| [Background]Hepatitis B Virus (HBV) infection is one of public health problems that seriously harm residents’health. HBV chronic infection can transform into liver cirrhosis or liver cancer and bring heavy disease burden to the patients. China has a high prevalence of hepatitis B and HBsAg positive rate is also high for a long time. Every year, the number of hepatitis B cases reported is more than most other notifiable diseases. Once HBV infection turns into a chronic process, it is difficult to clean the virus for body and most infected individuals bring HBsAg lifelong. So decreasing hepatitis B incidence is one of the important measures to prevent and control hepatitis B in China.Hepatitis B immunization is the most economical and effective method to protect susceptible population and to prevent HBV infection. Population HBsAg positive rate in China have declined remarkably, especially in the children under 15 years old, benefiting from the long-term implementation of newborns’hepatitis B immunization strategy. With HBV infection in children being controlled effectively in our country, adult hepatitis B prevention and control draws more and more attention. However, there is no perfect adult hepatitis B immunization strategy at national level. Nowadays, hepatitis B cases of incident in Chain occurred in adult principally, so making, perfecting and implementing adult hepatitis B immunization strategy are important measures to decline hepatitis B incidence and HBsAg positive rate in China.Antibody concentration may decline with time in the individuals who have responses to hepatitis B immunization already, so it always be an important issue focused by researchers and first-level health workers that whether it is needed to carry out hepatitis B reinforce immunization and when to carry out. Following up immune memory persistence in the adult after primary vaccination has theoretical and practical significance for making and perfecting adult hepatitis B immunization strategy.[Objectives]1. To compare antibody positive rates, antibody concentrations, breakthrough infection rates in adult cohorts that have different immune responses to hepatitis B primary vaccination in 1 month and 5 years, and analyze their influencing factors. To study the trends of specific humoral immunity levels with time in 5 years after primary vaccination, and analyze their influencing factors.2. To compare antibody positive rates, antibody concentrations, breakthrough infection rates in 1 month and 5 years after primary vaccination with different kinds of hepatitis B vaccines, and analyze their influencing factors. To study the trends of specific humoral immunity levels with time after primary vaccination, and analyze their influencing factors.3. Synthesizing the results above, to analyze the long-term effects in adult after hepatitis B primary vaccination, and analyze their influencing factors. To study if reinforce immunization is needed when the adult has a normal immune response to hepatitis B vaccination and to provide suggestions about reinforce immunization.[Methods]In 2009, with the support of "study of immune and prevention strategy of hepatitis B in China" (2008ZX10002-001), a state key scientific research program in 11th Five-Year Plan, a group in Center for Disease Control and Prevention of Shandong Province launched the research. They selected 24237 adults aged from 18 to 49 as investigation objects by cluster random sampling from 79 villages, belonging to 3 towns in Zhangqiu, Jinan. The villages had low population mobility and had never recognized the adult hepatitis B immunization.Investigation objects finished questionnaires and their venous blood samples were tested for concentrations of HBsAg, anti-HBs and anti-HBc. The individual whose test results were all negative would be regarded as trial objects. All trial objects were divided into 4 groups by cluster sampling and a country was regarded as a cluster. Individuals in one group were injected a kind of hepatitis B vaccine according to "0-1-6" immune procedure and were tested antibody concentrations after vaccination. If someone had no response or low response to vaccination, he would be injected another kind of hepatitis B vaccine and tested. According to questionnaires and the results of tests, all trial objects were divided into four groups as cohorts:high response to primary vaccination group (Cohort 1), normal response to primary vaccination group (Cohort 2), no response to primary vaccination group (Cohort 3), low response to primary vaccination group (Cohort 4). Every cohort had 1000～3000 objects. Aim of this research is to follow up immune memory persistence of 4 cohorts in 5 years after hepatitis B primary vaccination. Providing the agreements of all investigation objects, researchers collected their information through questionnaires and collected venous blood samples to test concentration of anti-HBs and anti-HBc, as well as HBsAg if anti-HBs was negative. They analyzed the results of following-up, and evaluated long-term immune effects after hepatitis B vaccination in different cohorts synthetically.Enzyme-linked Immunosorbent Assay (ELISA) was used in blood sample tests to select trial objects. Chemiluminescence Microparticle Imunoassay (CMIA) was used in blood sample test after hepatitis B vaccination. Epidata was used to input data and SPSS or STATA to analyze. x2 test was used to compare ratios in different groups. Normal measurement material t test, u test and single factor ANOVA were used to compare Geometric Mean Concentration (GMC) in different groups. Researchers regarded age, gender, kinds of vaccines in primary immunization, GMC level and other factors as dependent variables separately and used multi-factor logistic model as well as multi-factor linear regression model to analyze influencing factors of antibody positive rate(the proportion of anti-HBs≥10mlU/mL), GMC(Geometric Mean Concentration)and breakthrough infection rate(the proportion of positive HBsAg and/or positive anti-HBc) in following-up.[Results]1. Antibody positive rate in following up:There are 2787 individuals in four groups totally, including 1943 individuals that have positive anti-HBs (anti-HBs≥ lOmlU/mL), and anti-HBs positive rate is 69.72%. This positive rate in 5 years after primary vaccination declined by 17.51%compared with that in 1 month after primary or secondary vaccination (T1,87.23%,2431/2787). For four groups, anti-HBs positive rates in following up are 73.06%,73.61%,66.16%,55.90% by the turns of high response, normal response, low response and no response group. Normal response group has the highest anti-HBs positive rate and no response group has the lowest. The differences of anti-HBs positive rates in four groups are statistically significant (x2=46.937, P<0.001).2. GMC in following up:For four groups, antibody GMC in 5 years are 35.84mIU/mL (95%CI:32.80-40.04),34.40mIU/mL (95%CI:29.79-38.90), 27.70mIU/mL (95%CI:23.13-33.18),15.03mIU/mL (95%CI:12.22-18.49) by the turns of high response, normal response, low response and no response group. High response group has the highest antibody GMC and no response group has the lowest. The differences in four groups are statistically significant (F=283.506, P<0.00\).3. Factors influencing antibody positive rate and GMC in following up:for four groups, antibody positive rates increase with the increase of antibody concentration after primary or secondary vaccination (P<0.05). For high response, normal response, and no response group, following-up antibody GMC increase with the increase of antibody concentration after primary or secondary vaccination (P<0.05), and in no response group, antibody concentration after secondary vaccination has more influence on following-up antibody GMC. For low response group, following-up antibody GMC increase with the increase of antibody concentration after secondary vaccination (P<0.05) and is independent to antibody concentration after primary vaccination (P>0.05). For high response and normal response group, low response group, following-up antibody positive rates and GMC in subgroup that received 20μg HepB-CHO in primary vaccination are higher than other subgroups (P<0.05). For no response group, following-up antibody GMC in subgroup that rejected 20μ HepB-CHO is higher than other subgroups (P<0.05). For low response group, following-up antibody GMC in subgroup that rejected 20μg HepB-SC in secondary vaccination is higher than other subgroups (P<0.05). But antibody positive rate and GMC in no response group and antibody positive rate in low response group are all unrelated to vaccines types in secondary vaccination (P>0.05).For low response group, antibody positive rate and GMC are related to BMI, and results in normal weight subgroup are higher than that in obesity subgroup. But these results are not found in other groups. It has not been found in this research that antibody persistence is related to gender, BMI, history of tobacco and alcohol and other factors (P>0.05).4. Breakthrough infection rate in following up:In all 2787 individuals, there are 175 breakthrough infection cases and breakthrough infection rate is 6.28%. This rate in high response and normal response group is 2.55%(74 cases). In low response group, it is 11.72%(62 cases) and in no response group, is 10.96%(39 cases). The breakthrough infection rate in low response and no response group is higher than that in normal response and high response group, and the difference has statistical significance (x2=58.28, P<0.001).5. Factors influencing breakthrough infection:For normal response, high response and no response group, breakthrough infection rates are unrelated to age when primary vaccination, gender, BMI, history of tobacco and alcohol, vaccine types of primary vaccination, vaccine types of secondary vaccination (P>0.05). For low response group, breakthrough infection rate is related to vaccine types of primary vaccination, vaccine types of secondary vaccination and BMI (P<0.05). This rate in subgroup that received 20|μg HepB-CHO in primary vaccination is higher than subgroup that received 20μg HepB-SC. This rate in subgroup that received 20μg HepB-CHO vaccine in secondary vaccination is higher than subgroup that received lOμg HepB-SC and 20μg HepB-SC. This rate in lower weight and normal weight subgroup are higher than obesity subgroup. Breakthrough infection rate decrease with the increase of anti-HBs concentration after hepatitis B immunization. Breakthrough infection rates in high response and normal response group are mainly influenced by antibody concentration after primary vaccination, and the rates in low response and no response group are mainly influenced by antibody concentration after secondary vaccination.[Conclusions]1. Antibody positive rates in 5 years after hepatitis B immunization in different cohorts can remain in the range of 55% to 75%, and antibody positive rate is relatively high. But antibody GMC sharply decrease, and in 71.55%individuals it is less than 100 mlU/ml and in 30.28%individuals less than l0mlU/ml. In all cohorts, GMCs decrease by more than 90%compared with that after primary or secondary vaccination. The sharp decrease of antibody GMC in following-up population will increase the risk of breakthrough infection.2. In general, antibody stimulated by 20μg hepatitis B vaccine is more persistent than that stimulated by 10μg hepatitis B vaccine. Especially, vaccine types of primary vaccination have more influence on antibody persistence.3. Antibody is more persistent in the population with higher antibody concentration after primary and secondary vaccination. And antibody concentration after secondary vaccination has more influence on individual’s antibody persistence than antibody concentration after primary vaccination if the individual has low response or no response to primary vaccination.4. Breakthrough infection rate in following up is lower in the population with higher antibody concentration after primary and secondary vaccination. And antibody concentration after secondary vaccination has more influence on breakthrough infection rate than antibody concentration after primary vaccination if the individual has low response or no response to primary vaccination.5. It has not been found in this research that antibody concentration and breakthrough infection rate in following up are related to object’s gender, history of tobacco and alcohol, and so on.[Suggestions]1. Considering that antibody stimulated by three agents in secondary vaccination is more persistent in the adults who have low or no response to hepatitis B primary vaccination, this population should receive three agents or higher does vaccine.2. Considering that antibody positive rate and GMC are higher and antibody is more persistent when received 20μg hepatitis B vaccine for primary vaccination, the adult should receive 20μg hepatitis B vaccine in primary vaccination.3. The adults who have special risk of exposure, such as the individual in operating room or laboratory who contact with blood frequently, the individual who receive renal dialyses, the family of HBV chronic infection patients, should reexamine every 3 to 5 years. The individual whose antibody disappear or the titer is less than 100mlU/mL can receive an agent of hepatitis B vaccine for reinforce. The individual whose antibody concentration is lower after primary or secondary vaccination can shorten intervals of reexamination and intervals of reinforce immunization properly in case of breakthrough infection.4. Making perfect adult hepatitis B immunization strategy at national level on the basis of this research as well as domestic and international researches. |
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