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。     

干扰素治疗儿童慢性乙型肝炎疗效预测因素的研究进展

干扰素虽已广泛应用于儿童慢性乙型病毒性肝炎的治疗,但其疗效受多方面因素的影响.研究发现,其疗效预测因素主要包括:治疗前患儿肝脏炎症的程度、血清转氨酶水平的高低、血清乙型肝炎病毒DNA水平及患儿的年龄、传播途径、干扰素剂量等,前三项是预测疗效的主要因素.     

重组α-2b干扰素治疗儿童慢性乙型肝炎疗效观察

目的观察基因重组α-2b干扰素治疗儿童慢性乙型肝炎疗效.方法将108例慢性乙型肝炎患儿分为治疗组78例、对照组30例,治疗组给予α-2b干扰素治疗,疗程半年,治疗后观察肝功能及HBV标志.结果治疗组HBeAg及HBV-DNA转阴率分别为39.7%和38.5%,均显著高于对照组(P<0.01),丙氨酸转氨酶(ALT)复常率、HBsAg转阴率分别为96.2%、5.1%,与对照组无显著性差异(P>0.05).结论基因重组α-2b干扰素是治疗小儿慢性乙型肝炎的有效药物,其疗效与ALT水平、年龄等因素有关.     

慢性乙型肝炎的治疗

随着对慢性乙型肝炎(乙肝)自然史的认识和新的抗乙肝病毒药物的不断问世,慢性乙肝的治疗和管理理念近年来有了革命性的变化。美国、欧洲、亚太等先后发布了慢性乙型肝炎的指南共识并不断予以更新,中华医学会肝病学分会和感染症学分会最近公布了我国的“慢性乙型肝炎防治指南”。兹将有关内容介绍如下。     

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。     

重组干扰素α-2b治疗小儿慢性乙型肝炎的临床研究

目的研究重组干扰素α-2b(干扰能)治疗小儿慢性乙型肝炎近期及远期疗效.方法观察组31例,用干扰能,≥7岁300万IU,肌内注射,每周3次,＜7岁100万IU肌内注射,每日1次,连续用27周.对照组26例,口服利肝隆,疗程亦为27周.结果疗程结束后,观察组丙氨酸转氨酶(ALT)复常率为93.5%,HBeAg阴转率为64.5%,HBV-DNA阴转率为61.3%,HBsAg阴转率为25.8%,对照组上述指标分别为30.8%、15.4%、15.4%、0.两组相比有显著差异,P＜0.01.停用干扰能后12个月,按本研究制定的疗效判断标准进行分析,观察组显效率、总有效率与对照组相比均有非常显著差异,均为P＜0.01.对部分病例进行4年的随访,观察组疗效优于对照组,各项指标相比均有显著差异.结论干扰能治疗小儿慢性乙型肝炎疗效较理想,治疗中未发现严重的副反应,随访4年,小儿生长发育未受到影响.     

干扰素α-1b治疗小儿慢性乙型肝炎疗效评价

目的 探讨干扰素α-1b治疗小儿慢性乙型肝炎(CHB)的疗效和安全性.方法 以27例小儿CHB为治疗组,用干扰素α-1b加利加隆片,对照组29例单用利加隆片剂,两组治疗时间同为6个月,随访6个月对治疗前后两组HBV、HBV DNA等指标进行观察.结果 治疗组的阴转率分别为37.1%、51.9%,明显高于对照组.结论 干扰素α-1b是治疗小儿CHB的首选药物.     

胸腺素α1联合拉米夫定治疗慢性乙型肝炎

目的探讨胸腺素α1(Tα1)联合拉米夫定(LAM)治疗慢性乙型肝炎(CHB)患儿的疗效。方法随机对66例12- 16岁体质量>33 kg CHB患儿随机分为Tα1 LAM组和LAM组;Tα1 LAM组为Tα1 6 mg,皮下注射,1次/d,连用5 d,后改为1.6 mg皮下注射,每周2次;LAM为1次/d,100 mg/次,顿服,共用26周后停用Tαa1,LAM继续应用至52周;LAM组只用LAM 100mg/次,顿服,共用52周。评价治疗前后患儿血清乙型肝炎病毒脱氧核糖酸(HBV—DNA)、HBV标志物、ALT变化。结果治疗52周时血清HBV-DNA转阴率Tα1 LAM组为100%,LAM组为93 7%;Tα1 LAM组在治疗52周时ALT复常率为87.1%;LAM组为78.1%;治疗52周时Tα1 LAM组乙型肝炎e抗原(HBeAg)血清转换率为58.1%,LAM组为21.9%, 两组比较差异有显著性。结论Tα1与LAM联合治疗CHB患儿疗效明显优于单一应用LAM。     

干扰素治疗慢性乙型肝炎43例

探讨干扰素治疗小儿慢性乙型肝炎（CHB）的疗效、安全性及其影响因素。方法用干扰素α－2b治疗43例小儿CHB患者,并以32例患儿做为对照。结果治疗组病毒复制标志的阴转率显著高于对照组;ALT复常率近期显著高子对照组,远期则无明显差别。治疗前ALT高值、血清HBV－DNA低水平及非母婴传播为干扰素治疗的有利因素。干扰素治疗组未见严重不良反应。结论干扰素可用于小儿CHB的治疗,疗效的高低取决于适当病例的选择。     

Combined lamivudine/interferon-alpha treatment in "immunotolerant" children perinatally infected with hepatitis B: a pilot study

OBJECTIVE: To investigate whether combining the antiviral effect of lamivudine with the immune-boosting action of interferon-alpha (IFN-alpha) is effective in treating hepatitis B virus (HBV) "immunotolerant" children. STUDY DESIGN: Twenty-three children (8 boys; mean age, 10 years) infected during the first year of life (17 Asian, 21 with normal aminotransferase levels, 15 with HBV-DNA >1000 pg/mL by hybridization and all with mild histologic changes) were treated with lamivudine (3 mg/kg) for 8 weeks alone and then lamivudine (3 mg/kg) and IFN-alpha (5 MU/m(2), 3 times weekly) in combination for 10 months. RESULTS: Seventy-eight percent became HBV-DNA negative at the end of treatment, 5 (22%) seroconverted to anti-HBe, 4 (17%) of whom achieved complete viral control, becoming persistently HBsAg negative and anti-HBs positive. None had YMDD mutations. The viral status of the patients has not changed after a median follow-up of 40 months (range, 36 to 48). CONCLUSIONS: This pilot study suggests that lamivudine pretreatment followed by a combination of lamivudine and IFN-alpha can induce complete viral control in HBV immunotolerant children, hitherto considered poor responders.     

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.     

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.     

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.     

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。     

Clinical significance of TT virus infection in children with chronic hepatitis B

BACKGROUND: The pathogenic role of TT virus (TTV) is not clear in patients with chronic hepatitis B. The aims of the present study were to determine the frequency of TTV positivity in serum and saliva samples and the possible role of TTV in children with chronic hepatitis B. METHODS: Sera and saliva from 29 healthy children and 25 children with chronic hepatitis B were tested for TTV-DNA by means of real-time polymerase chain reaction (PCR). RESULTS: Fifty-two percent (13/25) of the serum samples and 32% (8/25) of the saliva samples were positive for TTV-DNA in children with chronic hepatitis B. In healthy non-transfused children, TTV-DNA was detected in 58% (17/29) of the serum samples and 41% (12/29) of the saliva samples. Six (46%) of 13 children with chronic hepatitis and 10 (59%) of 17 healthy children had TTV-DNA positivity both in serum and saliva samples. Two serum samples were negative for TTV-DNA while the saliva samples were positive for TTV-DNA in chronic hepatitis B and control groups. Mean age, sex, serum alanine aminotransferase levels, hepatitis B virus (HBV)-DNA values were similar in TTV-positive and -negative children with chronic hepatitis B. However, total histologic activity index (HAI), periportal necrosis and portal inflammation scores were significantly higher in children with HBV-DNA and TTV-DNA viremia (P = 0.013, P = 0.008, P = 0.015, respectively). CONCLUSIONS: Because total HAI, periportal necrosis and portal inflammation scores were higher in children with TTV coinfection, TTV infection may contribute to the progression of liver damage in children with chronic hepatitis B.     

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.     

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.     

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。