慢性乙型肝炎病毒感染孕妇妊娠压力的现状分析

目的深入探讨HBV慢性感染孕妇妊娠压力状况及其特点。方法采用方便取样，使用妊娠压力量表对148例慢性HBV感染孕妇（病例组）以及153例正常孕妇（正常组）进行问卷调查。结果两组孕妇的总的妊娠压力、因子1及因子3的压力处于轻度水平，而因子2的压力处于中度水平；病例组总的妊娠压力及因子2得分高于正常组，差异有统计学意义（P〈0.05），而在因子1、因子3方面的差异无统计学意义（P〉0．05）；两组在因子2的1个条目及因子1中的3个条目上差异有高度统计学意义（P〈0．01），在其他条目上的差异无统计学意义（P〉0．05）。结论HBV感染孕妇在母子健康与安全及孩子出生后的状况方面存在较多担心，应给予有针对性的护理，以有效降低其压力水平，确保母婴健康。     

乙肝免疫球蛋白阻断乙肝病毒宫内感染的系统评价

目的系统评价乙肝免疫球蛋白(HBIG)对乙肝病毒(HBV)母婴垂直传播的阻断效果和安全性。方法计算机检索EMbase(1980～2007.4)、MEDLINE(1996～2007.4)、Cochrane图书馆(2007年第3期)、中国生物医学文献数据库(CBM,1978～2007.4),纳入比较孕期单独使用HBIG与不使用HBIG阻断HBV母婴垂直传播的随机对照试验。由两名评价者独立选择试验、提取资料和进行方法学质量评估。研究数据的统计分析采用Cochrane协作网提供的RevMan4.2.8软件进行。结果最终纳入4个RCT,共359例孕妇。Meta分析结果显示,试验组HBVDNA( )孕妇所生新生儿血HBVDNA( )率为8.65%,对照组为35.06%,其差异具有统计学意义[OR0.17,95%CI(0.09,0.31),P<0.00001]。此外,无论是对孕妇还是胎儿都没有报道与HBIG相关的严重不良反应。结论现有研究结果显示,与空白对照比较,HBIG能有效提高乙肝病毒宫内感染的阻断率,并且无明显药物不良反应。由于本系统评价纳入的RCT质量均为C级且患者例数有限,存在选择性偏倚和发表偏倚的高度可能性,我们期待将来高质量的随机双盲对照试验提供高质量的证据。     

Surface gene mutations of hepatitis B virus among high-risk patients with occult hepatitis B virus infection

Surface gene mutants of hepatitis B virus (HBV) have been reported in a variety of patient groups. Because of limited data regarding these mutations in patients with occult HBV infections; we aimed to determine these mutations among high-risk patients with occult HBV infection. The presence of HBV-DNA was determined in patients with isolated anti-HBc by real-time polymerase chain reaction (PCR). Then, surface gene region was amplified by nested PCR and mutations were analyzed after sequencing. The mutations that resulted in nonfunctional hepatitis B surface antigen (HBsAg) were insertion of single nucleotide in 2 cases, which causes frameshift and single-nucleotide replacement, and premature stop codons at Leu15 and Gly10 in the other 2 cases. Amino acid substitution at amino acid position 207(S207N) was found in the other isolates. Our study suggested that “a” region mutations did not play a major role in HBsAg detection, and other genetic and nongenetic factors may be responsible for failure to detect HBsAg by routine laboratory tests.     

Present and future DNA vaccines for chronic hepatitis B treatment

Introduction: With at least 240 million hepatitis B virus (HBV) carriers worldwide, being at a high risk of cirrhosis and hepatocellular carcinoma (HCC), chronic hepatitis B remains a major public health issue. Because current antiviral treatments are only virostatic, there is an urgent need for the development of innovative anti-HBV strategies leading to the functional cure. In this context, DNA-based vaccines appear as a promising approach.

Area covered: In this review, the authors summarize the pertinent features of DNA vaccines for chronic hepatitis B therapy. They review several technologies that improve DNA vaccines efficacy evaluated in animal models of hepadnaviral infection. They also discuss the clinical trials of therapeutic DNA vaccination initiated in HBV-carrier patients.

Expert opinion: Preclinical studies in HBV transgenic mice, DHBV-carrier ducks and WHV-infected woodchucks, have clearly demonstrated a benefit of DNA vaccine-based combination therapies for chronic hepatitis B treatment. However, the results of clinical trials conducted in HBV patients were rather disappointing and frustrating, as DNA-vaccines have not shown the same efficacy in patients as in animal models. We are convinced that the design of innovative clinical trials based on strategies able to increase DNA vaccine immunogenicity will allow to advance in this challenging field.     

重组(酵母)乙型肝炎疫苗免疫人群效果观察

目的　了解重组 (酵母 )乙型肝炎疫苗用于人群的免疫效果。方法　 1997- 2 0 0 2年 ,在对人群HBV感染指标 (HBsAg、抗 -HBs、抗 -HBc)测定的基础上 ,对易感人群进行重组 (酵母 )乙型肝炎疫苗的接种。2 0 0 3年 ,采用整群随机抽样的方法 ,从研究人群中抽取 5个研究人群 ,进行一般状况和HBV感染指标测定 ,以观察不同年龄、不同接种针次接种重组 (酵母 )乙型肝炎疫苗的免疫效果。结果　不同年龄的易感人群接种重组(酵母 )乙型肝炎疫苗HBsAg、抗 -HBc阳性率明显低于未接种组 ,抗 -HBs阳性率明显高于未接种组。 4 5岁以下人群免疫效果较好 ,抗 -HBs阳性率在 76.29%以上。免疫后 1- 5年 ,HBsAg阳性率维持在 1%以下 ,抗 -HBs阳性率保持在 77.66 %以上。不同接种针次效果不同 ,接种 1针次重组 (酵母 )乙型肝炎疫苗免疫效果较差 ;接种 2针或 3针免疫效果较好 ,抗 -HBs阳性率保持在 75.76 %以上。结论45岁以下易感人群接种重组 (酵母 )乙型肝炎疫苗能够获得良好的免疫效果.     

Prevalence and characteristics of occult hepatitis B virus infection in Japanese human immunodeficiency virus-infected patients

Occult hepatitis B virus (HBV) infection (OBI) is hepatitis B surface antigen (HBsAg) negative but with detectable HBV DNA. Although HIV infection has been reported to be a risk factor for OBI, the prevalence and clinical features of OBI in Japanese HIV infected patients have not been documented. This retrospective, single-center study was conducted to determine the prevalence and characteristic of OBI in Japanese antiretroviral therapy (ART) naïve HIV infected patients. OBI was defined as the presence of serum HBV DNA but without detectable HBsAg. Of the 147 ART naïve HIV infected patients, OBI was detected in 9 (6.1%) patients; 2 (4.3%) of 47 with both anti-HBs and anti-HBc positive, 6 (27.3%) of 22 with anti-HBc alone, and 1 (2.0%) of 50 with both anti-HBs and anti-HBc negative. The mean HBV DNA level was low at 28.7 ± 18.2 IU/mL. The proportion of OBI patients with anti-HBc alone was significantly higher than that of non-OBI patients (66.7% vs 14.5%, P = 0.001). In addition, the prevalence of AIDS (acquired immunodeficiency syndrome)-defining illnesses in the OBI group was significantly higher than in the non-OBI group (77.8% vs 35.5%, P = 0.001). No significant difference was found in the CD4 count or alanine aminotransferase levels of these two groups. This is the first study to reveal the prevalence and clinical features of OBI in Japanese HIV-infected patients. The persistence of anti-HBc alone and AIDS-defining illnesses were associated with the occurrence of OBI in these patients.     

乙肝病毒五项标志物检测的布板法改进及优势分析

目的通过对乙肝病毒(HBV)五项标志物检测方法的改变,可以随机快速定性或定量的检测。方法将原来的大样本单项布板改变成小样本量纵向五联法布板,进行干扰试验和携带污染试验。结果方便了实验操作,各板单列时高含量的HB sA g ,HB sA b ,HB eA g 在测试时均有一定的携带污染率。HB sA g酶标液可使HB sA b,HB eA b,HB cA b检测孔呈阳性。HB sA b酶标液可使HB sA g,HB eA b,HB cA b检测孔呈阳性。HB cA b酶标液可使HB cA b检测孔呈阳性。HB eA b,HB eA b的酶标液对各检测孔均无干扰。由于HB sA g,HB sA b的酶标液对HB sA b,HB sA g的包被孔可以相互干扰,而HB eA g的酶标液对两者均无干扰。高含量的HB sA g ,HB sA b ,HB eA g 血清在测试时均有一定的携带污染率。纵向五联排列每列为同一样本不存在携带污染问题。结论可以提高检测结果的准确性,提高抗干扰能力,提高实验方法的精密度,方便结果的报告,加强批间质量控制,可以随机快速定性或定量的检测HBV五项标志物。     

流式细胞术检测淋巴细胞Fc受体及其对HBV感染者疾病诊断价值的研究

目的建立FcR标记检测方法，探讨FcR的表达在乙型肝炎慢性化过程中的作用。方法制备FITC标记的聚合IgG，标记淋巴细胞表面的FcR，应用流式细胞术分析急性和慢性乙型肝炎患者各病程时期FcR表达的阳性淋巴细胞百分率。结果慢性乙型肝炎患者FcR的表达较对照组和急性乙型肝炎康复患者显著低下（P〈0．01）；急性乙型肝炎患者急性发作期FcR阳性细胞百分率明显高于对照组（P〈0．01）；急性乙型肝炎应用干扰素（IFN）治疗1个月后及完全康复后FcR阳性细胞百分率与正常对照组相一致。结论流式细胞仪检测淋巴细胞FcR表达，有助于判断乙型肝炎患者的病情、估测预后和指导治疗。     

乙型肝炎病毒载量与乙型肝炎两对半之间的关系

目的 探讨乙型肝炎(下称乙肝)病毒(HBV)载量与乙肝两对半之间的关系.方法 891例血清样本采用酶联免疫吸附试验检测乙肝病毒标志物,LightCylcer检测血清HBV-DNA载量.结果 共检出11种血清学模式,乙肝病毒e抗原(HBeAg)阳性和阴性组的病毒载量分别为106.63 copy/ml和103.13 copy/ml,二者差异有统计学意义(P＜0.01).其中乙肝病毒表面抗原(HBsAg)( )、HBeAg( )模式组HBV-DNA阳性率最高(100%),平均病毒载量达107.05 copy/ml,其次为HBsAg( )、HBeAg( )、抗-HBc( )模式组,阳性率为97.0%,平均病毒载量为106.14 copy/ml.结论 HBeAg阳性模式HBV载量高于HBeAg阴性模式,HBeAg阳性可以在一定程度上提示病毒的复制状况.     

血清中HBV-DNA的两种定量PCR方法的比较

目的 比较乙型肝炎病毒脱氧核糖核酸(HBV-DNA)定量测定的两种方法:聚合酶链式反应-酶联免疫吸附测定(PCR-ELISA)法和荧光定量-聚合酶链式反应(FQ-PCR)法。方法 检测了两种方法的灵敏度、批内批间可信度和特异性。结果 PCR-ELISA法和FQ-PCR法在特异性和批内批间可信度方面相似。在85个HBV表面抗原阳性的病人血清中两种方法的检测结果96％保持一致,HBV-DNA血清阳性率分别为84％和80％,其结果取对数后有一定线性关系(r=0.588 9)。PCR-ELISA法的灵敏度比FQ-PCR法高出一个稀释度,PCR-ELISA的最小检测限7.6×10~3拷贝/ml,而FQ-PCR为2.1×10~4拷贝/ml。但FQ-PCR法的技术复杂性要简单得多,分析时间(2 h)比PCR-ELISA(8 h)要短得多。结论 两种方法各有优缺点,每个实验室都应根据各自的需求加以选择。     

我校新生乙型肝炎病毒感染情况分析与对策

目的:了解本校新生乙型肝炎病毒感染状况,为有针对性地制定防治对策提供科学依据。方法:对本校2002~2005年入学新生进行HBsAg检测及ALT检测,并将结果进行统计分析。结果:新生HBsAg阳性率4.23%~5.20%,有逐年下降趋势;男生HBsAg阳性率明显高于女生(P<0.01),农村的新生HBsAg阳性率明显高于城镇新生(P<0.01);乙肝病毒感染模式以"大三阳"和"小三阳"为主。结论:入学新生HBsAg检测及ALT检测的结果反映其乙型肝炎病毒感染和免疫状况,是制定乙肝防治对策和提升学生保健服务的重要依据。     

Hepatitis B virus infection: pathogenesis,reactivation and management in hematopoietic stem cell transplant recipients

Hepatitis B virus (HBV) is a partially double stranded DNA virus that can integrate into host cell chromosomes as covalently closed circular DNA forms. HBV reactivation following hematopoietic stem cell transplantation in recipients with evidence of past HBV exposure, as well as exacerbation of a current HBV infection in HBV carrier recipients, secondary to chemotherapy and post-transplant immunosuppression that affect both humoral and cell-mediated control of HBV infection, are well documented in the literature. Management options include HBV-DNA screening and antiviral prophylaxis. Nucleos(t)ide analogues have been used at the start of chemotherapy and pretransplantation, with the course continuing for 6 months. However, depending on the serum HBV-DNA level, the antiviral agent might be given until a therapeutic end point is reached.     

替比夫定与拉米夫定比较治疗慢性乙肝疗效的系统评价

目的系统评价替比夫定与拉米夫定比较治疗慢性乙型病毒性肝炎的疗效。方法计算机检索PubMed、EMbase、VIP、CBM和Cochrane图书馆,纳入替比夫定与拉米夫定比较治疗慢性乙肝的随机对照试验(RCT),检索时间截止至2010年2月,文种限于中、英文。按照纳入排除标准选择试验并评价质量,而后提取有效数据进行Meta分析。结果共纳入2个RCT,均为A级研究,合计1 699例患者。Meta分析结果显示:所有用于疗效评价的指标,包括治疗应答[RR=1.28,95%CI(1.10,1.48),P=0.001]、ALT复常率[RR=1.12,95%CI(1.01,1.23),P=0.02]、HBV-DNA未检出率(PCR法)或低于检测下限[RR=1.44,95%CI(1.36,1.53),P<0.00001]、原发治疗失败[RR=0.28,95%CI(0.18,0.43),P<0.00001]、病毒突破率[OR=0.38,95%CI(0.32,0.47),P<0.00001]、病毒耐药[OR=0.44,95%CI(0.36,0.55),P<0.00001],替比夫定均优于拉米夫定。结论基于当前临床证据,替比夫定治疗慢性乙肝的疗效优于拉米夫定。但由于纳入研究的随访时间较短,样本量也较小,远期结果有待进一步研究探讨。     

乙肝病毒YMDD区变异后不同抗病毒疗法效果的系统评价

目的系统评价与拉米夫定相关的乙型肝炎病毒YMDD区变异后不同抗病毒治疗方法的疗效和安全性.方法计算机检索MEDLINE (1989～2004.4)、EMBASE (1989～2004.4)和中国生物医学文献数据库(1989～2004.4);手工检索未发表的中文学术会议文献.收集与拉米夫定相关的乙型肝炎病毒YMDD区变异后不同抗病毒疗法的临床随机与半随机对照试验,由两名评价者独立评价和提取资料,并采用Cochrane协作网专用软件RevMan 4.2进行统计分析.结果共纳入5篇随机和半随机对照研究,包括6个试验组284例病人.Meta分析结果显示,拉米夫定 阿德福韦治疗对HBVDNA、HBeAg转阴率及ALT复常率的效果明显优于单独应用拉米夫定,其RR和95%CI分别为16.61(2.29,120.71),6.66(1.23,35.88)和6.26(2.29,17.12).氧化苦参碱 胸腺肽对HBVDNA、HBeAg转阴率明显优于单独应用拉米夫定,其RR和95%CI分别为2.96(1.26,6.93),2.51(1.05,5.98).试验组单独使用阿德福韦与拉米夫定比较,两者在HBVDNA及HBeAg转阴率方面差异无统计学意义[RR 11.00,95%CI(0.65,186.02);RR 7.00,95%CI(0.39,126.92)];干扰素 拉米夫定对HBVDNA转阴率、HBeAg转阴率、ALT复常率优于单独应用拉米夫定,其RR和95%CI分别为3.50(0.90,13.58),4.90(0.70,35.10)和2.80(0.91,8.12);拉米夫定 中药与拉米夫定比较,其HBVDNA转阴率的差异无统计学意义[RR 1.16,95%CI(0.89,1.51)].在治疗过程中出现的副作用主要有:干扰素组产生流感样症状,阿德福韦组有轻度肾脏损伤,拉米夫定组有少数病例出现一过性病情加重.结论乙肝病毒YMDD变异后,阿德福韦 拉米夫定、氧化苦参碱联合胸腺肽等疗法的抗病毒作用及生化指标改善均优于继续单独使用拉米夫定.但由于样本量偏少,随机对照试验的质量普遍较低,对此尚不能得出肯定性的结论,有待扩大样本进一步研究.     

Effect of Pegylated Interferon Plus Tenofovir Combination on Higher Hepatitis B Surface Antigen Loss in Treatment-naive Patients With Hepatitis B e Antigen -positive Chronic Hepatitis B: A Real-world Experience

PurposeThe loss of serum hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) is considered an ideal clinical outcome but rarely achieved with current standard of care. We evaluated the effectiveness in inducing HBsAg seroclearance in a real-world clinical cohort of Chinese patients with CHB treated with a combination of pegylated interferon (Peg-IFN) with tenofovir disoproxil fumarate (TDF) or monotherapy with each agent.MethodsA total of 330 patients with CHB were assigned to receive Peg-IFN plus TDF for 48 weeks (Peg-IFN plus TDF group), Peg-IFN alone for 48 weeks (Peg-IFN group), or TDF alone for 144 weeks (TDF group). The primary end point was the percentages of patients who achieved HBsAg seroclearance at week 72. Differences from the baseline characteristics and treatment data were compared using the χ² test for categorical variables or 1-way ANOVA for continuous variables. A Kaplan–Meier test was performed to compare the HBsAg loss among the 3 groups. Discrimination of responders versus nonresponders was quantified using AUC curves. Optimal cut-offs were selected based on Youden's J statistic defined as J = sensitivity + specificity-1.FindingsAt week 72, the Kaplan–Meier cumulative HBsAg loss was 11.5% in the Peg-IFN plus TDF group, 5.7% in the Peg-IFN group, and 0% in the TDF group. The percentage of patients with HBsAg loss was comparable in the Peg-IFN plus TDF and Peg-IFN groups (P = 0.143), but both were significantly higher than that in the TDF group (P = 0.000 and P = 0.010). In addition, a significantly higher percentage of patients in the combination group and Peg-IFN group had serum HBsAg of <100 IU/mL compared with the TDF group (32.7% vs 23.6% vs 9.2%; P < 0.001) but no significant differences in the percentages of patients with HBsAg <1000 IU/mL, the undetectable serum HBV DNA and hepatitis B e antigen seroconversion. Our model predicted serum HBsAg loss at week 72 (AUC = 0.846) if the HBsAg level was reduced by > 1.5 log₁₀ IU/mL from baseline at treatment week 24, an optimal timepoint for prediction of HBsAg loss in this cohort.ImplicationsA 48-week course of Peg-IFN and TDF combination therapy led to profound reduction in serum HBsAg level, resulting in a significantly higher rate of HBsAg loss compared with TDF monotherapy. Patients with steep HBsAg decline >1.5 log₁₀ IU/mL at week 24 well signaled a higher probability of achieving HBsAg loss at week 72.     

Hepatitis B core antibody screening of voluntary blood donors: an extended pilot study using a modified passive haemagglutination assay

Summary. Screening for hepatitis B surface antigen (HBsAg), even by the most sensitive techniques, fails to detect all carriers of the hepatitis B virus (HBV). The presence of hepatitis B core antibody (anti-HBc) in the absence of HBsAg is a common finding in donors implicated in cases of post-transfusion hepatitis B (PTHB), and viral DNA may also be demonstrated in many of these individuals. An extended pilot study of routine screening of all donations for anti-HBc in addition to HBsAg was introduced into the Mersey and North Wales Regional Transfusion Service in November 1991 to improve surveillance for carriers of HBV. In order to reduce costs a modified passive haemagglutination assay was evaluated and found to have a sensitivity of 99% and specificity of 98% compared with a conventional assay. In the first 6 months 60 530 donations were tested and 12 (0–02%) were found to have anti-HBc in the absence of HBsAg or adequate antibodies to HBsAg (anti-HBs). These sera will later be submitted for polymerase chain reaction (PCR) testing in order to determine their infectivity or otherwise by the detection HBV DNA sequences.     

Evaluation and management of hepatitis B virus infection in hematopoietic stem cell transplantation: before and after transplantation

HBV infection remains a major global health problem and continues to be a common cause of liver-related morbidity and mortality in both immunocompetent and immunosuppressed individuals. Reactivation of HBV is a serious complication of chemotherapy/immunosuppressive therapy in patients with HBV infection. In this article, we aim to describe the diagnosis, prevention and management of HBV infection in allogeneic hematopoietic stem cell transplant candidates, from the pre- to post-transplant period. The data currently available suggest that all individuals with hemato-/onco-logical malignancies who undergo chemotherapy/immunosuppressive therapy should be screened for hepatotropic viruses such as HBV and HCV. HBV surface antigen-positive individuals who receive chemotherapy/immunosuppressive therapy are at considerable risk of HBV reactivation. Antiviral prophylaxis prevents HBV reactivation, decreases reactivation-related morbidity and mortality, and prevents interruptions in chemotherapy/immunosuppressive therapy in such individuals. The optimal duration of antiviral prophylaxis remains to be elucidated. The vaccination of HBV-naive recipients and their donors against HBV infection prior to transplantation plays an important role in preventing acquired HBV infection. The presence of hepatitis B surface antigen positivity is not an absolute contraindication for allogeneic hematopoietic stem cell transplantation.     

男性吸毒人群既往医疗史与HBV感染状况调查

目的 了解男性吸毒人群中既往医疗史与乙型肝炎病毒感染状况.方法 随机抽取长沙市某戒毒所戒毒的452例男性毒瘾者,问卷调查既往病史及日常生活接触史,ELISA法检测HBV感染标志物及肝功能.结果 样本人群中是否有其他病毒性肝炎史与HBV总感染、HBsAg感染、大三阳、小三阳的感染率均有统计学关联.吸毒人员是否接受过血液制品与HBsAg感染率有统计学意义;吸毒者是否扎过耳环孔与HBsAg感染、小三阳率有关.结论 男性吸毒人员有其他病毒性肝炎史、其他医疗史等是HBV感染的非常重要的影响因素.     

中国治疗慢性乙型肝炎的成本-效果的系统评价

目的本研究旨在对中国现有慢性乙型肝炎干预措施的经济学分析研究进行系统评价.方法计算机检索MEDLINE和中国国内4个最大的电子数据库;同时筛检了纳入研究的参考文献,纳入所有慢性乙型肝炎干预措施的经济学评价研究.使用一个由25项组成的总量表评价纳入文献的质量.质量评价和资料提取由两名评价员独立进行.结果纳入19个完整的经济学评价和成本研究,其中14个研究的总体质量为22～44 分,7个研究为45～61分.大多数研究充分描述了干预措施的临床效果,但仅50%的研究充分报道了成本鉴定、测量和赋值三个过程.部分研究的数据分析存在问题,特别是敏感性分析和贴现两个方面.10个研究比较了拉米夫定、干扰素和常规治疗1年(或6个月)的效果,结果显示拉米夫定总体上成本-效果更好.3个研究比较了干扰素和常规治疗的长期效果(30年),干扰素治疗方案相对于常规治疗可节约成本,提高疗效.另3个研究比较了干扰素与其他不常用的抗病毒药物,结果其成本-效果不同.2项成本研究结果显示,随着疾病严重程度加剧,医疗成本占总成本比例和总成本均增加.结论在现有干预措施中,拉米夫定的短期成本-效果相对较好.干扰素的长期成本-效果相对常规治疗更好.但各干预措施的长期成本-效果尚不能根据现有研究得到可靠证实.此外,方法学质量,特别是成本的测算较低影响了研究结果的可靠性,有必要提高原始研究报告的质量.总之,运用现有结果进行决策时需仔细考虑.