应用原位杂交和原位聚合酶链反应技术检测肾组织中乙型肝炎病毒DNA

为深入探讨乙型肝炎病毒（ＨＢＶ）相关性肾炎的发病机理，应用地高辛素标记ＨＢＶＤＮＡ探针原位杂交和直接原位聚合酶链反应（ＰＣＲ）技术，对５例血清ＨＢＶ标志物阳性、临床诊断为ＨＢＶ相关性肾炎患儿的肾活检石蜡包埋组织切片行ＨＢＶＤＮＡ检测，并采用免疫组化ＬＳＡＢ法做标本的ＨＢＶ表面抗原（ＨＢｓＡｇ）检测。结果显示５例中有４例标本原位杂交和直接原位ＰＣＲ检测均呈ＨＢＶＤＮＡ阳性，ＨＢＶＤＮＡ阳性颗粒弥漫沉积于肾小球毛细血管袢、系膜区、肾小管及肾间质，表现形式以浆核型、核型为主；此４例ＨＢｓＡｇ亦阳性，ＨＢｓＡｇ阳性颗粒的分布与ＨＢＶＤＮＡ基本一致。提示ＨＢＶ不仅可通过免疫介导引起肾脏损害，而且有可能直接侵犯肾脏导致肾脏病变。     

聚合酶链反应对抗—HBc阳性母亲宫内传播乙肝病毒的研究

应用聚合酶反应技术检测１９例抗－ＨＢｃ－阳性，ＨＢｓＡｇ阳性之母婴ＨＢＶＤＮＡ。结果显示，２／６ＨＢｃ阳性母亲１／６抗－ＨＢｃ阴性婴儿，１例抗ＨＢｃ，ＨＢｅＡｇ阳母亲的ＨＢＶＤＮＡ阳性。证实了抗－ＨＢｃ阳性，ＨＢｓＡｇ阴性母亲不仅体内存在ＨＢＶＤＮＡ，而且经过子宫内胎盘传播导致了婴儿的宫内感染，说明不仅ＨＢｓＡｇ阳性母亲，而且ＨＢｓＡｇ阴性但抗－ＨＢｃ阳性母亲同样可引起乙肝的宫内感染，对乙肝母婴传     

产前注射乙型肝炎免疫球蛋白预防乙型肝炎病毒宫内感染的临床研究

目的 减少新生儿宫内感染乙型肝炎病毒（ＨＢＶ）,探讨孕妇被动免疫预防ＨＢＶ宫内感染的作用。方法 将１４１例无症状ＨＢｓＡｇ（＋）孕妇随机分为两组,预防组６９例,自孕２８周起每月注射１次乙型肝炎免疫球蛋白（ＨＢＩＧ）,每次２００ ＩＵ;对照组７２例,不注射ＨＢＩＧ。在孕妇孕２８周、分娩前和新生儿出生时分别检测静脉血ＨＢｓＡｇ,ＨＢｅＡｇ和抗－ＨＢｓ,部分产妇检测乳汁ＨＢｓＡｇ,ＨＢｅＡｇ。结果 预防组新生儿血清ＨＢｓＡｇ检出率（５．８％）明显低于对照组（１６．７％）Ｐ＜０．０５;预防组新生儿抗－ＨＢｓ阳性率（３０．４％）显著高于对照组（９．７％）Ｐ＜０．０５;两组母亲乳汁ＨＢｓＡｇ检出率无显著差异。结论 产前多次肌注ＨＢＩＧ可减少携带ＨＢＶ母亲所生新生儿宫内受ＨＢＶ感染。     

表现为肾病综合征的乙型肝炎病毒相关性肾炎临床特点与诊断标准商榷

为总结本院４２例小儿乙型肝炎病毒相关肾炎（ＨＢＶ－ＧＮ）中表现为肾病综合征（ＢＶ＿ＮＳ）的临床特点,合并肝 受损情况并提出诊断标准意见。对４２例患儿活检的肾组织进行病理分型、免疫组化检测ＨＢＶ抗原及原位杂交法检测ＨＢＶＤＮＡ,结果：４２例占有６例血清ＨＢＶ感染标志阴性,其肾组织有５例病理类型为膜性肾炎及ＨＢＶ抗原阳性,６例ＨＢＶＤＮＡ均阳性,除外了继发性肾小球疾病,最终仍确诊为ＨＢＶ－ＮＳ。故认为     

HBeAg阳性母亲乳汁中乙肝病毒基因检测

为评估ＨＢｅＡｇ阳性携带者母亲乳汁是否在传染性，对５０例ＨＢｅＡｇ阳性携带者母亲（同时设１５例正常对照）采用ＥＬＩＳＡ测定血清和乳汁中ＨＢｓＡｇ、ＨＢｅＡｇ滴度，双用点印迹杂交（ＤＯ＋ｂｌｏｔ）、ＰＣＲ＋ＳＢＨ技术分别测定血清和乳汁中ＨＢＶＤＮＡ浓度。结果显示血清中ＨＢｓＡｇ、ＨＢｅＡｇ滴度高则初乳中滴度亦高（Ｐ〈０．０００１），但采用点印迹杂交技术测定血清和乳汁中ＨＢＶ－ＤＮＡ浓度，凡血清和乳汁     

407例新生儿抗—HCV调查

４０７例血清ＨＢｓＡｇ阳性母亲分娩的婴儿，于出生后２４－３６小时内用ＥＬＩＳＡ法检测其血清的抗－ＨＣＶ，阳性率为４．６７％（１９／４０７），其中１０５例母亲产前检测血清抗－ＨＣＶ，９例阳性，检出率为８．５７％。此９例抗－ＨＣＶ阳性的母亲所生婴儿有４例抗－ＨＣＶ阳性，而９６例抗ＨＣＶ阴民生的母亲所生婴儿只有３例抗－ＨＣＶ阳性，差异非常显著（ｘ＾２＝２２．５７，Ｐ〈０．００１），提示ＨＣＶ存在母婴生趣     

慢性乙型肝炎病毒携带者接种甲型肝炎疫苗

［英］／Ｎｅｂｂｉａ　Ｇ…／／ＪＰｅｄｉａｔｒ．－１９９９,１３６（６）．－７８４～７８５甲型肝炎（ＨＡ）预后通常良好,偶致暴发性肝功能衰竭．研究表明,慢性肝病者发生重度或暴发性ＨＡ的危险性增高．对３３例慢性乙型肝炎病毒感染患儿进行ＨＡ疫苗接种,以评价灭活ＨＡ疫苗的安全性及致免疫性．病人与方法３３例患儿中男２４例,女９例,中位年龄１０．７岁（２—１５岁）,血清抗ＨＡＶ均阴性,体健,均为慢性ＨＢｓＡｇ携带者,１８例ＨＢｅＡｇ阳性,１５例抗ＨＢｅ阳性,１３例血清丙氨酸氨基转移酶（ＡＬＴ）及天冬氨酸转…     

阿糖腺苷联合胸腺素治疗乙型肝炎病毒相关明炎的疗效观察

本探讨阿糖腺苷联合胸腺素治疗乙型肝炎病毒相关肾炎（ＨＢＶ－ＧＮ）的疗效。１７例临床表现为肾病综合征的ＨＢＶ－ＧＮ分为治疗组（７例）和对照组（１０例）,结果：治疗组完全缓解率（８５．７％）高于对照组（４０．０％）,尿蛋白转阴时间（２６±１４天）显短于对照且。本结果提示Ａｒａ－Ａ联合胸腺素治疗ＨＢＶ＿ＧＮ优于单纯皮质激素治疗。     

阻断乙型肝炎病毒宫内传播的初步研究

宫内已感染乙型肝炎病毒（ＨＢＶ）是新生儿接种乙肝疫苗免疫失败的主要原因。为了减少新生儿产前在宫内受ＨＢＶ感染，提高乙肝疫苗接种后的免疫效果，研究给予阻断措施和观察其效果。从３６３２名孕妇筛查出ＨＢＶ无症状携带者２０４例，随机分为二组，即临产前３个月每月注射１次乙型肝炎免疫球蛋白（ＨＢＩＧ），每次２００ＩＵ，和不注射者作对照。在孕妇分娩后和新生儿出生时分别抽外周血作血清学检测。结果显示，ＨＢＩＧ组和对照组所生新生儿的宫内感染率分别是５．７％和１４．７％（Ｘ￣２＝４．５８，Ｐ＜０．０５）。分娩后二组孕妇的ＨＢｓＡｇ和ＨＢｅＡｇ的阳性率无差异，但ＨＢＩＧ组ＨＢｓＡｇ阳性滴度的均值显著低于对照组（ｔ＝４．８２，Ｐ＜０．０１）。提示产前多次肌注ＨＢＩＧ可减少携带ＨＢＶ母亲所生新生儿宫内受ＨＢＶ感染。这可能与产时减少母体外周血中的ＨＢＶ有关。接受ＨＢＩＧ在分娩前后的随访无不良反应。     

乙型肝炎病毒宫内感染

乙肝病毒宫内感染是发展成乙肝表面抗原慢性携带者重要原因之一，也是导致生后接种乙肝疫苗失败的主要原因。国内外资料报告其宫内感染率高达１３％－４４％。我们对湖北省荆门市的孕妇乙肝病毒宫内感染进行调查，２７３名孕妇产前乙肝病毒感染标志表明：ＨＢｓＡｇ阳性率为９．９８％，抗－ＨＢｅ阳性率为４．３７％；抗－ＨＢｃ阳性率为５．６％，ＨＢｓＡｇ，ＨＢｅＡｇ双阳性者为６．６６％。     

Glomerulonephritis Associated With Hepatitis B Virus Infection in Children

Hepatitis B surface antigen (HBsAg) was identified by a reversed passive hemagglutination (RPHA) method in the serum of 13 of 15 patients with membranous glomerulonephritis (MGN), three of three Type III membranoproliferative GN (MPGN) proposed by Burkholder, three of 25 idiopathic minimal change nephrotic syndrome (IMCNS), three of 37 minor glomerular alterations with undetermined diagnosis (MGA) and none of 79 various other renal disease, in 266 Japanese children. Immunofluorescent studies showed granular deposition of Hepatitis B e antigen (HBeAg) in a similar pattern to that of IgG and β1C in the kidney of four patients with MGN, and of HBsAg in one with Type III MPGN. Eight of 13 MGN with positive serum HBsAg, two of three Type III MPGN and one of one MGA with positive serum HBs Ag had normalization of urinary findings during the observation period of one to eight years. Eight (5 MGN, 2 Type III MPGN and 1 MGA) of those with positive serum HBeAg showed seroconversion of HBeAg, and anti-HBe appeared in five of eight as the urinary findings became normal. The normalization of urinary findings accompanied by seroconversion of HBeAg in the patients with MGA and with Type III MPGN suggests that HBeAg is the most important antigen involved in HB virus (HBV) associated GN including not only MGN but also Type III MPGN and MGA.     

Study on Efficacy of Hepatitis B Immunization in Vaccinated Beta-thalassemia Children in Tehran

Objective

In thalassemic children, HBV infection is common, thus immunization against HBV will reduce and prevent the rate of infection. The aim of this study was to evaluate the efficacy of HBV immunization and the prevalence of HBV infection in beta-thalassemic children in Tehran.

Methods

To assess the efficacy of immunization and determine the immune response of children with beta-thalassemia, sera of 99 children who had received three doses (10/20 µg) of recombinant HBV vaccine in months 0, 1, 6, were selected and tested for HBsAg, HBsAb and anti-HBc by ELISA method. Also, these sera were tested for HBV DNA using nested-PCR method.

Findings

In 99 beta-thalassemic children, 89 (89.9 %) were anti-HBs positive (responders) and 10 (10.1%) anti-HBs negative (non-responders). 3 (3.03%) were anti-HBc positive and 1(1.01%) was HBsAg positive. HBV DNA was not detected in any of them.

Conclusion

Our results have revealed that hepatitis B vaccine is highly immunogenic for thalassemic children and particularly well tolerated.     

Hepatitis B virus infection

Hepatitis B virus (HBV) infection is a worldwide health problem and may cause acute, fulminant, chronic hepatitis, liver cirrhosis, or hepatocelullar carcinoma (HCC). Infection with HBV in infancy or early childhood may lead to a high rate of persistent infection (25-90%), while the rates are lower if infection occurs during adulthood (5-10%). In most endemic areas, infection occurs mainly during early childhood and mother-to-infant transmission accounts for approximately 50% of the chronic infection cases. Hepatitis B during pregnancy does not increase maternal mortality or morbidity or the risk of fetal complications. Approximately 90% of the infants of HBsAg carrier mothers with positive hepatitis B e-antigen (HBeAg) will become carriers if no immunoprophylaxis is given. Transplacental HBeAg may induce a specific non-responsiveness of helper T cells and HBcAg. Spontaneous HBeAg seroconversion to anti-HBe may develop with time but liver damage may occur during the process of the immune clearance of HBV and HBeAg. Mother-to-infant transmission of HBV from HBeAg negative but HBsAg positive mothers is the most important cause of acute or fulminant hepatitis B in infancy. Although antiviral agents are available to treat and avoid the complications of chronic hepatitis B, prevention of HBV infection is the best way for control. Screening for maternal HBsAg with/without HBeAg, followed by three to four doses of HBV vaccine in infancy and hepatitis B immunoglobulin (HBIG) within 24h of birth is the most effective way to prevent HBV infection. In areas with a low prevalence of HBV infection or with limited resources, omitting maternal screening but giving three doses of HBV vaccine universally in infancy can also produce good protective efficacy. The first universal HBV immunisation programme in the world was launched in Taiwan 22 years ago. HBV infection rates, chronicity rates, incidence of HCC and incidence of fulminant hepatitis in children have been effectively reduced.     

儿童异基因造血干细胞移植术后乙型肝炎病毒免疫标记的变化

目的 了解儿童异基因造血干细胞移植（allo-HSCT）前后乙型肝炎病毒（HBV）免疫标记的变化情况,探讨供受者allo-HSCT前不同HBV免疫状态与allo-HSCT后受者HBV免疫标记变化的关系.方法 回顾性分析2010年1月-2012年6月在我院接受allo-HSCT治疗的130例儿童血液病患儿移植前后HBV免疫标记物（HBsAg、HBsAb、HBeAg、HBeAb及HBcAb）、HBV-DNA等临床资料,移植后随访中位时间18（6 ～36）个月.结果 （1）allo-HSCT前：HBsAg阴性患儿126例,阳性4例;HBsAb阳性患儿92例;HBsAg阳性供者6例,余均为HBsAg阴性供者.（2）allo-HSCT后：16例移植前HBsAb阴性受者移植后转为HBsAb阳性：66例移植前HBsAb阳性受者接受HBsAb阳性供者移植后,47例仍为HBsAb阳性,18例为HBsAb阴性,1例发生HBV再激活;21例移植前HBsAb阳性受者接受HBsAb阴性供者移植后,13例转为HBsAb阴性.（3）移植前供者HBsAb阳性,输注CD34＋细胞＞7.24×106/kg、移植前受者HBsAb滴度高低对移植后受者HBsAb转为阴性有显著影响,P值分别为0.005、0.040和0.000.（4）2例移植前合并HBV感染患儿移植后发生HBV再激活,2例移植前无HBV感染患儿接受大三阳供者移植后继发HBV感染.结论 HBsAb阴性患儿接受HBsAb阳性供者allo-HSCT后,在造血和免疫功能重建的同时,其体内可产生针对HBV的保护性抗体;移植后受者HBsAb随时间逐渐丢失,丢失的比例与移植前受者HBsAb滴度高低、输注CD34＋细胞数高低、供者HBsAb阳性与否明显相关.因此,移植前对供受者进行针对HBV的免疫接种及移植后免疫重建后对受者再次免疫接种有利于预防移植后HBV激活及感染.     

儿童乙型肝炎病毒相关性肾炎临床病理分析

目的 探讨儿童乙型肝炎病毒相关性肾小球肾炎(HBV—GN)临床及病理特点。方法 分析35例HBV—GN的临床表现及肾活检光镜、免疫荧光和电镜特点。结果 35例HBV-GN临床表现以肾病综合征(NS)为主(32／35，91．4％)；肾小球肾炎3／35(8．6％)。病理类型以膜性肾病(MN)最多见(33／35，94．3％)；其次系膜增生性肾炎(MsPGN，2／35，5．7％)。免疫荧光检查呈多种免疫复合物沉积。电镜观察HBV—MN易见电子致密物系膜沉积，2例肾小球基底膜内观察到病毒样颗粒。结论 儿童HBV—GN临床常表现主要为NS，病理特征以Ⅲ为主，诊断不必强调HBsAg、HBcAg在肾组织上沉积，肾组织病理特点提示HBV可通过多种机制引起肾损害。     

National Project on the Prevention of Mother-to-Infant Infection by Hepatitis B Virus in Japan

In Japan, a nationwide prevention program against mother-to-infant infection by hepatitis B virus (HBV) started in 1985. This program consists of double screenings of pregnant women and prophylactic treatment to the infants born to both hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive mothers. These infants are treated with two injections of hepatitis B immune globulin (HBIG) and at least three injections of plasma derived hepatitis B vaccine. We sent questionnaires about the numbers of each procedure or examination during nine months of investigation period to each local government in 1986 and 1987. 93.4% pregnant women had the chance to be examined for HBsAg, and the positive rate was 1.4 to 1.5%. The HBeAg positive rate in HBsAg positive was 23 to 26%. The HBsAg positive rate in neonates and in infants before two months were 3% and 2% respectively. Some problems may arise, because 27 to 30% of infants need the fourth vaccination in some restricted areas.     

儿童血清学阴性乙型肝炎病毒相关性肾炎13例临床与病理分析

目的 回顾性分析儿童血清学阴性乙型肝炎病毒相关性肾炎（sn HBV-GN）的临床及病理学特征,并初步探讨免疫抑制剂治疗的安全性和有效性。方法 收集 2006 年 1 月至 2011年12月经首都医科大学附属北京儿童医院肾活检诊断为HBV-GN病例,根据血清学结果筛选出HBsAg和HBV-DNA阴性患儿,分析其临床、病理资料和治疗情况。结果 13例sn HBV-GN患儿进入分析,男8例,女5例,平均年龄11.8岁。临床表现以肾病综合征为主（11例）,9例伴有血尿;2例表现为肾炎综合征。①11例以不典型膜性肾病为主要病理表现,免疫荧光以IgG、C3沉积为主, 亦可见IgA、IgM、C1q沉积。②肾组织HBsAg与HBcAg阳性率分别为100%（13/13）和76.9%（10/13）,强阳性率分别为23.1%（3/13）和15.4%（2/13）。③2例肾炎综合征患儿经抗凝和卡托普利治疗完全缓解;11例肾病综合征患儿,单纯抗病毒治疗2例均未缓解;单纯糖皮质激素治疗2/3例部分缓解,糖皮质激素加环孢素治疗2/3例部分缓解,糖皮质激素加用麦考酚酸酯治疗3例均完全缓解。加用免疫抑制剂患儿均未发现肝功能异常及HBV-DNA活动表现。结论儿童sn HBV-GN的病理以不典型膜性肾病为主要表现;免疫荧光显示免疫复合物的种类少,沉积强度低;麦考酚酸酯联合激素治疗较单用激素或激素联合环孢素治疗可能有效,单纯抗病毒治疗可能无效。     

Hepatitis B virus infection and glomerulonephritis

Hepatitis B antigenemia has been associated and implicated in many glomerular diseases. One hundred and ten children with glomerulonephritis were taken up for the study. HBs Ag and Anti HBs were estimated. 52% of children were positive for HBV markers. Preceding jaundice, hypertension, hematuria were seen more in children with HBV markers. Children with acute nephritic syndrome recovered spontaneously. A higher relapse rate and steroid resistance were seen in nephrotics with HBV markers. Histologically, membranous nephropathy and membranoproliferative glomerulonephritis were seen mainly in children who were HBs positive.     

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??Objective To investigate the serological patterns of hepatitis B virus and the distribution characteristics among 0-7-year-old children. Methods The detection results of hepatitis B virus serological markers ??HBVM?? in 0-7-year-old children and the family history of ‘HBsAg??+??’ children from Children's Hospital of Chongqing Medical University in 2013 were analyzed retrospectively. Results Seventeen serological patterns of hepatitis B virus were found??and the detection rate of each pattern in different age groups was different. The positive rate of HBsAg was 0.32%??and there were no significant differences in HBsAg positive rate in different age groups. The detection rates of ‘anti-HBs??+?? anti-HBc??+??’??‘anti-HBs??+?? HBeAg??+?? anti-HBc??+??’??‘anti-HBs??+?? anti-HBe??+?? anti-HBc??+??’??‘anti-HBc??+??’ and ‘anti-HBe??+?? anti-HBc??+??’ in 0 to 28 day age group and 1 month to 1-year age group were significantly higher than other age groups ??P??0.05??. PreS1-Ag was detected in five serological patterns??the highest frequency pattern was ‘HBsAg??+?? HBeAg??+??’ ??100%???? followed by ‘HBsAg??+?? HBeAg??+?? anti-HBc??+??’. The detection rate of PreS1-Ag in the HBeAg ??+?? group was 80.77%??which was significantly higher than the HBeAg ??-?? group ??χ2??14.083??P??0.000??. Conclusion There is no significant change in positive rate of HBsAg with the increase of age among 0-7-year-old children in Chongqing??but the distribution of serological patterns is associated with age. There is correlation between PreS1-Ag and HBeAg??and the combined test of the two serological markers can better reflect the HBV replication??which has important clinical value.     

预防乙型肝炎病毒母婴传播的随机对照研究

目的探讨乙肝免疫球蛋白（HBIG）预防乙型肝炎病毒（HBV）母婴垂直传播的效果。方法以2001年1月至2005年5月在台州医院产科初次进行妊娠健康检查,HBsAg测定阳性或HBsAg、HBeAg均阳性孕妇作为研究对象,共279例。将单纯HBsAg阳性孕妇与HBsAg、HBeAg双阳性孕妇分别应用随机数表方法随机分组,分别为单阳注射组（n=80）、单阳对照组（n=60）、双阳注射组（n=79）、双阳对照组（n=60）。单阳注射组、双阳注射组于妊娠加周开始肌肉注射HBIG 200U,每4周注射1次,直至临产。两对照组不注射HBIG。4组孕妇所产婴儿,除常规接种乙肝疫苗外,均于出生后16h内和2周肌肉注射HBIG。然后随访并测定婴儿HBsAg。结果单阳注射组、单阳对照组、双阳注射组、双阳对照组所生婴儿HBsAg感染率分别为3％、13％、10％、32％。单阳注射组与单阳对照组之间（x^2=6．07,P〈0．05）,以及双阳注射组与双阳对照组之间婴儿HBsAg感染率（x^2=10．11,P〈0．01）均有统计学意义,注射HBIG组,对单纯HBsAg阳性孕妇及HBsAg、HBeAg双阳性孕妇,出生婴儿HBsAg感染率均显著低于对照组;单阳注射组与双阳注射组之间婴儿HBsAg感染率差异亦有统计学意义,说明HBIG对单纯HBsAg阳性孕妇预防效果优于HBsAg、HBeAg双阳性孕妇。结论HBIG能有效预防母婴传播,降低HBV感染率。因此,妊娠妇女应及时进行健康检查,发现HBV感染阳性,及时采取注射HBIG等有效措施,以促进优生优育。