α-干扰素联合糖皮质激素序贯治疗儿童慢性乙型肝炎疗效的Meta分析

目的评价α-干扰素(alpa interferon,IFN-α)联合糖皮质激素序贯治疗与α-干扰素单独治疗HBeAg阳性慢性乙型肝炎儿童的疗效差异。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。检索年限均从建库检索到2006年10月。纳入用英文或中文发表的比较IFN-α联合糖皮质激素序贯治疗与IFN-α单独治疗HBeAg阳性慢性乙型肝炎儿童疗效的随机对照试验。由2名评价员独立筛查文献,评价质量和提取资料。结果共纳入4个随机对照试验,包括181个HBeAg阳性的慢性乙型肝炎患儿。Meta分析结果显示,随访9个月至2年后,IFN-α联用糖皮质激素序贯组治疗HBeAg转阴率稍低于IFN-α单独治疗组,HBV-DNA转阴率稍高于IFN-α单独治疗组,HBsAg转阴率稍低于IFN-α单独治疗组,丙氨酸转氨酶(ALT)复常率稍低于IFN-α单独治疗组,HBeAg血清转换率稍低于IFN-α单独治疗组,HBsAg血清转换率稍高于IFN-α单独治疗组,两组差异均无统计学意义。结论对HBeAg阳性的慢性乙型肝炎患儿,IFN-α联用糖皮质激素序贯治疗与IFN-α单独治疗对比,在HBeAg转阴、HBV-DNA转阴、HBsAg转阴、ALT复常、HBeAg及HBsAg血清转换等方面均无明显的效能。     

临床路径应用于小儿支气管肺炎疗效的Meta分析

目的系统评价临床路径应用于小儿支气管肺炎的疗效。方法计算机检索PubMed、CochraneLibrary、Webof Knowledge、万方、维普中文科技期刊全文数据库、中国知网期刊全文数据库,所有数据库均检索至2014年3月。查找临床路径应用于d,JL支气管肺炎的随机对照试验,使用RevMan5．2软件进行Meta分析。结果最终纳入6个研究,患儿共24559例,临床路径组12269例,传统治疗组12290例。Meta分析结果显示,通过临床路径管理,不仅缩短了支气管肺炎患儿住院天数[MD=-1．21,95％CI（-1．95,-0．48）,P=0．001],而且还降低了住院总费用[SMD=-3．68,95％CI（-5．04,-2．32）,P〈0．0001],减少抗生素使用天数[MD=-1．20,95％CI（-1．51,-0．89）,P〈0．00001],进一步提高了患儿的治愈率[OR=1．67,95％CI（1．03,2．77）,P=0．04]和患者满意度[OR=6．12,95％C1（3．12,12．04）,P〈0．00001]。结论临床路径应用于d,JL支气管肺炎管理,效果明显优于传统治疗流程,具有可行性和实用价值。     

氧化苦参碱联合干扰素治疗儿童慢性乙型肝炎

目的研究氧化苦参碱联合干扰素治疗儿童慢性乙型肝炎的效果。方法84例慢性乙型肝炎患儿随机分为二组。治疗组采用氧化苦参碱联合干扰素α-2b治疗,对照组予干扰素α-2b,治疗3、6个月后观察肝功能、HBV DNA及HBeAg转阴率变化。结果治疗3和6个月二组临床症状、肝功能均明显改善,治疗组优于对照组（P〈0.05,0.01）;治疗6个月HBeAg和HBV DNA转阴率治疗组高于对照组（P〈0.05,0.01）。结论氧化苦参碱和干扰素联用在改善慢性乙型肝炎患儿肝功能及HBeAg和HBV DNA转阴率方面具有协同作用。     

川崎病Toll样受体MyD88非依赖性信号途径及其调节因子的研究

目的探讨Toll样受体MyD88非依赖性途径及其调节因子在川崎病（KD）免疫发病机制中的作用。方法急性期KD患儿32例,正常同年龄对照组16例,KD患儿分别于静脉丙种球蛋白（IVIG）治疗前后直接取血备检。采用逆转录-聚合酶链反应（RT-PCR）及荧光定量PCR（RealTimePCR）检测单核／巨噬细胞（MC）Toll样受体4及MyD88非依赖性途径传导分子／效应分子,如含Toll-白细胞介素-1受体结构域诱导干扰素接头分子（TRIF）、TRIF相关接头分子（TRAM）、TANK结合激酶1（TBK-1）、干扰素B（IFN-β）、干扰素诱导蛋白10（IP-10）、活化正常T细胞表达和分泌的调节因子（RANTES）、诱导性一氧化氮合成酶（iNOS）等,及负性调节因子细胞因子信号抑制因子1（SOCS-1）mRNA表达;流式细胞术检测MC细胞表面共刺激分子CIM0的表达;甲基化特异性-荧光定量PCR分析SOCS．1基因胞嘧啶鸟嘌呤二核苷酸（CpG）基序甲基化状态。结果（1）急性期KD患儿MCMyD88非依赖性途径传导分子TLR4、TRIF、TRAM、TBK-1和IFN-BmRNA表达水平显著高于正常同年龄对照组（P〈0．05）;（2）趋化因子IP-10、RANTES和iNOSmRNA表达水平明显增加（P〈0．05）;（3）急性期KD患儿MC细胞表面共刺激分子CD40明显高于同年龄对照组[（6．19±2．25）％vs．（2．00±1．37）％,t=7．98,P〈0．05],合并冠状动脉组（KD-CAL^＋）CD40表达明显高于无冠状动脉组[KD-CAL^-,（9．63±2．96）％vs．（4．12±1．91）％,t=16．02,P〈0．05];（4）急性期KD患儿MC细胞SOCS-1 mRNA水平显著高于同年龄对照组[（4．31±0．83）×10^-3vs．（1．09±O．23）×10^-3,t=20．43,P〈0．05],KD-CAL^＋组SOCS-1 mRNA表达明显低于KD-CAL^-组[（5．73±1．04）×10^-3vs．（1．94±0．46）×10^-3,t=14．15,P〈0．05];（5）KD患儿急性期SOCS-1基因CpG序列去甲基化水平明显增高[（26．9±8．6）％vs．（5．9±1.4）％,t=13．46,P〈0．05],KD-CAL^＋组SOCS-1基因去甲基化水平显著低于KD-CAL^-组[（35．1±10．3）％vs．（13．2±3．7）％,t=8．63,P〈0．05]。结论急性期KD患儿MyD88非依赖性途径异常活化可能是导致KD免疫功能紊乱的因素之一。     

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。     

重组干扰素α-1b治疗慢性乙型肝炎疗效观察

目的研究基因重组干扰素α-1b治疗慢性乙型肝炎(CHB)患儿的疗效及影响因素。方法将68例CHB患儿分为观察组36例,对照组32例。对照组予保肝药物治疗;观察组在此治疗基础上予重组干扰素α-1b治疗。并对两组疗效进行比较。结果观察组HBeAg、HBV-DNA转阴率明显高于对照组(P<0.01),而两组ALT复常率和HBsAg转阴率无明显差异(P>0.05);重组干扰素α-1b治疗CHB患儿疗效与ALT水平、HBV-DNA含量、年龄、性别有关。结论重组干扰素α-1b是治疗CHB的有效药物。     

彝族儿童幽门螺杆菌感染HLA-DQA1免疫遗传学特征分析

目的研究人类白细胞抗原(HLA)DQA1基因位点上是否存在H.pylori感染的易感基因或抵抗基因，探讨免疫遗传因素在H.pylori感染中的作用。方法用聚合酶链反应-序列特异性引物(PCR-SSP)技术对用血清学试验及^13C尿素呼气实验确诊的31例H．pylori感染的彝族儿童及39例无感染儿童进行HLA．DQA1基因分型。结果感染组HLA-DQA1*0102等位基因频率明显高于对照组(14．52％vs3．85％，P=0．025，Pc=0．35)，OR=4．245(95％CI：1．097～16．428)；感染组HLA-DQA1*0302等位基因频率低于对照组(0 vs12．82％，P=0．003，Pc=0．042)，OR=1．147(95％CI：1．053-1．249)。结论在HLA-DQA1位点上，H．pflori感染的彝族儿童与对照组儿童存在免疫遗传学差异，HLA-DQA1*0102基因可能是彝族H．pylori感染的易感基因，而HLA-DQA1*0302基因则可能是抵抗基因和具有免疫抵抗作用。     

1型糖尿病患儿血清干扰素γ诱导蛋白10水平的变化及其意义

目的观察趋化因子干扰素γ诱导蛋白10（IP-10）在儿童1型糖尿病（T1DM）发病中的变化。方法用ELISA法检测50例T1DM患儿和30例健康儿童的血清IP-10水平,根据自身抗体存在与否、自身抗体阳性种类数及不同病程对IP-10进行分组比较。结果T1DM患儿血清IP-10水平[（367±131）ng／L]显著高于对照组[（133±43）ng／L],差异有统计学意义（t=9．49,P〈0．01）。其中自身抗体阳性组IP-10[（385±147）ng／L]和自身抗体阴性组IP-10[（311±101）ng／L]均高于对照组（t=8．99,P〈0．01;t=8．67,P〈0．01）,但该两组间差异无统计学意义。1种、2种和3种自身抗体阳性患儿血清IP-10水平差异无统计学意义（F=1．46,P〉0．05）。初发组和病程〉12年组的T1DM患儿血清IP-10均高于对照组（t=10．34,P〈0．01;t=4．36,P〈0．01）,而病程〉12年组血清IP-10水平低于初发组（t=4．30,P〈0．01）。结论T1DM患儿血清IP-10水平高于对照组,血清IP-10水平不受自身抗体阳性存在与否、自身抗体阳性种类多少的影响,随病程延长,血清IP-10水平逐渐下降。     

中国儿童哮喘患病率的地区差异与生活方式的不同有关

目的通过对环境因素及生活方式的比较研究,探讨导致中国不同地区儿童人群中哮喘患病率差异的原因。方法对10902名来自北京、广州、香港三城市的儿童进行横断面研究,按照国际儿童哮喘和过敏性疾病研究（ISAAC）第二阶段方案,由儿童家长或监护人完成问卷调查,并随机抽取3479名儿童进行吸人性过敏原的皮肤点刺试验,对哮喘、特应性与环境和生活方式危险因素的相关性进行Logistic回归分析。结果过去12个月喘息的现患率分别为：香港5．8％,北京3．8％,广州3．4％,香港显著高于中国大陆（OR1．64,95％CI1．35—1．99）。多变量Logistic回归分析显示,应用煤气煮食（OR2．08,95％CI1．32—3．26）、海绵枕头（OR1．94,95％CI1．19—3．16）、房间潮湿（OR1．84,95％CI1．25—2．71）均是“近期喘息”的危险因素。而棉被的使用（OR0．70,95％CI0．56—0．87）、母乳喂养（OR0．79,95％CI 0．66—0．96）及参加日托（OR0．73,95％CI0．59—0．88）是“近期喘息”的保护性因素。结论具有中国大陆生活特征的环境因素及生活方式（母乳喂养、参加日托、使用棉被、使用非海绵的枕头、非煤气的煮食燃料、家中墙上或天花板没有潮湿霉点）是导致中国香港与大陆儿童哮喘患病率差异的重要影响因素。     

新生儿肠外营养相关胆汁淤积因素612例分析

目的为提高危重新生儿肠外营养支持的安全性和有效性提供依据。方法对1985．4—2005．3行5d以上静脉营养支持的612例住院新生儿资料进行分析。612例分为甲组（1985．4—1995．3）和乙组（1995．4—2005．3）。其中甲组70例再分为肠外营养相关胆汁淤积组（PNAC组）6例和非PNAC组64例,乙组542例也分为PNAC组12例和非PNAC组530例。比较甲乙两组新生儿PNAC发生率及相关因素。结果接受5d以上静脉营养支持的新生儿PNAC总发生率为2．94％,甲组PNAC发生率为8．57％,乙组发生率为2．21％,后10年PNAC发病率有明显下降（OR值为0．242,95％CI为0．088～0．666）。PNAC组的胎龄、出生体重均小于非PNAC组（其中胎龄33±5周比（36±4）周,P=0．009;OR值为0．827,95％CI为0．698～0．980。出生体重2003g±743g比2393g±764g,P=0．045;OR值为1．001,95％CI为0．999～1．002）,而平均PN持续时间、热卡摄入量均大于非PNAC组（其中PN持续时间32d±30d比13d±10d,P=0．000;OR值为1．072,95％c,为1．032～1．112。PN摄入量（272±46）kJ／（kg·d）[（65．0±10．9kcal／（kg·d）,（1kcal=4．184kJ）]比（232±55）kJ／（kg·d）[（55．5±13．1）kcal／（kg·d）],P=0．002;OR值为1．066,95％CI为1．012～1．122）。非PNAC组体重增加与PNAC组相比有增加趋势[（20±27）g／d比（9±19）g／d,P=0．175]。结论PNAC发生与早产、低出生体重、PN持续时间超过2周、PN提供的热卡量过高有关。     

Seroepidemiology of hepatitis B virus infection among children in Mongolia: Results of a nationwide survey

BACKGROUND: Because Mongolia is one of the highly endemic countries for hepatitis B virus (HBV) infection in the world, hepatitis B (HB) vaccine was introduced into the National Expanded Program on Immunization in 1991. However, relatively few data are available concerning HBV infection among children born after the start of the program, so far. The aim of the present paper was to describe the seroepidemiology of HBV infection among primary school children using representative national data. METHODS: In 2004, a nationwide school-based cross-sectional serosurvey was carried out throughout Mongolia, covering both urban and rural areas. Serum samples were tested for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc) and hepatitis B e antigen (HBeAg) as well as for liver enzymes. RESULTS: A total of 1145 children aged 7-12 years were studied, which represents nearly 2% of the second grade population of elementary schools in Mongolia. The overall prevalence of HBsAg and anti-HBc was 5.2% (95% confidence interval [CI]: 3.9-6.5%) and 15.6% (95%CI: 13.5-17.7%), respectively. Among HBsAg-positive children 67.8% (95%CI: 55.9-79.7%) were also positive for HBeAg. The prevalence of chronic HBV infection increased by age and was significantly higher among children from rural areas compared to those from urban areas (7.7% vs 3.0%; P < 0.001). In the multivariate logistic regression analysis, rural residence (odds ratio [OR]: 2.57; 95%CI: 1.45-4.58), male sex (OR: 1.9; 95%CI: 1.08-3.26) and age (OR: 1.5; 95%CI: 1.10-2.05) were independent demographic predictors for chronic HBV infection. CONCLUSIONS: The prevalence of chronic HBV infection has been decreasing in the Mongolian young generation, most likely due to infant HB vaccination. However, significant rural-urban differences in the prevalence of HBV infection were found that demand further investigation to estimate the potential causes.     

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目的 探讨乙型肝炎病毒携带产妇所生新生儿血清乙型肝炎病毒标志物(HBV-M)转归.方法 2001年3月至2006年3月在暨南大学附属第一医院进行产前检查的500例HBsAg阳性产妇所生新生儿,根据母亲HBeAg状态分为HBeAg阳性组144例,HBeAg阴性组356例.两组新生儿在出生12 h内均注射乙型肝炎免疫球蛋白100 IU,并按常规0、1、6方案分别在出生时、1月龄和6月龄注射基因重组乙型肝炎疫苗5μg,注射主被动免疫前分别抽取外周静脉血检测HBV-M.结果 两组新生儿出生时外周血HBsAg、HBeAg均阳性者分别为24例和9例,追踪至6月龄时HBsAg阳性例数分别为10例和5例,HBsAg阴转率差异无统计学意义.两组新生儿出生时HBsAg阳性、HBeAg阴性者分别为4例和21例,追踪至6月龄时,HBsAg阴转率分别为100%和85.7%.出生时HBsAg阴性、HBeAg阳性者,HBeAg阳性组为29例,占20.1%,显著高于HBeAg阴性组比例(P＜0.01),其6月龄HBsAg阳转率为6.9%,明显低于HBeAg阴性组(P＜0.01).在接受全程主被动免疫的情况下,HBeAg阳性组新生儿6月龄HBsAg和HBsAb阳性率分别为9.7%和67.4%,HBeAg阴性组分别为3.1%和78.1%,两组比较差异有统计学意义(P＜0.05).结论 新生儿出生时外周血HBsAg阳性不能作为判断宫内感染的指标,HBeAg阳性新生儿预后与母亲HBeAg状态密切相关,母亲HBeAg阳性会抑制新生儿对乙型肝炎疫苗的反应.     

Retreatment with higher dose interferon alpha in children with chronic hepatitis B infection.

BACKGROUND: More than 50% of children with chronic hepatitis B infection do not respond to interferon-alpha (IFN-alpha) treatment and are prone to have progressive liver disease. The best treatment modality is unknown in these children. The aim of this study was to evaluate the possible benefit of a second higher dose IFN-alpha therapy for children with chronic hepatitis B diseases who failed previous therapy. METHODS: Twenty-four children with chronic hepatitis B infection who had not responded to previous IFN-alpha treatment were enrolled into the study. All were hepatitis B virus DNA- and hepatitis B e antigen-positive for >6 months after initial treatment. They received 10 megaunits (MU)/m2 of IFN-alpha 2a three times a week for 24 weeks. Liver function tests, hepatitis B virus markers and hepatitis B virus DNA were determined regularly during treatment and follow-up. A complete response was defined as clearance of both hepatitis B virus DNA and hepatitis B e antigen (HBeAg). RESULTS: At the end of therapy 8 (33.3%) patients cleared hepatitis B virus DNA and seroconverted to anti-HBeAg. Patients were followed for an average period of 12.2 +/- 4.7 months after retreatment. During follow-up an additional 4 patients cleared hepatitis B virus DNA and seroconverted to anti-HBe, whereas one seroconverted patient became HBeAg-positive again. Thus 11 patients (45.8%) had complete response at the end of the follow-up period. Alanine aminotransferase normalized in 11 responder patients and in 5 nonresponders. Positive predictive factors were low baseline titers of hepatitis B virus DNA and elevated transaminase values (> 100 IU/l). CONCLUSIONS: IFN-alpha retreatment with a higher dose may be an alternative modality for treatment of children with chronic hepatitis B infections who failed previous IFN-alpha, especially in those with favorable predictive factors.     

Chronic hepatitis B infection: long term comparison of children receiving interferon alpha and untreated controls

OBJECTIVES: To investigate the virological outcome of chronic hepatitis B (CH-B) in children who received interferon alpha (IFN) compared with no treatment. METHODS: Seventy-four children with CH-B (median age, 6.1 years; 44 boys) selected from a cohort of 158 cases were included and divided into two groups: IFN-treated (n = 37) and control (n = 37). The controls were matched with the treated children by baseline alanine aminotransferase (ALT) levels, sex and age. The Kaplan-Meier method was performed to estimate the time to clearance of hepatitis B e antigen (HbeAg) and hepatitis B surface antigen (HbsAg). RESULTS: Mean duration of follow-up was comparable in two groups (5.2 +/- 3.8 years in treatment group versus 5.2 +/- 3.7 years in control group, NS). HBeAg and HBsAg loss occurred in 20 (54.1%) and three treated children versus 13 (35.1%) and one untreated children (NS), respectively. The 7-year cumulative HBeAg and HBsAg clearance rates were 47.5% and 8.9% after the first visit in the treatment group versus 33.5% and 4.0% in untreated children (NS), respectively. Elevated baseline ALT (two times upper limit of normal) had a significant effect on the long-term cumulative rate of HBeAg seroconversion in treated patients (P = 0.01) but not in the untreated group. CONCLUSIONS: These findings show that the overall long-term virological outcome does not differ significantly between IFN-treated and untreated children but that a significant benefit of treatment on the long term rate of HBeAg seroconversion is obtained in children with higher baseline ALT levels.     

Treatment results of chronic hepatitis B in children: a retrospective study

In this retrospective study, we aimed to share our experience with different treatment modalities for chronic hepatitis B in a series of children. The study included 126 children (mean: 9.5 +/- 3.8 years). Normalization of alanine aminotransferase (ALT), loss of hepatitis B virus (HBV)-DNA and hepatitis B e antigen (HBeAg), and development of antibody to HBeAg (anti-HBe) altogether at the end of the treatment was considered as end of therapy response (ETR). Seroconversion ongoing one year after the cessation of therapy was considered as sustained response. Of the total children, 90 (71.4%) were treated, whereas the remaining were just followed-up. High-dose interferon (IFN)-alpha (10 MU/m2) alone, standard-dose IFN-alpha (6 MU/m2) plus lamivudine (4 mg/kg/d), high-dose IFN-alpha plus lamivudine, or lamivudine alone was used, IFN-alpha thrice weekly for six months, and lamivudine daily for one year. Of children who had completed their treatment, 34 (37.8%) achieved ETR. Sustained response rate was 36.7%. Response rates were different in the different treatment groups (p: 0.01). The highest response rate was observed in those who received standard-dose IFN-alpha plus lamivudine treatment (61.5%). Of children without treatment, one (2.8%) had anti-HBe seroconversion. Standard-dose IFN-alpha plus lamivudine treatment was found superior to the other treatment modalities. Predictors of ETR were similar to those found in previous studies.     

Tolerance of interferon-alpha therapy in children with chronic hepatitis B

OBJECTIVE: To assess the side-effects of interferon-alpha (IFN-alpha) therapy in children with chronic hepatitis B. METHODS: This prospective study was performed on one hundred children by interviewing the patients and their parents; clinical examinations and laboratory investigations were performed during and after therapy. RESULTS: The most frequent side-effects of IFN-alpha therapy were fever, flu-like symptoms, and headaches. Lowering of the mean haemoglobin level, leukocyte and platelet count was significant, but transient during INF-alpha treatment. No increase in autoantibody titres or significant alterations in thyroid function was observed. Twelve months after treatment, hepatitis Be antigen (HBeAg) elimination and alanine aminotransferase (ALT) normalization was achieved in 46% of the children; HBeAg and hepatatis B surface antigen (HBsAg) elimination, together with ALT normalization, was achieved in 14% of the cases. CONCLUSION: The side-effects of the IFN-alpha therapy in children such as fever, flu-like symptoms and bone marrow suppression are common, but transient and mild.     

Interferon treatment for chronic hepatitis B: enhanced response in children 5 years old or younger

OBJECTIVE: To test the hypothesis that there is an improved response to interferon in children with chronic hepatitis B (HBV) who are < or =5 years of age. STUDY DESIGN: Retrospective chart review of 22 consecutive children with chronic HBV (ages 17 months to 17 years; median, 83.9 months; 14 male, 8 female) treated with interferon-alpha2b. RESULTS: Ten patients (48%) responded to treatment [HBeAg (-), Anti-HBe (+), HBV DNA (-), HBsAg (+) and normal alanine aminotransferase/aspartate aminotransferase (ALT/AST) at 6 months after treatment], and 5 seroconverted HBsAg [above plus HBsAg negative and anti-HBs (+)]. Seven of 9 patients (78%) < or =5 years of age responded (5 cleared HBsAg). Three of 13 patients (23%) >5 years of age responded. Patient age at treatment was significantly lower in responders (63 +/- 70 months) versus nonresponders (104 +/- 55 months, P =.005). AST, ALT, and HBV DNA at the start of treatment were not different between responders and nonresponders or between patients < or =5 and >5 years old. CONCLUSIONS: Interferon treatment may be more effective in younger children with chronic hepatitis B.     

Factors affecting clearance of hepatitis B e antigen in hepatitis B surface antigen carrier children

To understand the natural history of chronic hepatitis B virus infection in children, we studied factors affecting the clearance of hepatitis B e antigen (HBeAg). One hundred sixty-nine apparently healthy children whose sera were positive for HBeAg and hepatitis B surface antigen (HBsAg) and who were recruited by screening were followed prospectively to delineate the HBeAg clearance rate. Another 59 carrier children visiting the outpatient clinic because of symptoms or abnormal liver function were studied for comparison. The annual HBeAg clearance rate was low (less than 2%) during the first 3 years of life but increased with age. The HBeAg clearance rate in children older than 6 years of age was lower in those whose mothers had HBsAg positivity (14.3%) than in those whose mothers had no detectable HBsAg (35.3%). Children who were brought for medical care had higher HBeAg clearance rates (42.4%) than those who were recruited by screening (14.6%) because immune clearance of hepatitis B virus and hence HBeAg often led to hepatocellular damage manifested by abnormal liver function profiles or by symptoms that had caused the parents to seek medical care for their children. We conclude that age, source of subject recruitment, and maternal HBsAg status are important factors affecting HBeAg clearance rate in HBsAg carriers.     

Chronic hepatitis B. Treatment in childhood with alpha-interferon]

BACKGROUND: In adults several trials of successful therapy for chronic hepatitis B using alpha-interferon with rates of seroconversion from HBeAg to anti-HBe of 30-40% have been reported. Despite the experiences in children are limited, alpha-interferon seems to be a promising drug in this age group as well. We report on our results in the treatment of chronic hepatitis B virus carrier using the recombination interferon alpha-2b. METHODS: 24 children aged 0.6-16 years with chronic active or chronic persistent hepatitis B were included in the study. 12 children received 9 million units of alpha-interferon/m2 body surface area three times a week during four months. 12 control patients were not treated. The follow-up period was 9-12 months after the beginning of therapy. HBsAg, anti-HBs, anti-HBe and Hepatitis-B-Virus-DNA were assessed during this time on a regular basis. RESULTS: Only seroconversion of HBe-Ag to anti-HBe was considered as response to interferon treatment. During the follow-up period anti-HBe could be detected in 5 (41.6%) of the treated and in one (8.3%) of the untreated children. In one case additional seroconversion of HBsAg to anti-HBs due to virus elimination was observed. In all children a marked reduction of viral replication could be shown. 9 patients cleared Hepatitis-B-Virus-DNA at least for one time during therapy. Alpha-interferon was well tolerated and no severe side effects were observed. CONCLUSION: Our results demonstrate that alpha-interferon can be successfully applied to a considerable number of children with chronic hepatitis B. In patients responding to alpha-interferon usually serum transaminases become normal and infectivity of the disease is markedly reduced. alpha-Interferon treatment should be primarily recommended for children with chronic active inflammation.     

Efficacy of combined interferon alpha and long-term lamivudine therapy in children with chronic hepatitis B

The aim of this study was to evaluate the efficacy of interferon alpha (IFN-alpha) and long-term lamivudine therapy in children with chronic hepatitis B and to determine the optimal duration of lamivudine therapy. Thirty-eight HBeAg-positive children simultaneously received IFN-alpha2a 5 MU/m2 to 10 MU/m2 for six months and lamivudine (4 mg/kg/day). Lamivudine was administered until anti-HBe seroconversion and was continued for six months in responders. During the five-year study period, we evaluated the efficacy of treatment, occurrence of YMDD mutants and adverse effects. During the study period, alanine aminotransferase (ALT) normalization, clearance of hepatitis B virus (HBV) DNA, HBeAg/anti-HBeAb, HBsAg/anti-HBsAb seroconversion, and histological response were noted in 27 (71.1%), 14 (36.8%), 13 (34.2%), 2 (5.2%) and 10 (47.9%) patients, respectively. Complete response was determined in 34.2% (13/38), and in 69.2% of these responders, response was achieved within 18 months. Breakthrough and YMDD mutant rates were 65.8% and 55.2%, respectively. Breakthrough time was a median 24 months and was associated with low baseline ALT level (p < 0.01). In conclusion, although lamivudine was used for a longer period, the response rate was not higher than in previous reports. We suggest that 18 months' duration of lamivudine treatment is sufficient for combination therapy.