不同剂量国产重组酵母乙型肝炎疫苗成年人免疫效果及影响因素研究

Objective To evaluate the immuno-effect and related influencing factors on 10 μg and 20 μg Chinese hamster ovary (CHO) cell hepatitis B vaccine, using the randomized double-blind controlled trials in adult population. Methods A total of 642 adults aged 18-45 years old, non-vaccinated against hepatitis B, and negative on five blood indicators for hepatitis B, were selected as the study objects from four districts in Beijing. The study objects were randomly divided into two groups, and then accepted 10 tg and 20 μg recombinant CHO hepatitis B vaccination by 0-1-6 month schedule. Influencing factors were investigated by means of questionnaire. Blood samples were collected one month after the third dose of vaccination. Anti-HBs level was detected by Abott chemiluminescence detection method. For the anti-HBs negative person, fluorescent quantitative PCR method was used to find out if the person had been infected with HBV. Logistic regression analysis was used to find out the influencing factors of anti-HBs seroconversion on every studied subject. Results The anti-HBs seroconversion rates on 10 μg and 20 μg dose groups were 88.8%(95%CI: 85.4%-92.2%) and 95.3%(95%CI: 93.0%-97.6%)respectively. Taking the anti-HBs level＜100 mIU/ml as the low/non-response standard, the low response and non-response rates were 34.3% and 17.4% respectively. The geometric mean titers(GMT)of anti-HBs were 173.42 mIU/ml for the 10 μg dose group and 588.51 mIU/ml for the 20 μg dose group. Data from the Multivariate analysis showed that: diabetes, spouses infected with hepatitis B virus and old age were unfavorable factors for anti-HBs Seroconversion. 20 μg dose of the vaccine was conducive to seroconversion.Conclusion 20 μg CHO hepatitis B vaccine seemed better than 10 μg CHO hepatitis B vaccine while many factors need to be taken into account for evaluation on hepatitis B vaccines.     

2018年开封市中小学生乙肝防治知识认知状况及影响因素分析

OBJECTIVE To understand the cognitive status and influencing factors of hepatitis B prevention knowledge among primary and secondary school students of Kaifeng City in 2018, so as to provide a good guarantee for improving students’ health awareness and disease prevention knowledge. METHODS A questionnaire survey was conducted among primary and secondary school students in Kaifeng from May to July 2018 by stratified sampling and cluster sampling. The questionnaire was provided by China Liver Prevention Foundation. Questionnaire survey mainly analyzed in-depth knowledge about hepatitis B among primary and secondary school students in Kaifeng City, the score of hepatitis B related knowledge among primary and secondary school students of different ages, and the influencing factors of knowledge about hepatitis B were analyzed. RESULTS The awareness of hepatitis B related knowledge among primary and secondary school students in Kaifeng was generally low, with a total awareness rate of 47.84%. The awareness rate of knowing hepatitis B was 82.91%, which was the highest. Secondly, the awareness rate of timely vaccination of hepatitis B vaccine after birth was 73.73%. The lowest awareness rate was that there was no specific drug for hepatitis B at present, which was 13.82%. Different characteristics of primary and secondary school students had different scores of hepatitis B knowledge. Ethnic group, age, educational level and household registration had an impact on the score of hepatitis B related knowledge (P<0.05), while gender had no effect on the score of hepatitis B related knowledge (P>0.05). Multivariate linear regression analysis was used to analyze the influencing factors of knowledge about hepatitis B. It found that age and household registration were the factors influencing the score of knowledge about hepatitis B among primary and secondary school students. CONCLUSION It was very important for the prevention and treatment of hepatitis B to strengthen the propaganda and education of hepatitis B prevention knowledge among primary and secondary school students, to do a good job in propaganda of hepatitis B transmission channels and non-transmission channels, and to find a more scientific and reasonable health education mode.     

2789例10岁以上儿童重组乙型肝炎疫苗加强免疫效果评价

目的 比较不同重组乙型肝炎(乙肝)疫苗加强免疫效果.方法 选择1周岁内完成血源乙肝疫苗基础免疫的10岁以上儿童2789例,分别接种4种国内常用的不同重组乙肝疫苗,分为A、B、C、D4组,采集血清,使用化学发光法检测HBsAg、抗-HBs、抗-HBc,仅抗-HBs阳性者接种1剂次、抗-HBs阴性者接种3剂次相应疫苗,免疫1个月后采血检测抗-HBs.结果 加强免疫前、免疫1剂次及3剂次后A、B、C、D 4组抗-HBs阳性率分别为36.43%、37.59%、42.91%、46.46%;89.20%、91.52%、90.96%、85.45%;99.12%、99.47%、98.87%、98.85%;加强免疫前、免疫1剂次及3剂次后两两之间抗-HBs阳性率差异均有统计学意义(P值均＜0.05).抗-HBs阴性者加强免疫1剂次、3剂次后,抗-HBs阳转率分别为83.01%、86.41%、84.16%、72.82%;98.62%、99.16%、98.03%、97.84%;与抗-HBs阳性者加强免疫1剂次相比,4组抗-HBs阳转率差异均有统计学意义(P＜0.05).抗-HBs阳性者加强免疫1剂次后几何平均滴度(GMT)分别为2853.21、6254.23、3581.40、3021.32 mIU/ml.抗-HBs阴性者加强免疫1剂次、3剂次后4组GMT分别为273.08、648.52、387.87、245.36 mIU/ml;632.30、2341.14、563.97、394.08 mIU/ml.结论 采用上述4种重组乙肝疫苗对抗-HBs阳性的10岁以上儿童加强免疫1剂次、对抗-HBs阴性的10岁以上儿童加强免疫3剂次,免疫效果良好.

Abstract：

Objective To study the efficiency of booster immunization with different recombinant hepatitis B vaccines.Methods 2789 children aged over 10 years who had completed the basic immunization of hepatitis B vaccine under 1 year old were selected.All the sampled children were classified into four groups (A,B,C and D) and immunized with different hepatitis B vaccines produced by different campanies respectively.Before booster immunization,their blood plasma specimens were detected for hepatitis B virus (HBV) surface antigen (HBsAg),antibodies to HBV surface antigen (anti-HBs) and antibodies to HBV core antigen (anti-HBc) by chemiluminescence.In each group,the anti-HBs positive children were immunized with one dosage and anti-HBs negative children were immunized three dosages of the same vaccine.Their blood specimens were collected again after 1 month,and detected for anti-HBs.Results The anti-HBs positive rates of A,B,C and D group were 36.43%,37.59%,42.91% and 46.46% respectively before immunization while 89.20%,91.52%,90.96% and 85.45% respectively after immunization with one dosage,99.12%,99.47%,98.87% and 98.85% respectively after immunization with three dosages.The differences of anti-HBs positive rates in the four respective groups showed statistical significances between any two rates of pre-immunization,post-immunization with one dosage and post- immunization with three dosages (all P＜0.05).The anti-HBs positive conversion rates of four groups were 83.01%,86.41%,84.16% and 72.82% respectively after immunization with one dosage.The anti-HBs positive conversion rate of four groups were 98.62%,99.16%,98.03% and 97.84% respectively after immunization with three dosages and the difference of positive conversion rates in each group showed statistical significances between booster immunization with one dosage and booster immunization with three dosages.The average GMTs in anti-HBs positive children in the four groups were 2853.21,6254.23,3581.40 and 3021.32 mIU/ml respectively after immunization with one dosage.The average GMTs of anti-HBs negative children in the four groups were 273.08,648.52,387.87 and 245.36 mIU/ml respectively after immunization with one dosage,and were 632.30,2341.14,563.97 and 394.08 mIU/ml respectively after immunization with three dosages.Conclusion Our data showed that it would be suitable to anyone to use the four vaccines for anti-HBs positive children aged over 10 years with one dosage and for anti-HBs negative children aged over 10 years with three dosage booster immunization.     

The immunogenicity and safety of 10 μg recombination yeast hepatitis B vaccine applied in expanded population

Objective To assess the feasibility of the 10 μg recombination yeast hepatitis B vaccine in the expanded applicable population group aged 5-18. Methods People with both HBsAg and anti-HBs negative were selected to take two-stage clinical experiment and the safety and immunogenicity were observed. Safety observation was conducted in 925 subjects, while 568 for immunogenicity. The observation group (aged 5-18) included 493 subjects, and (age>18) 75 enrolled in control group. For the observation group,there were three sub-groups including a child group (141, aged 5-6), early youth group(177, aged 12-13), and youth group (175, aged 16-18). Both groups were administered with 10 μg recombination yeast hepatitis B vaccines with 3 doses at 0 month, 1st month,6th month. To assess the immunogenicity,the vaccination reactions were observed during the following 4 weeks in order to assess the vaccine safety. The blood samples were taken during 4-6 weeks after fully vaccinated, and then anti-HBs were tested with RIA and analyzed by comparing the positive rate of anti-HBs,the geometric mean titer(GMT) and the protective rate between the two groups. Results Both observation and control group didn't show any general reactions,adverse events following immunization(AEFI) or coincidental cases when observed at 0. 5 h,6 h,24 h,48 h, 72 h, 1 week,2 weeks,3 weeks,4 weeks after being vaccinated. The result of serum test showed, the positive rates of child group, early youth group, youth group and control group were respectively 100. 00% (141/ 141),97.18% (172/177), 98. 29% (172/175) and 89. 33% (67/75); the GMTs of anti-HBs were respectively 440. 28,875.38,467.80,131.06 U/L; the protective rates were respectively 100. 00% (141/ 141), 97.18%(172/177), 97.14% (170/175) and 86. 67% (65/75). The positive rate, GMT and protective rate of the experimental group were all higher than that of control group(χ2<,positive rate>=12.77,5.12, 7.99; tGMT=3.89,4.13,5.91;χ2protective rate>=16. 81,8.60,8.44;P< 0.05). Conclusion This vaccine could be expanded to 5-18 year-old population with safety and effectiveness, the positive rate and protective rate of anti-HBs were both higher than that of control group.     

急性乙型肝炎临床特征和病毒标志物动态变化分析

Objective To explore the dynamic change of viral marker and clinical features in acute hepatitis B (AHB)and distinguish AHB from chronic hepatitis B(CHB) in acute onset. Methods Viral marker, HBV DNA in serum and clinical features were analyzed in 105 patients with AHB (AHB group) and 102 patients with CHB in acute onset (CHB group) between 2005 and 2009. Results There was no statistical difference in the mean levels of ALT, TBil, HBsAg, HBeAg and HBV DNA between AHB and CHB group on admission. However, the titer of auti-HBc-IgM in AHB group was(26.34 ±3.74)S/CO, which was obviously higher than that in CHB group, which was( 14.46 ± 3.10)S/CO, there was a statistical difference between the two groups( P < 0.05). After 2 weeks treatment, the levels of ALT and TBil in AHB patients decreased (1540.50±225.54)IU/L and (103.60± 46.48) μmol/L respectively, the decreased levels in AHB group were high compared to CHB group; the levels of HBsAg, HBeAg and HBV DNA in AHB group decreased (2558.46 ±644.26) IU/mL, (420.20± 63.20) S/CO and (4.53± 1.42) log10copies/mL respectively, and the levels decreased obviously compared to CHB group (P < 0.05). The decreased level of anti-HBc-IgM in AHB group was no statistical difference to CHB group after 2 weeks treatment (P > 0.05). 19.04% of the AHB patients were HBV DNA negative seroconversion before they were hospitalized. The level of HBsAg and HBeAg in AHB group declined quickly. Separately, 90.47% and 94.24% of the AHB patients had HBsAg and HBeAg seroconversion at the end of follow-up in AHB group. The level of ALT in AHB decreased quickly but its normalization was slower than the clearance of HBV. Conclusions There is no difference in viral marker, HBV DNA and clinical features between AHB and CHB in acute onset patients on admission, but the recovery of liver function in AHB is obviously after treatment. Anti-HBc-IgM (≥20 S/CO), dynamic change and seroconversion viral marker, ALT ≥20×ULN and recovery can be used to differentiate AHB from CHB in acute onset.     

慢性乙型肝炎患者配偶乙型肝炎病毒感染状况调查和分析

Objective To evaluate the influence of daily contact on HBV infection between hepatitis B virus carriers and their spouses by investigating the infection situation after marriage. Methods Premarital HBV carriers of serum HBV DNA positive were enrolled, family history, the histoty of blood donation, blood transfusion, drug abuse,physical examination, premarriage medical check, extramarital sex and hepatitis B vaccine were investigated in their spouses. Couples who were infected before marriage or vaccined with HBV vaccine were excluded. 68 couples were enrolled with an average marriage time of 12.5 years (0.5-35 years), their HBV serum markers and quantitative were performed. Results In the 68 couples, 54(79.4%) spouses were serum HBV marker positive, of the 54 spouses, 4 were HBV DNA positive. The chronic rate of HBV infection in the spouses was 7.4%, and was similar to the rate in general population(5%-10%). 48(88.9%) spouses were anti-HBs positive, the positive rate was similar to the rate in vaccinated population (85%-90%). Male spouses with at least one HBV marker positive were 22 cases (22/24), occupied 91.7% , female spouses were 32(32/44), occupied 72.7%, there was no difference between the male and female spouses(χ2 = 2.681, P > 0.05). Conclusions Whether HBV carriers' spouse infected with HBV is not correlated with marriage time, gender and HBV DNA level of carriers. HBV infection rate of the healthy people increases after marriage with HBV carriers, but the rate of chronic HBV infection is not increased obviouly.     

急性乙型肝炎临床特征和病毒标志物动态变化分析

Objective To explore the dynamic change of viral marker and clinical features in acute hepatitis B (AHB)and distinguish AHB from chronic hepatitis B(CHB) in acute onset. Methods Viral marker, HBV DNA in serum and clinical features were analyzed in 105 patients with AHB (AHB group) and 102 patients with CHB in acute onset (CHB group) between 2005 and 2009. Results There was no statistical difference in the mean levels of ALT, TBil, HBsAg, HBeAg and HBV DNA between AHB and CHB group on admission. However, the titer of auti-HBc-IgM in AHB group was(26.34 ±3.74)S/CO, which was obviously higher than that in CHB group, which was( 14.46 ± 3.10)S/CO, there was a statistical difference between the two groups( P < 0.05). After 2 weeks treatment, the levels of ALT and TBil in AHB patients decreased (1540.50±225.54)IU/L and (103.60± 46.48) μmol/L respectively, the decreased levels in AHB group were high compared to CHB group; the levels of HBsAg, HBeAg and HBV DNA in AHB group decreased (2558.46 ±644.26) IU/mL, (420.20± 63.20) S/CO and (4.53± 1.42) log10copies/mL respectively, and the levels decreased obviously compared to CHB group (P < 0.05). The decreased level of anti-HBc-IgM in AHB group was no statistical difference to CHB group after 2 weeks treatment (P > 0.05). 19.04% of the AHB patients were HBV DNA negative seroconversion before they were hospitalized. The level of HBsAg and HBeAg in AHB group declined quickly. Separately, 90.47% and 94.24% of the AHB patients had HBsAg and HBeAg seroconversion at the end of follow-up in AHB group. The level of ALT in AHB decreased quickly but its normalization was slower than the clearance of HBV. Conclusions There is no difference in viral marker, HBV DNA and clinical features between AHB and CHB in acute onset patients on admission, but the recovery of liver function in AHB is obviously after treatment. Anti-HBc-IgM (≥20 S/CO), dynamic change and seroconversion viral marker, ALT ≥20×ULN and recovery can be used to differentiate AHB from CHB in acute onset.     

The Influence of Therapeutic HBsAg Vaccine on Immune Responses in Mice

Objective To investigate the effect of various doses of HBsAg vaccine on cellular immune responses in mice. Methods Mice were immunized with one or two low, medium or high doses of HBsAg vaccine. T cell proliferation was tested by [^3H] thymidine incorporation. Secretion of IL- 2 and IFN - γ into culture supematants, and the concentration of serum anti - HBsAg IgG2a, were determined by ELISA. The lactate dehydrogenase method was used to detect the cytolytic activity of antigen - specific T cells. Results Primary immunization with medium- or high - dose HBsAg significantly enhanced T cell proliferation （ P 〈 0.01 ）, secretion of IL - 2 and IFN - γ/（ P 〈 0.05 for each ）, and anti - HBsAg IgG2a （ P〈 0.05）. Booster immunization further enhanced ＇all of these parameters. Booster, but not primary, immunization with low - dose HBsAg significantly enhanced all of these markers of cell - mediated immunity. Significant CTL activity was observed in all three groups of immunized mice and was independent of dose. Conclusion In mice, HBsAg vaccine induces cellular immune responses, boosts production of Thl - specific cytokines, and upregulates both cytolytic and noncytolytic immune responses. These findings suggest that this vaccine may be useful in treating patients with chronic hepatitis B.     

北京市某传染病医院14 398例乙型肝炎住院患者特征及费用分析

目的 了解北京市某传染病医院2002-2007年14 398例次乙型肝炎(乙肝)出院患者人口学和疾病特征及住院费用,分析住院总费用相关影响因素.方法 采用描述性分析方法 分析乙肝出院患者人口学和疾病特征及住院费用;应用多元线性回归后退法分析影响总住院费用的凶素.结果 乙肝住院患者男性高于女性(2.9:1);平均年龄45.2岁.乙肝出院患者死亡比例为7%,平均年龄为55岁.住院患者平均费用为16947.91元;其中肝硬化患者费用最高,病毒携带患者费用最低.费用构成中药费所占比重最大(62.4%);医疗费用的影响因素为病种、住院时间、疾病程度(是否手术、合并及伴随疾病)、患者人口学特征、居住地区.结论 乙肝住院患者男性比例高于女性;如果发病初期未得到有效控制,发展为慢性肝炎、肝硬化或肝癌,合并症多,预后较差,相应的医疗费用增加.医疗费用不仅与疾病的病种有关,还与疾病的复杂程度、患者特征相关.

Abstract：

Objective This article was to focus on the study of patient's profile,type and distribution of the disease and the related factors contributing to medical cost on 14398 cases of hospitalized patients with hepatitis B from a hospital of infectious diseases located in Beijing,in order to provide basic information on optimizing the prevention and treatment strategies.Methods Information on hospital admission of patients、with hepatitis B was collected and SPSS 16.0 statistics software package was used to analyze the profile,disease patterns distribution,structure of medical costs and main contributors related to medical costs.Results Through analysis,we found that the proportion of male patients was much bigger than that of female patients,with ratio as 2.9.The average age of patients with hepatitis B was 45.2 years old.The treatment process was time consuming,and the mortality rate was hiigh.Our data showed that the mortality of hospitalized patients was up to 7%and the average age of death was 55 years old.Hepatitis B infection was easy to develop into chronic,cirrhosis and even liver cancer,Fortreatment cost,the largest cost share was the drugs being used which accounted for 62.4%.In terms of health care costs,it was high and the total cost of hospitalization was related to the following factors:days of hospitalization;complexity of the disease condition and the factors as the severity of the disease complications as surgery,frequencies of rescue,type of disease etc;basic information of the patients as age,occupation,origin.Conclusion Compared with other diseases,the proportion of male patients with hepatitis B was much higher than that of the famale.Hepatitis B had a longer duration and difficult,treatment high cost of medical care,poor prognosis,high mortality rate;Cost control,Call not simply fixcd by single disease,but by complexity of the disease and patient characteristics.     

广州市乙型肝炎相关疾病住院病例无形费用及其影响因素分析

目的 了解乙型肝炎(乙肝)相关疾病住院病例年均无形费用以及占总费用的比例和影响因素,探讨无形费用的调查方法.方法 利用自制结构式问卷,对乙肝相关疾病住院病例进行面对面询问,比较支付意愿法三种引导技术获得的无形费用数值特征;采用多元线性回归分析,探讨无形费用的影响因素.结果 开放式估价和重复投标式相结合调查得到564例乙肝相关疾病患者年无形费用均值为54 320.4元,占总费用的比例为53.0%,高于直接费用和间接费用所占比例(分别为38.5%和8.5%),即乙肝相关疾病无形费用占总费用的比例较高.无形费用占患者和家庭年收入的比例分别为262.6%和67.6%,形成沉重的经济负担.开放式估价、开放式估价和重复投标式结合、支付卡式三种引导技术的反映率分别为55.9%、76.6%和74.7%;综合比较发现,开放式估价和重复投标式结合技术获得的结果较为合理.乙肝相关疾病患者的无形费用高低与疾病的严重程度关系不明显;无形费用12个可能的影响因素中,医院类型和是否购买商业医疗保险进入多元线性回归模型.结论 在降低乙肝相关疾病直接和间接费用的同时,应采取措施降低其无形费用;支付意愿法中开放式估价和重复投标式结合作为乙肝相关疾病无形费用调查的引导技术较为可靠.

Abstract：

Objective To estimate the intangible cost and associated factors on patients with hepatitis B-related diseases, so as to explore the differences of the three elicitation techniques on the health economics-related information by trained investigators, using a structured questionnaire. WTP was employed to estimate the intangible cost while an open-ended question format, together with iterative bidding game and payment card were respectively used to elicit WTP for the hypothetical cure of hepatitis B-related diseases. A Multiple linear stepwise regression model was determined to identify those factors potentially affecting the intangible cost. Results A total of 564 subjects from 641 patients with hepatitis B-related diseases were identified for the inclusion of this study. The average annual intangible cost of patient with hepatitis B-related diseases was 54 320.4 Yuan (Ren Minbi).The intangible cost accounted for 53.0% of the total cost, which was much more than the proportions of the direct and indirect costs (38.5% and 8.5%, respectively). Among annual personal and the household income of the patient, proportions of intangible cost were 262.6% and 67.6% respectively,suggesting that the patients were under huge spiritual and psychological pressure. Response rate of the approach, combined open-ended questions with iterative bidding game, was the highest (76.6%) among the three elicitation formats. Considered the characteristics of data being gathered, the approach seemed to be more reasonable. Further studies were needed to examine the results yielded from other WTP elicitation formats. We also noticed that the progression of disease was associated with the increase of direct and indirect costs, but not with the intangible cost. Data from the multiple linear stepwise regression analysis indicated that the types of hospital and commercial medical insurance were significantly different in explaining the variation of the intangible cost. Conclusion Measures should be taken to reduce the intangible cost of hepatitis B-related diseases. The approach regarding the combination of open-ended questions with iterative bidding game should be recommended when carrying our further WTP studies of this kind.