Hepatitis B e antigen positive mother hepatitis B e antigen long persistence in her non-infected baby

We report the case of a baby born to a hepatitis B virus (HBV) carrier mother. This infant had a hepatitis B e antigen (HBeAg) in the serum until 6 months of age. Serial sera samples were analysed for HBV markers. No breakthrough of HBV infection was detected. The origin of this HBV marker has been questioned. Conclusion: HBeAg can persist at a non-infected baby born to an HBeAg-positive mother up to the age of 6 months.     

Factors associated with immunoprophylaxis failure against vertical transmission of hepatitis B virus

In spite of adequate immunoprophylaxis, perinatal transmission of hepatitis B virus (HBV) has not been completely eliminated. This study evaluated the factors associated with the failure of HBV immunoprophylaxis. The study participants were 144 children who were born to HBsAg-seropositive mothers of known HBeAg status and they had received HB immune globulin and HB vaccine within 24 hours after birth followed by two further administrations of HB vaccine as recommended. Seventeen of the children (11.8%) suffered immunoprophylaxis failure, defined by HBsAg-seropositivity. The rate of HBV immunoprophylaxis failure was 12%, 0%, 21%, 0%, and 27% among the children born to HBsAg-seropositive, HBeAg-seronegative, HBeAg-seropositive, undetectable HBV DNA, and detectable HBV DNA mothers, respectively. The failure of HBV immunoprophylaxis was significantly associated with maternal HBeAg-seropositivity and HBV DNA seropositivity. To identify those children at high risk of HBV immunoprophylaxis failure, maternal HBeAg and HBV DNA need to be assessed prior to childbirth.     

乙肝免疫球蛋白联合乙肝疫苗阻断乙型肝炎病毒母婴传播长期随访研究

目的研究乙肝免疫球蛋白(HBIG)联合乙肝疫苗阻断乙型肝炎病毒(HBV)母婴传播的长期效果。方法624例乙型肝炎病毒表面抗原(HBsAg)携带者母亲的婴儿随机分组,按0、1、6月龄单用乙肝疫苗20μg或出生时注射HBIG100IU,然后于1、2、7月龄接种乙肝疫苗20μg。静脉采血随访HBsAg,平均(6.34±1.71)年。结果同单用疫苗比较,HBIG联合免疫使1岁时慢性HBV感染率由17.6%降为5.0%;总慢性HBV感染率双阳性组由24.5%降至10.6%(P<0.005),单阳性组由10.7%降至3.8%(P<0.025)。双阳性组初现HBsAg阳性婴儿慢性化率也降低,在出生时HBsAg阴性而1～6个月时出现HBsAg阳性婴儿,慢性化率由40.9%降至0(P＜0.05),出生时HBsAg阳性婴儿1月龄HBsAg阴转率由26.4%提高至58.8%(P<0.05)。结论HBIG联合乙肝疫苗明显提高母婴传播阻断效果,减少慢性HBV感染率。其机理之一是减少初现HBsAg阳性婴儿的慢性化。     

乙型肝炎病毒相关性肾炎患儿的肝脏病变

目的：乙型肝炎病毒相关性肾炎(HBVGN)是我国常见的继发性肾小球疾病之一,以往人们只关心HBVGN时肾脏病变的问题,对无明显肝脏临床症状的“病毒携带者”或轻微的临床患者的肝脏的情况没有引起注意。该文探讨HBVGN时肝脏的病理变化。方法：选择13例HBVGN患儿同时进行肝肾病理活检。结果：13例患儿均有肝组织不同程度的受累,主要以轻度肝脏病理改变为主(9/13,占69.2%),HBV抗原在肝组织中主要以HBsAg检出率为高(10/13例,占76.9%);肾病理改变以膜性肾病为主(9/13,占69.2%),其次为系膜增生性肾炎(4/13例,占30.8%),HBV抗原在肾组织HBsAg和HBcAg的检出率均达100%,几乎所有的肾小管间质中有HBV抗原成分的分布。肝组织与肾组织中同时出现HBcAg的有4例。结论：HBVGN患儿均有不同程度的肝损害,而肾及肝组织病理改变不一定呈平行关系,肝组织与肾组织中同时出现HBcAg时肝肾同时损害均较重。提示对于HBVGN患者要重视肝肾同治。     

The development of hepatocellular carcinoma among prospectively followed children with chronic hepatitis B virus infection

We prospectively followed 426 children with chronic hepatitis B virus infection. During 6250 person-years, 2 boys developed hepatocellular carcinoma, with an incidence of 32 per 100,000 person-years. Both had e antigen seroconversion in early childhood and cirrhosis. Early e antigen seroconversion and/or cirrhosis may be risk factors for hepatocellular carcinoma.     

HLA typing associated with hepatitis B E antigen seroconversion in children with chronic hepatitis B virus infection: a long-term prospective sibling cohort study in Taiwan

OBJECTIVE: To conduct a prospective cohort study to clarify the relationship between human leukocyte antigen (HLA) polymorphisms and the seroconversion of hepatitis B e antigen (HBeAg). STUDY DESIGN: In the prospective cohort study, 81 HBeAg-positive children with chronic hepatitis B virus (HBV) infection from 40 unrelated families were recruited and followed-up regularly for a mean period of 17.70 +/- 3.23 years. The association between HLA antigen and the age at HBeAg seroconversion was analyzed using Cox regression model with shared frailties under left truncation and right censorship. RESULTS: HLA-B61 and HLA-DQB1*0503 antigens predicted a higher HBeAg seroconversion rate (relative incidence = 6.17 and 3.22, P = .024 and .017, respectively). Within-family frailty in our sibling cohort study demonstrated a negligible or a low degree of within-family correlation with spontaneous HBeAg seroconversion in each HLA antigen. CONCLUSIONS: HLA class I antigen B61 and class II antigen DQB1*0503 are associated with earlier HBeAg seroconversion in Taiwanese children with chronic HBV infection.     

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.     

乙型肝炎病毒相关性肾炎患儿乙型肝炎病毒S基因突变分析

目的 探讨乙型肝炎病毒(HBV)S基因的突变在乙型肝炎病毒相关性肾炎(HBV-GN)发病中的意义.方法 从53例患儿(30例HBV-GN,5例肾病伴HBV携带者,18例HBV携带者)的血清中提取DNA,以聚合酶链反应技术对HBV-DNA的S基因进行扩增,然后对扩增产物进行测序.结果 (1)S3例患儿血清型中52例为adw,在HBV携带组中1例为adr.(2)HBV基因型分型:30例HBV-GN中29例为B型,1例为E型;5例肾病HBV携带患儿为B型;18例HBV携带患儿中17例为B型,1例为C型.(3)30例HBV-GN中21例(70%)有点突变,共计17种突变,11种为错义突变,6种同义突变.16例(16/21,76.2%)点突变导致S抗原中氨基酸取代,其中11例(11/16,68.8%)涉及丝氨酸、苏氨酸、酪氨酸等潜在促分裂素原活化蛋白激酶(MAPK)和蛋白酪氨酸激酶(PTK)的磷酸化位点.5例肾病伴HBV携带者中2例有同义突变,3例无任何突变;18例HBV携带者共有3例同义突变,无氨基酸改变.结论 HBV-GN患儿大多存在HBV S基因变异并导致S抗原中氨基酸取代,其中主要涉及丝氨酸、苏氨酸、酪氨酸等MAPK和PTK的磷酸化位点,这些重要位点氨基酸的取代可能在HBV-GN的发病中起作用.     

乙型肝炎病毒母婴传播影响因素探讨

目的：探讨乙型肝炎病毒(HBV)母婴传播的影响因素,寻求降低婴儿HBV感染率的方法。方法：HBV携带及慢性乙型肝炎孕妇共635例,分别比较不同血HBV DNA滴度,不同分娩方式（剖宫产或自然分娩）,以及不同肝功能状态孕妇所生婴儿出生时及3月龄时HBV的感染率。新生儿生后12 h内肌注乙肝免疫球蛋白200 U 及重组酵母乙肝疫苗10 μg;生后即刻显示血清HBV感染存在者,14 d时再肌注乙肝免疫球蛋白200 U。结果：孕妇高滴度组（HBV DNA>105拷贝/mL）所生新生儿出生时（14.4% vs 4.1%,P<0.01）与3月龄时（4.7% vs 0,P<0.01）HBV感染率均高于低滴度组（HBV DNA ≤105拷贝/mL）。两组新生儿3月龄时HBV感染率均低于出生时（P<0.05）。自然分娩的孕妇其婴儿出生时HBV感染率明显高于剖宫产组（P<0.01）,但3月龄时,两组感染率接近。HBV携带孕妇所生婴儿出生时HBV感染率明显高于慢性乙型肝炎孕妇所生婴儿（P<0.01）,但3月龄时两组婴儿HBV感染率亦接近。结论：孕妇血清HBV DNA水平与新生儿HBV宫内感染密切相关,故降低孕妇血清HBV DNA水平可能成为减少新生儿HBV感染的一种有效途径。在乙肝免疫球蛋白及重组酵母乙肝疫苗的双重保护下,孕妇的分娩方式与肝功能状态对HBV母婴传播无影响。     

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.     

α干扰素治疗HBeAg阳性慢性乙型肝炎疗效的荟萃分析

目的评价α干扰素治疗HBeAg阳性慢性乙肝病毒感染儿童的长期疗效及安全性。方法检索PubMed和CHKD期刊全文数据库,并追查所有纳入研究的参考文献,进行荟萃分析。纳入用英文或中文发表的比较α干扰素与非抗病毒药物（安慰剂或空白对照）治疗HBeAg阳性慢性乙肝病毒感染儿童的随机对照试验。结果共纳入10个随机对照试验,包括542个HBsAg和HBeAg阳性的慢性乙型肝炎患儿。结果显示,随访6个月～2年,α干扰素组HBeAg转阴率高于对照组[31．1％vs12．4％,OR3．17,95％CI（2．00,5．02）,P〈0．00001],HBV—DNA转阴率高于对照组[33．9％vs16．2％,OR2．59,95％CI（1．70,3．96）,P〈0．0001],HBsAg转阴率高于对照组[5．5％vs1．2％,OR3．44,95％CI（1．20,9．89）,P=0．02],丙氨酸氢基转移酶（ALT）复常率高于对照组[43．0％vs27．7％,OR1．99,95％CI（1．16,3．42）,P=0．01],HBeAg血清学转换率高于对照组[30．4％vs12．8％,OR2．90,95％CI（1．56,5．39）,P=0．0008],两组差异均有统计学意义,但HBsAg血清学转换率与对照组相比[1．9％vs0,95％CI（0．42,18．13）,P=0．29],差异无统计学意义。结论对HBeAg阳性的慢性乙肝病毒感染患儿,α干扰素可能有使HBeAg转阴、HBV-DNA转阴、HBsAg转阴、ALT复常及HBeAg血清学转换的效应,但未能实现HBsAg血清学转换。受原研究质量和不同研究干预措施差异的影响,α干扰素的效应尚需更多高质量足够样本量的随机对照试验予以证实。     

检测尿HBV抗原诊断乙型肝炎相关性肾炎的价值

探讨检测尿乙型肝炎病毒（ＨＢＶ）抗原诊断乙型肝炎相关性肾炎的价值。肾小球病伴尿ＨＢＶ抗原阳性者可临床诊断乙肝肾炎。     

乙型肝炎高危儿免疫预防效果及乙肝病毒母婴传播影响因素分析

目的 分析乙型肝炎病毒(HBV)母婴传播影响因素及乙肝高危儿免疫预防的效果,为儿童乙肝防治提供科学依据。方法 回顾性调查539例HBsAg阳性产妇及其6个月至5岁的乙肝高危儿551例,并检测乙肝高危儿的乙肝标志物,分析乙肝病毒母婴传播的影响因素。结果 乙肝疫苗接种率为100%,96.6%联合注射了乙肝疫苗和乙肝免疫球蛋白(HBIG)。各年龄段乙肝高危儿的HBsAg阳性率差异无统计学意义;HBsAb阳性率随年龄增长逐步下降 (P<0.01)。高危儿母亲为HBsAg、HBeAg双阳性者较单纯HBsAg阳性的乙肝感染率高 (15.1% vs 0.2%,P<0.01)。单纯接种乙肝疫苗的高危儿乙肝感染率 (28.6%)高于联合免疫注射者 (2.8%),P<0.01。结论 乙肝高危儿HBsAb阳性率随年龄增高逐渐下降。母亲HBsAg、HBeAg双阳性和出生未联合免疫注射是乙肝病毒母婴传播的危险因素。     

IL-19基因多态性与儿童乙型肝炎病毒易感性研究

目的 探讨白介素19（IL-19）基因的单核苷酸多态性（SNP）与儿童乙型肝炎病毒（HBV）易感性的关系。方法 采用病例对照研究,收集HBsAg阳性儿童136例（病例组）,HBsAg阴性的健康儿童297例（对照组）,应用PCR 聚合酶链反应和DNA测序法进行基因分型。结果 IL-19基因的rs1798位点的基因型在病例组和对照组人群中频率分布差异有统计学意义,病例组的CG 基因型的比例显著高于对照组（P < 0.05）;IL-19基因的rs2243191位点的基因型和等位基因在HBV感染高危儿童感染组和未感染组人群中频率分布差异有统计学意义,感染组TC、CC基因型以及C等位基因的比例显著高于未感染组（P < 0.05）。结论 IL-19 基因SNP 位点rs1798的基因多态性可能与儿童乙型肝炎易感性相关;rs2243191的基因多态性可能与HBV感染高危儿童突破感染易感性相关。     

HBsAg阳性母亲的婴儿接种乙肝疫苗后慢性HBV感染相关因素探讨

为探讨HBsAg阳性母亲的婴儿接种乙肝疫苗后慢性HBV感染相关因素及机制,对624名儿童随访了(6.34±1.71)年。结果发现慢性HBV感染89例,其中82.0％始于6月龄前。HBeAg同时阳性母亲的婴儿慢性HBV感染率高于单阳性母亲的婴儿(单用疫苗,P<0.005;HBIG+疫苗,P<0.05),且在6月龄内出现HBsAg阳性时,慢性化率也高(单用疫苗,P<0.025)。联合使用HBIG和疫苗可进一步减少慢性HBV感染率(单阳性组,P<0.025,双阳性组,P<0.005)及在1月～6月HBsAg阳性婴儿慢性化率(双阳性组,P<0.025)。提示HBsAg阳性母亲的婴儿接种乙肝疫苗后慢性HBV感染主要发生于宫内或产程中。双阳性母亲的婴儿更易形成慢性HBV感染,HBIG联合疫苗的预防效果优于单用疫苗。     

Hepatitis B precore mutant in children with chronic hepatitis B virus infection

BACKGROUND: In adults, hepatitis B virus (HBV) with a G to A point mutation at nucleotide 83 in the precore region (mutant HBV 83), is commonly found in HB e antibody positive HBV carriers. It has been reported that this mutant is not able to produce HB e antigen. The exact prevalence of mutant HBV 83 in patients with chronic HBV infection is not fully understood, especially in children. METHODS: To investigate the role of mutant HBV 83 in children with chronic HBV infection, sera were tested for the presence of mutant HBV 83 using a mutation site-specific assay. RESULTS: Mutant HBV 83 was detected in 15 of 22 children (68%). Seven children were followed longitudinally, of which three were asymptomatic carriers and the other four had chronic hepatitis B on entry. There was no clear relationship between the disease activity and the presence of mutant HBV 83. CONCLUSIONS: It was concluded that mutant HBV 83 is commonly present in children with chronic HBV infection and this mutant is not necessarily associated with activation of hepatitis.     

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目的了解儿童乙型肝炎病毒(HBV)基因型与临床分度的关系。方法选择甘肃省人民医院儿科和兰州大学第一医院感染科2008年4月至2010年4月门诊和住院患儿中HBV-DNA阳性的124例乙型肝炎患儿,其中男84例,女40例。HBV携带者65例,慢性乙型肝炎59例(轻度31例、中度18例、重度10例),对以上患儿进行基因分型、同时检测肝功、术前出凝血、HBV-DNA载量。结果 124例肝病患儿中,C基因型62例(50.0%),B基因型48例(38.7%),B/C混合型9例(7.3%),非B/C型5例(4.0%);HBV携带者和轻度组中,以B基因型为主,分别为47.7%和45.2%;中度和重度组中,以C基因型为主,分别为72.2%和80%;在C、B基因型分布方面,HBV携带者和轻度组与中度和重度组比较差异有统计学意义;C基因型患者的HBV-DNA载量、丙氨酸转氨酶(ALT)、天冬氨酸转移酶(AST)、总胆红素(TBIL)均高于B基因型;C基因型患者与B基因型比较,凝血酶原时间(PT)延长、凝血酶原活动度(PTA)下降、纤维蛋白原(FIB)减少。B、C型通过母婴传播的比例差异无统计学意义。结论甘肃省儿童乙型肝炎病毒基因...     

国产及进口乙型肝炎免疫球蛋白阻断乙型肝炎病毒母婴垂直传播效果的研究

目的：探讨国产及进口乙型肝炎免疫球蛋白（HBIG）阻断HBeAg/或抗HBe（＋）、HBV－DNA定量PCR（＋）孕妇所生的新生儿宫内乙型肝炎病毒感染的效果。方法：于孕期第6个月起每月给予孕妇进口或国产HBIG2000IU肌注1次，预产期前5－7d再加强注射1次，新生儿娩出后3h内及第15天各肌注1次HBIG，以后按1、2、7、13个月注射基因工程乙肝疫苗10μg。结果：生后13个月时小儿HBsAg阳性率：国产HBIG组、进口HBIG Bayer组与Berna组分别为2．7％、2．2％、2．8％；抗－HBs阳性率分别为94．7％、95．6％、97．2％。13个月龄儿国产HBIG组3例、Bayer组和Berna组各1例检获HBsAg( )，乙型肝炎病毒母婴传播阻断率分别为96．9％、97．4％、96．7％。结论：国产HBIG阻断HBeAg( )孕妇新生儿宫内感染与进口HBIG一样有效，且国产HBIG安全、价廉。     

儿童乙型肝炎病毒基本核心启动子变异的检测及其意义

目的　探讨儿童慢性乙肝病毒基本核心启动子 (BCP)基因双变异 (nt176 2A→T和nt176 4G→A)的临床特征和意义。方法　采集空腹肘静脉血 ,分离血清备检 ;以金标层析方法检测乙肝病毒 (HBV)免疫标志物 ,以微板核酸探针杂交技术检测HBVBCP区双位点变异及其DNA定性 ;将研究对象分为轻、中、重 3组 ,分别统计各组BCP双变异阳性率 ,分析BCP区双变异与血清HBeAg的相关性。结果　慢性乙肝患儿HBVDNA检测阳性率82 98% (78/ 94 ) ,HBeAg阳性组显著高于阴性组 (P <0 0 0 1) ;BCP区双变异阳性率为 15 96 % (15 / 94 ) ,HBeAg阳性组明显低于阴性组 (χ2 =5 36 ,P <0 0 5 ) ;轻、中、重 3组HBVBCP变异率分别为 4 4 4 %、13 79%和 4 5 0 0 % ,中、重两组比较差异有显著性 (χ2 =5 91,P <0 0 5 )。结论　儿童慢性乙肝病毒BCP双变异检出率血清HBeAg阴性组明显高于HBeAg阳性组 ,此处双变异减少了但未完全终止HBeAg的产生 ;儿童慢性乙肝HBVBCP双变异发生率与病变程度呈正相关 ,检测BCP区双变异对病情预后的判断有一定参考价值。     

GM-CSF联合乙肝疫苗治疗宫内HBV感染慢性携带儿童的研究

目的 初步观察重组粒细胞－巨噬细胞集落刺激因子（GM－CSF）或乙肝免疫球蛋白（HBIG）联合酵母重组乙型肝炎疫苗（rHBvac）对宫内感染呈慢性乙型肝炎病毒（HBV）携带儿童的治疗作用。方法 母亲为慢性HBV携带者，出生时乙肝表面抗原(HBsAg）阳性经乙型肝炎疫苗免疫仍发展为慢性HBV无症状携带儿童27名，随机分为两组。Ⅰ组：14名，使用GM－CSF50μg和rHBvac 10μg同一部位肌肉注射，每月1次，共4次。Ⅱ组：13名，HBIG 200IU和rHBvac10μg不同部位肌肉注射，每月1次，共4次。治疗结束后1个月复查HBV－DNA定量及其他HBV标记。结果 两组各有12名儿童完成研究，治疗前丙氮酸转氨酶异常Ⅰ组3例，Ⅱ组4例，治疗后各有2例恢复正常；治疗前乙型肝炎e抗原（HBeAg）阳性Ⅰ组9例，Ⅱ组10例，治疗后各1例发生HBeAg/抗－HBe血清转换。HBV－DNA定量，治疗后和治疗前相比，Ⅰ组有显著下降（符号铁和检验P＝0.023），Ⅱ组变化不明显，两组中无HBsAg转阴病例。结论 GM－CSF联合乙肝疫苗对乙肝疫苗免疫失败的慢性HBV携带儿童有一定治疗作用。