划实施20年后,浙江省海岛全年龄层人群乙型肝炎病毒(HBV)的流行现状和影响因素,对海岛地区的乙肝防治效果进行评价。本研究为免疫时代海岛乙肝血清流行病学最新调查结果,对于评价乙肝防治特别是疫苗接种效果,及时调整乙肝免疫和控制策略,有效指导浙江省乙肝防治“十二五”规划目标均具有十分重要的理论和实践意义。
方法：
(1)抽样方法：采用多阶段分层随机整群抽样的方法,将浙江省舟山和玉环两个海岛上的常住居民作为研究总体。首先,根据经济水平,将每个地区所有乡镇/街道分为高、中、低三层。每层随机抽取1个乡镇/街道,其次,在每个乡镇/街道按照经济水平,随机抽取3个自然村/社区。共抽取6个乡镇/街道,18个自然村/社区,共调查15878人。
(2)调查方法：对每个调查对象按统一调查表进行询问调查,同时采集静脉血,分离血清,低温保存,检测相关指标。
(3)检测方法：用酶联免疫法(ELISA)检测乙肝病毒表面抗原(HBsAg)、乙肝病毒表面抗体(Anti-HBs)和乙肝病毒核心抗体(Anti-HBc)。检测在杭州艾迪康生物检测有限公司进行。使用艾康生物技术(杭州)有限公司的ELISA试剂,检测仪器为日本BIO-RAD公司生产的680型酶标分析仪。同时采用IFCC速率法,对每个对象进行丙氨酸氨基转移酶(ALT)检测,采用美国贝克曼CX7全自动生化分析仪,试剂盒购于北京利德曼生化股份有限公司。对表面抗原阳性的≥30岁的人群以社区为单位进行肝癌的初步筛选,甲胎蛋白(AFP)检测采用ELISA法,试剂盒购自郑州博赛生物技术股份有限公司,若AFP阳性的患者再行肝脏B超检查,肝脏彩超检查由各个社区卫生服务中心放射科的医生进行。
(4)统计方法：应用WHO推荐的资料统计软件SPSS13.0进行统计分析。统计方法采用卡方检验,检验水准为双侧α=0.05。p<0.01被认为具有显著性差异。
结果：
在玉环和舟山两个海岛地区14997个有效常住被检样本中,共有1763个样本被检测出HBsAg阳性,标化后阳性率为10.4%；总体的Anti-HBc阳性率标化后为33.1%。调查人群男性HBsAg阳性率、Anti-HBs、Anti-HBc阳性率分别为13.51%、56.9%、39.3%。调查人群女性HBsAg阳性率、Anti-HBs阳性率、Anti-HBc阳性率分别为10.6%、57.0%、40.2%。ALT阳性率为8.2%,其中男、女阳性率分别为12.0%,5.8%。年龄大于30岁并且HBsAg阳性者中,ALT阳性率为0.6%。海岛地区之间,海岛地区与其他地区之间的乙肝流行率均存在显著性差异。
结论：
对比1979年,1992年和2006年开展的全国范围的三次病毒性肝炎血清流行病学调查,我国海岛地区的HBsAg携带率呈逐年下降的趋势,但是下降速度远不及内陆其他地区。我们的研究显示,浙江省海岛地区目前仍为HBV高流行地区。实施乙型肝炎疫苗免疫20年来,海岛地区儿童HBV流行强度显著低于青年人和成人,且人群Anti-HBs流行率已达到较高水平,但是不同地区、不同海岛间,不同性别仍存在显著差异。我们的研究还发现,海岛地区肝癌潜在发生率相对较高。政府应该更加关注海岛上活跃的流动人口,并采取扩大免疫人群等防治措施来控制乙肝流行。
第二部分乙肝感染者的血清分子流行病学研究与相关性分析
目的
通过乙型病毒性肝炎血清流行病学调查,了解乙型肝炎疫苗免疫计划实施20年后,浙江省乙肝感染者的血清学标志物流行情况,并对海岛地区筛查出的乙肝感染者对照平原地区的乙肝感染者做进一步的分层研究(进一步检测乙肝三系定量,HBV-DNA, ALT, AFP, B超),了解不同地域背景下e抗原流行现状和影响因素,并开展血清学标志物与HBV-DNA和ALT之间的相关性研究。以取得最新的数据指导该群体的治疗和预后研究。
方法
(1)抽样方法：
采用多阶段分层随机整群抽样的方法。首先,根据浙江省的两大主要地貌(平原和海岛)选择绍兴县和玉环县,每个地区根据经济水平,将所有乡镇/街道分为高、中、低三层。每层随机抽取1个乡镇.街道,其次,在每个乡镇/街道再根据经济水平,随机抽取3个自然村/社区。共抽取6个乡镇/街道,18个自然村/社区,我们对这18个社区的居民开展乙肝HBsAg检测,筛查出的HBsAg阳性的乙肝感染者作为我们的实验人群,共获有效调查对象8439人。
(2)调查方法：
问卷调查采用集中与入户相结合的调查方法,由经专业培训的调查员按照统一调查问卷,对每个参与者进行面对面的调查,同时采集静脉血,分离血清,低温保存,送检相关指标。
(3)检测方法：
采用荧光定量PCR法,实时、动态监测HBV-DNA载量。检测在通过卫生部PCR实验室认证的基因诊断实验室中进行,使用国产杭州博日科技有限公司提供的FO-33A型PCR扩增仪,试剂购自艾康生物技术(杭州)有限公司。同时,用酶联免疫吸附法(ELISA)测定血清学标志物,选用杭州艾康生物科技公司生产的酶联免疫吸附试验试剂盒。操作严格按照试剂盒说明书,用酶标仪(MULTISKAN MK3)读取和记录结果。此外,采用美国贝克曼CX7全自动生化分析仪检测ALT,试剂盒购于北京利德曼生化股份有限公司,操作按试剂盒提供的标准来判断结果。
(4)统计方法：
采用EpiData3.1软件建立调查数据库,严格按照双录入的要求统一录入,应用WHO推荐的资料统计软件SPSS13.0进行统计分析。统计方法采用卡方检验,检验水准为双侧α=0.05。p<0.01被认为具有显著性差异。
结果
调查对象为HBsAg阳性的感染者,40-49岁的人群的比例达到最高,为33.2%；乙肝感染者HBeAg阳性率为18.5%,其中<20岁和>70岁人群HBeAg阳性率分别为60%和9.2%；男、女性HBeAg阳性率分别为21.9%、14.7%,两者有显著性差异；玉环、绍兴地区的HBeAg阳性率分别为为21.9%、12.9%,两者有显著性差异；HBeAg阳性的人中HBV-DNA阳性率为91.0%,HBeAg阴性的人中HBV-DNA阳性率为45.4%,有显著性差异；在HBV-DNA小于103,103～105,105～107,大于107的人群中HBeAg阳性率分别为3.6%,6.0%,41.1%,94.0%,不同水平的HBV-DNA的人群中HBeAg阳性率有很大的差异；对HBV-DNA和HBeAg定量进行Spearman秩相关分析,发现二者有一定的线性关系(p<0.01),但是相关性较弱(r=0.394<0.4),对HBeAg阳性患者的HBV-DNA和HBeAg定量进行Spearman秩相关分析,发现二者有一定的线性关系(p<0.01),并且正相关性强(r=0.777>0.7); HBV-DNA阳性率在HBeAg阳性并且ALT升高的人群中为95.4%,在HBeAg阳性但ALT正常的人群中为86.4%,两组间有显著的差异(p<0.01)。HBV-DNA阳性率在HBeAg阴性并且ALT升高的人群中为59.6%,在HBeAg阴性但ALT正常的人群中为41.5%,两组间也有显著的差异(p<0.01)。
结论
与1992年浙江省病毒性肝炎流行病学调查结果相比,海岛地区的乙肝感染者高发人群的年龄已从1992年报道的0-9岁和30-39岁推迟到40-49岁,乙肝e抗原在感染者中的流行率与年龄、性别、地域均有重要关系,研究显示HBV-DNA和HBeAg定量呈一定的线性关系,在HBeAg阳性患者中两者的关系尤其明显。HBeAg、HBV-DNA及ALT三者联合有助于综合评价病毒复制及机体反应情况。在没有条件使用PCR方法进行HBV-DNA定量检测的情况下,结合HBeAg和ALT的水平不失为判断HBV活动性及传染性严重程度的先行指标。
This study was divided into two parts.
Part A:Hepatitis B seroepidemiologic investigation in island regions
Objective
We expect to learn about the epidemic situation of HBV among all-aged population in the island regions in Zhejiang Province through this seroepidemiologic investigation. Meanwhile we can learn how the expanded program immunization (EPI) carried out in1992affected the epidemic situation of HBV in this region. Furthermore, we compare our result with epidemic situation in plain region in HBV-DNA, hepatic function, AFP, B ultrasound. We learn the epidemic situation of HBeAg in different regions and the relevance between serum marks, HBV-DNA and ALT. This research has vital theoretical and practical significance in evaluating the effects of prophylaxis and vaccination, adjusting of the HBV immunization strategy in time, guiding the government work in the12th Five-Year Plan in Zhejiang province.
Methods
Stratified clustered-random sampling in different stages was employed in this study. A total of14997residents all-aged were surveyed and blood tested. HBsAg, antibody of HBsAb, and anti body of HBcAb were detected with ELLSA method. ALT and AFP was tested in all the participants and those who were HBsAg positive.
Results
In14997residents surveyed, we find1763residents are HBsAg positive, the adjusted positive rate is10.4%. The adjusted HBcAb positive rate is33.1%.
The adjusted positive rate of HBsAg, HBsAb, HBcAb of male is13.51%、56.9%、39.3%. The adjusted positive rate of HBsAg, HBsAb, HBcAb of female is10.6%、57.0%.40.2%. The rate of elevated ALT is8.2%(12.0%in male,5.8%in female). The rate of elevated ALT among the group over30years old with HBsAg positive is0.6%. The epidemic situation between different islands has significant diversity.
Conclusion
According to three national Viral hepatitis serum epidemiological investigations in1979,1992and2006separately, Chinese Hepatitis B surface antigen(HbsAg) carrier has a downward trend with years. Comparing to the result of the investigation in2006, the hepatitis B prevalence of Zhejiang province also has a obvious decline. The hepatitis B prevalence of island areas (Zhoushan and Yuhuan), however, is still beyond average of Zhejiang province. For purpose of droping national hepatitis B prevalence to low level, the government should give vaccination to more people, put more money down on the vaccination, especially to people whose age are above20and have negative result of HBV markers, as well as high risk group who haven't already vaccinated since1992. What's more, comparing to plain region of China, the government ought to focus more on Hepatitis b transmission condition on active floating population in island regions.
Part B:Hepatitis B seroepidemiological survey and stratification analysis
Object:
The hepatitis B vaccine immunization program has been carried out for20years. To understand the prevalence of serological markers among hepatitis B infections in Zhejiang Province, we made a Hepatitis B seroepidemiological survey and further did stratification analysis among the screened hepatitis B infections in insular areas, controlled them to those in plain areas (further detect hepatitis B three-line quantitative HBV-DNA, liver function, alpha-fetoprotein of AFP, B super). Our aim is to understand the epidemic status and the influencing factors of e antigen between different geographical backgrounds and the correlation between serological markers and HBV-DNA and ALT, which is in order to get the latest data to guide the treatment and prognosis of the groups.
Method:
(1) Stratified clustered-random sampling in different stages were adopted in this study. First, in Shaoxing County and Yuhuan County, which are on behalf of the two major landforms (plains and islands) in Zhejiang Province, we divided all township/street into three layers of high, medium and low, based on the economic level. Select one township/street in each layer randomly. Secondly, select three villages/communities randomly again in every town/street, based on the economic level. In totally, six townships/streets were taken, in which18villages/communities were selected. A total of8439effective objects were surveyed.
(2) The questionnaire survey used the unified questionnaire by the method combined concentrated and households, carried out by the professional investigators face-to-face. Serum samples of each participant were collected at the same time, separated. Then send to test related indicators in cryopreservation.
(3) Using fluorescence quantitative PCR, real-timely, dynamicly monitor the HBV-DNA load in gene diagnostic laboratory which is certificated by the Ministry of Health. The machine is the FO-33A PCR instrument offered by Hangzhou Bo Japan Science and Technology Co., Ltd. and reagents were purchased from ACON Biotech (Hangzhou) Co., Ltd.. Meanwhile, serological markers were measured by enzyme-linked immunosorbent assay (ELISA). The enzyme-linked immunosorbent assay kits were produced by Hangzhou aicon Biotechnology Company. Operation was in strict accordance with the kit instructions and the results were read and record by the microplate reader (MULTISKAN MK3). In addition, select the Beckman CX7automatic biochemical analyzer to test ALT, which was purchased from Beijing Leadman Biochemistry Co., Ltd..The results were judged by standards of the kit.
(4) Adopt the EpiData3.1software to create a survey database and the data was entered in strict accordance with the requirements of the double-entry. Use the statistical software SPSS13.0recommended by WHO to conduct statistic. Statistical methods using the chi-square test and inspection standards for bilateral a=0.05.P<0.01was considered significant difference.
Result:
Respondents were HBsAg positive, in which the proportion of40-49year-old crowd was the highest, at33.2%; HBeAg positive rate was18.5%, of which, the population that less than20years old and older than70-year-old crowd, their positive rates were60%and9.2%each. The HBeAg positive rates of men and women were21.9%and14.7%each. Data was significantly different. In Yuhuan and Shaoxing, HBeAg positive rates were21.9%,12.9%. Both have significant difference. HBV-DNA positive rate was91.0%among HBeAg-positive people and was45.4%among HBeAg negative people, which was significantly different. The HBeAg positive rates in population, which HBV-DNA amounts were less than103,103～105,105～107,>107were3.6%,6.0%,41.1%,94.0%. There were a lot of differences of HBeAg positive rates in the populations of the different levels of hepatitis B viral load. Do the Spearman rank correlation analysis with the HBV-DNA and HBeAg and find linear relationship (p <0.01) between the two, but weak correlation (r=0.394<0.4). Do Spearman rank correlation analysis with HBV-DNA and HBeAg among HBeAg-positive patients, find the linear relationship (p<0.01), and it is a strong correlation (r=0.777>0.7). In the population of HBeAg positive, the ALT elevating and the ALT normal people, their HBV-DNA positive rates were95.4%、86.4%respectively, which was significantly different; in the population of HBeAg negative, the ALT elevating and the ALT normal people, their HBV-DNA positive rates were59.6%、41.5%, which was significantly different.
Conclusion:
Compared with the results of investigation made in1992of Zhejiang province, the age structure of the hepatitis B has largely back goes on to40-49, which prompted the Government that it is important to strengthen the coverage of health examination, which includes the HBV detection, and penetration of health education for the40-49's rural population, in order to detect and treat disease early. Although studies have shown that there is linear relationship between the HBV-DNA and HBeAg, in the clinical, doctors need to consider HBV-DNA and HBeAg amount integratedly, especially the people which HBeAg negative but the HBV-DNA level high. Combining the HBeAg, HBV-DNA and ALT could make comprehensive evaluation of viral replication and the reactions of the body. In no condition to using the PCR method for the quantitative detection of HBV-DNA, HBeAg and ALT levels could be regarded as leading indicators to judge the severity of HBV activity and infectious.
第一部分海岛地区乙型病毒性肝炎血清流行病学研究
目的：
通过乙型病毒性肝炎血清流行病学调查,了解乙型肝炎疫苗免疫计划实施20年后,浙江省海岛全年龄层人群乙型肝炎病毒(HBV)的流行现状和影响因素,对海岛地区的乙肝防治效果进行评价。本研究为免疫时代海岛乙肝血清流行病学最新调查结果,对于评价乙肝防治特别是疫苗接种效果,及时调整乙肝免疫和控制策略,有效指导浙江省乙肝防治“十二五”规划目标均具有十分重要的理论和实践意义。
方法：
(1)抽样方法：采用多阶段分层随机整群抽样的方法,将浙江省舟山和玉环两个海岛上的常住居民作为研究总体。首先,根据经济水平,将每个地区所有乡镇/街道分为高、中、低三层。每层随机抽取1个乡镇/街道,其次,在每个乡镇/街道按照经济水平,随机抽取3个自然村/社区。共抽取6个乡镇/街道,18个自然村/社区,共调查15878人。
(2)调查方法：对每个调查对象按统一调查表进行询问调查,同时采集静脉血,分离血清,低温保存,检测相关指标。
(3)检测方法：用酶联免疫法(ELISA)检测乙肝病毒表面抗原(HBsAg)、乙肝病毒表面抗体(Anti-HBs)和乙肝病毒核心抗体(Anti-HBc)。检测在杭州艾迪康生物检测有限公司进行。使用艾康生物技术(杭州)有限公司的ELISA试剂,检测仪器为日本BIO-RAD公司生产的680型酶标分析仪。同时采用IFCC速率法,对每个对象进行丙氨酸氨基转移酶(ALT)检测,采用美国贝克曼CX7全自动生化分析仪,试剂盒购于北京利德曼生化股份有限公司。对表面抗原阳性的≥30岁的人群以社区为单位进行肝癌的初步筛选,甲胎蛋白(AFP)检测采用ELISA法,试剂盒购自郑州博赛生物技术股份有限公司,若AFP阳性的患者再行肝脏B超检查,肝脏彩超检查由各个社区卫生服务中心放射科的医生进行。
(4)统计方法：应用WHO推荐的资料统计软件SPSS13.0进行统计分析。统计方法采用卡方检验,检验水准为双侧α=0.05。p<0.01被认为具有显著性差异。
结果：
在玉环和舟山两个海岛地区14997个有效常住被检样本中,共有1763个样本被检测出HBsAg阳性,标化后阳性率为10.4%；总体的Anti-HBc阳性率标化后为33.1%。调查人群男性HBsAg阳性率、Anti-HBs、Anti-HBc阳性率分别为13.51%、56.9%、39.3%。调查人群女性HBsAg阳性率、Anti-HBs阳性率、Anti-HBc阳性率分别为10.6%、57.0%、40.2%。ALT阳性率为8.2%,其中男、女阳性率分别为12.0%,5.8%。年龄大于30岁并且HBsAg阳性者中,ALT阳性率为0.6%。海岛地区之间,海岛地区与其他地区之间的乙肝流行率均存在显著性差异。
结论：
对比1979年,1992年和2006年开展的全国范围的三次病毒性肝炎血清流行病学调查,我国海岛地区的HBsAg携带率呈逐年下降的趋势,但是下降速度远不及内陆其他地区。我们的研究显示,浙江省海岛地区目前仍为HBV高流行地区。实施乙型肝炎疫苗免疫20年来,海岛地区儿童HBV流行强度显著低于青年人和成人,且人群Anti-HBs流行率已达到较高水平,但是不同地区、不同海岛间,不同性别仍存在显著差异。我们的研究还发现,海岛地区肝癌潜在发生率相对较高。政府应该更加关注海岛上活跃的流动人口,并采取扩大免疫人群等防治措施来控制乙肝流行。
第二部分乙肝感染者的血清分子流行病学研究与相关性分析
目的
通过乙型病毒性肝炎血清流行病学调查,了解乙型肝炎疫苗免疫计划实施20年后,浙江省乙肝感染者的血清学标志物流行情况,并对海岛地区筛查出的乙肝感染者对照平原地区的乙肝感染者做进一步的分层研究(进一步检测乙肝三系定量,HBV-DNA, ALT, AFP, B超),了解不同地域背景下e抗原流行现状和影响因素,并开展血清学标志物与HBV-DNA和ALT之间的相关性研究。以取得最新的数据指导该群体的治疗和预后研究。
方法
(1)抽样方法：
采用多阶段分层随机整群抽样的方法。首先,根据浙江省的两大主要地貌(平原和海岛)选择绍兴县和玉环县,每个地区根据经济水平,将所有乡镇/街道分为高、中、低三层。每层随机抽取1个乡镇.街道,其次,在每个乡镇/街道再根据经济水平,随机抽取3个自然村/社区。共抽取6个乡镇/街道,18个自然村/社区,我们对这18个社区的居民开展乙肝HBsAg检测,筛查出的HBsAg阳性的乙肝感染者作为我们的实验人群,共获有效调查对象8439人。
(2)调查方法：
问卷调查采用集中与入户相结合的调查方法,由经专业培训的调查员按照统一调查问卷,对每个参与者进行面对面的调查,同时采集静脉血,分离血清,低温保存,送检相关指标。
(3)检测方法：
采用荧光定量PCR法,实时、动态监测HBV-DNA载量。检测在通过卫生部PCR实验室认证的基因诊断实验室中进行,使用国产杭州博日科技有限公司提供的FO-33A型PCR扩增仪,试剂购自艾康生物技术(杭州)有限公司。同时,用酶联免疫吸附法(ELISA)测定血清学标志物,选用杭州艾康生物科技公司生产的酶联免疫吸附试验试剂盒。操作严格按照试剂盒说明书,用酶标仪(MULTISKAN MK3)读取和记录结果。此外,采用美国贝克曼CX7全自动生化分析仪检测ALT,试剂盒购于北京利德曼生化股份有限公司,操作按试剂盒提供的标准来判断结果。
(4)统计方法：
采用EpiData3.1软件建立调查数据库,严格按照双录入的要求统一录入,应用WHO推荐的资料统计软件SPSS13.0进行统计分析。统计方法采用卡方检验,检验水准为双侧α=0.05。p<0.01被认为具有显著性差异。
结果
调查对象为HBsAg阳性的感染者,40-49岁的人群的比例达到最高,为33.2%；乙肝感染者HBeAg阳性率为18.5%,其中<20岁和>70岁人群HBeAg阳性率分别为60%和9.2%；男、女性HBeAg阳性率分别为21.9%、14.7%,两者有显著性差异；玉环、绍兴地区的HBeAg阳性率分别为为21.9%、12.9%,两者有显著性差异；HBeAg阳性的人中HBV-DNA阳性率为91.0%,HBeAg阴性的人中HBV-DNA阳性率为45.4%,有显著性差异；在HBV-DNA小于103,103～105,105～107,大于107的人群中HBeAg阳性率分别为3.6%,6.0%,41.1%,94.0%,不同水平的HBV-DNA的人群中HBeAg阳性率有很大的差异；对HBV-DNA和HBeAg定量进行Spearman秩相关分析,发现二者有一定的线性关系(p<0.01),但是相关性较弱(r=0.394<0.4),对HBeAg阳性患者的HBV-DNA和HBeAg定量进行Spearman秩相关分析,发现二者有一定的线性关系(p<0.01),并且正相关性强(r=0.777>0.7); HBV-DNA阳性率在HBeAg阳性并且ALT升高的人群中为95.4%,在HBeAg阳性但ALT正常的人群中为86.4%,两组间有显著的差异(p<0.01)。HBV-DNA阳性率在HBeAg阴性并且ALT升高的人群中为59.6%,在HBeAg阴性但ALT正常的人群中为41.5%,两组间也有显著的差异(p<0.01)。
结论
与1992年浙江省病毒性肝炎流行病学调查结果相比,海岛地区的乙肝感染者高发人群的年龄已从1992年报道的0-9岁和30-39岁推迟到40-49岁,乙肝e抗原在感染者中的流行率与年龄、性别、地域均有重要关系,研究显示HBV-DNA和HBeAg定量呈一定的线性关系,在HBeAg阳性患者中两者的关系尤其明显。HBeAg、HBV-DNA及ALT三者联合有助于综合评价病毒复制及机体反应情况。在没有条件使用PCR方法进行HBV-DNA定量检测的情况下,结合HBeAg和ALT的水平不失为判断HBV活动性及传染性严重程度的先行指标。
This study was divided into two parts.
Part A:Hepatitis B seroepidemiologic investigation in island regions
Objective
We expect to learn about the epidemic situation of HBV among all-aged population in the island regions in Zhejiang Province through this seroepidemiologic investigation. Meanwhile we can learn how the expanded program immunization (EPI) carried out in1992affected the epidemic situation of HBV in this region. Furthermore, we compare our result with epidemic situation in plain region in HBV-DNA, hepatic function, AFP, B ultrasound. We learn the epidemic situation of HBeAg in different regions and the relevance between serum marks, HBV-DNA and ALT. This research has vital theoretical and practical significance in evaluating the effects of prophylaxis and vaccination, adjusting of the HBV immunization strategy in time, guiding the government work in the12th Five-Year Plan in Zhejiang province.
Methods
Stratified clustered-random sampling in different stages was employed in this study. A total of14997residents all-aged were surveyed and blood tested. HBsAg, antibody of HBsAb, and anti body of HBcAb were detected with ELLSA method. ALT and AFP was tested in all the participants and those who were HBsAg positive.
Results
In14997residents surveyed, we find1763residents are HBsAg positive, the adjusted positive rate is10.4%. The adjusted HBcAb positive rate is33.1%.
The adjusted positive rate of HBsAg, HBsAb, HBcAb of male is13.51%、56.9%、39.3%. The adjusted positive rate of HBsAg, HBsAb, HBcAb of female is10.6%、57.0%.40.2%. The rate of elevated ALT is8.2%(12.0%in male,5.8%in female). The rate of elevated ALT among the group over30years old with HBsAg positive is0.6%. The epidemic situation between different islands has significant diversity.
Conclusion
According to three national Viral hepatitis serum epidemiological investigations in1979,1992and2006separately, Chinese Hepatitis B surface antigen(HbsAg) carrier has a downward trend with years. Comparing to the result of the investigation in2006, the hepatitis B prevalence of Zhejiang province also has a obvious decline. The hepatitis B prevalence of island areas (Zhoushan and Yuhuan), however, is still beyond average of Zhejiang province. For purpose of droping national hepatitis B prevalence to low level, the government should give vaccination to more people, put more money down on the vaccination, especially to people whose age are above20and have negative result of HBV markers, as well as high risk group who haven't already vaccinated since1992. What's more, comparing to plain region of China, the government ought to focus more on Hepatitis b transmission condition on active floating population in island regions.
Part B:Hepatitis B seroepidemiological survey and stratification analysis
Object:
The hepatitis B vaccine immunization program has been carried out for20years. To understand the prevalence of serological markers among hepatitis B infections in Zhejiang Province, we made a Hepatitis B seroepidemiological survey and further did stratification analysis among the screened hepatitis B infections in insular areas, controlled them to those in plain areas (further detect hepatitis B three-line quantitative HBV-DNA, liver function, alpha-fetoprotein of AFP, B super). Our aim is to understand the epidemic status and the influencing factors of e antigen between different geographical backgrounds and the correlation between serological markers and HBV-DNA and ALT, which is in order to get the latest data to guide the treatment and prognosis of the groups.
Method:
(1) Stratified clustered-random sampling in different stages were adopted in this study. First, in Shaoxing County and Yuhuan County, which are on behalf of the two major landforms (plains and islands) in Zhejiang Province, we divided all township/street into three layers of high, medium and low, based on the economic level. Select one township/street in each layer randomly. Secondly, select three villages/communities randomly again in every town/street, based on the economic level. In totally, six townships/streets were taken, in which18villages/communities were selected. A total of8439effective objects were surveyed.
(2) The questionnaire survey used the unified questionnaire by the method combined concentrated and households, carried out by the professional investigators face-to-face. Serum samples of each participant were collected at the same time, separated. Then send to test related indicators in cryopreservation.
(3) Using fluorescence quantitative PCR, real-timely, dynamicly monitor the HBV-DNA load in gene diagnostic laboratory which is certificated by the Ministry of Health. The machine is the FO-33A PCR instrument offered by Hangzhou Bo Japan Science and Technology Co., Ltd. and reagents were purchased from ACON Biotech (Hangzhou) Co., Ltd.. Meanwhile, serological markers were measured by enzyme-linked immunosorbent assay (ELISA). The enzyme-linked immunosorbent assay kits were produced by Hangzhou aicon Biotechnology Company. Operation was in strict accordance with the kit instructions and the results were read and record by the microplate reader (MULTISKAN MK3). In addition, select the Beckman CX7automatic biochemical analyzer to test ALT, which was purchased from Beijing Leadman Biochemistry Co., Ltd..The results were judged by standards of the kit.
(4) Adopt the EpiData3.1software to create a survey database and the data was entered in strict accordance with the requirements of the double-entry. Use the statistical software SPSS13.0recommended by WHO to conduct statistic. Statistical methods using the chi-square test and inspection standards for bilateral a=0.05.P<0.01was considered significant difference.
Result:
Respondents were HBsAg positive, in which the proportion of40-49year-old crowd was the highest, at33.2%; HBeAg positive rate was18.5%, of which, the population that less than20years old and older than70-year-old crowd, their positive rates were60%and9.2%each. The HBeAg positive rates of men and women were21.9%and14.7%each. Data was significantly different. In Yuhuan and Shaoxing, HBeAg positive rates were21.9%,12.9%. Both have significant difference. HBV-DNA positive rate was91.0%among HBeAg-positive people and was45.4%among HBeAg negative people, which was significantly different. The HBeAg positive rates in population, which HBV-DNA amounts were less than103,103～105,105～107,>107were3.6%,6.0%,41.1%,94.0%. There were a lot of differences of HBeAg positive rates in the populations of the different levels of hepatitis B viral load. Do the Spearman rank correlation analysis with the HBV-DNA and HBeAg and find linear relationship (p <0.01) between the two, but weak correlation (r=0.394<0.4). Do Spearman rank correlation analysis with HBV-DNA and HBeAg among HBeAg-positive patients, find the linear relationship (p<0.01), and it is a strong correlation (r=0.777>0.7). In the population of HBeAg positive, the ALT elevating and the ALT normal people, their HBV-DNA positive rates were95.4%、86.4%respectively, which was significantly different; in the population of HBeAg negative, the ALT elevating and the ALT normal people, their HBV-DNA positive rates were59.6%、41.5%, which was significantly different.
Conclusion:
Compared with the results of investigation made in1992of Zhejiang province, the age structure of the hepatitis B has largely back goes on to40-49, which prompted the Government that it is important to strengthen the coverage of health examination, which includes the HBV detection, and penetration of health education for the40-49's rural population, in order to detect and treat disease early. Although studies have shown that there is linear relationship between the HBV-DNA and HBeAg, in the clinical, doctors need to consider HBV-DNA and HBeAg amount integratedly, especially the people which HBeAg negative but the HBV-DNA level high. Combining the HBeAg, HBV-DNA and ALT could make comprehensive evaluation of viral replication and the reactions of the body. In no condition to using the PCR method for the quantitative detection of HBV-DNA, HBeAg and ALT levels could be regarded as leading indicators to judge the severity of HBV activity and infectious.
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