替比夫定治疗慢性乙型肝炎的Meta分析

目的:评价替比夫定治疗慢性乙型肝炎患者的疗效及安全性。方法:检索替比夫定和拉米夫定治疗慢性乙型肝炎随机对照研究文献,对治疗效果、安全性等进行Meta分析。结果:替比夫定在生化反应、病毒学应答、降低HBeAg滴度、病毒学突破以及耐药发生率等方面优于拉米夫定,但在HBeAg和HBsAg转阴率上二者差异无统计学意义。随着疗程延长,替比夫定在HBeAg转阴率上高于拉米夫定,但不良反应和肌酸激酶升高的机会也随之增加。结论:替比夫定比拉米夫定具有更强的抑制乙肝病毒复制的作用,须重视不良反应。     

替比夫定联合阿德福韦酯治疗慢性乙型肝炎疗效观察

目的评价替比夫定联合阿德福韦酯治疗慢性乙肝的有效性。方法将84例患者随机分为替比夫定组、阿德福韦酯组、替比夫定联合阿德福韦酯组。观察3组HBeAg／HBeAb血清转换率、HBVDNA转阴率、ALT的变化情况。结果治疗后12周和治疗后24周三组血清HBVDNA、ALT均较治疗前明显降低,差异有显著性意义（P〈0．05）。治疗后12周联合治疗组与阿德福韦酯组血清HBVDNA比较,差异有显著性意义（P〈0．05）。治疗后12周联合治疗组与替比夫定组、阿德福韦酯组ALT比较,差异有显著性意义（P〈0．05）。治疗后24周联合治疗组与阿德福韦酯组HBeAg／HBeAb血清转换率、HBVDNA转阴率比较,差异有显著性意义（P〈0．05）。结论替比夫定与阿德福韦酯联合应用具有更强的抗病毒活性和快速抑制HBV-DNA的能力。两药合用既可以克服病毒对替比夫定的耐药性,又可以提高两药的抗病毒能力。     

Baseline Prognostic Factors and Statistic Model to Predict Early Virological Response in Telbivudine-Treated Patients With Chronic Hepatitis B

Background:

Hepatitis B virus (HBV) infection is still a worldwide disease, which may cause liver cirrhosis or even hepatocellular carcinoma. Telbivudine is a potent nucleoside analogue used in the treatment of chronic hepatitis B (CHB); however, drug resistance has remained a challenge. As early virological response can predict long-term efficacy of nucleotide analogue treatment, numerous studies have been conducted in this area.

Objectives:

The aim of this study was to establish baseline prognostic factors and a statistical model to predict early virological response in telbivudine-treated CHB patients.

Patients and Methods:

One hundred and eight CHB patients without any experience of nucleotide analogue therapy were assigned to receive telbivudine (600 mg, once daily) for at least 24 weeks, and then were followed up every two weeks. Cox proportional hazard regression model analyses were employed to evaluate baseline variables, and further developing a statistical model to predict early virological response.

Results:

Negative family history of HBV infection (P = 0.000235), baseline higher serum TBIL (P = 0.038714) and AST (P = 0.020684) concentrations, and lower level of HBV-DNA (P = 0.0034784) were identified to be associated with higher possibility of early virological response. A model was established based on these variables to calculate the risk scores (R) for CHB patients. R > -0.38 suggested early virological response to telbivudine. The model was validated among an independent set of 20 patients.

Conclusions:

Family history as well as baseline bilirubin, AST and HBV DNA levels can predict early virological response. The model provides a better tool for response prediction based on the four prognostic factors.     

高载量慢性乙型肝炎病毒感染孕妇晚孕期应用替比夫定的临床观察

目的：观察高载量慢性乙型肝炎病毒（HBV）感染孕妇晚孕期应用替比夫定（LdT）抗病毒治疗的疗效、安全性及其阻断母婴垂直传播的作用。方法选取2012年3月至2013年2月于江苏省常州市第三人民医院妇产科门诊进行产前检查的60例慢性 HBV感染孕妇为研究对象,并按照不同用药方式,将其分为LdT组（n=30）和对照组（n=30）（本研究遵循的程序符合江苏省常州市第三人民医院人体试验委员会所制定的伦理学标准,得到该委员会批准,分组征得受试对象本人的知情同意,并与之签署临床研究知情同意书）。两组患者年龄、体质量、孕龄等一般资料比较,差异无统计学意义（P＞0.05）。LdT组孕妇自孕龄为28~32孕周开始口服LdT（600 mg/d）,对照组孕妇未接受抗HBV感染治疗。检测两组孕妇孕龄为28~32孕周前及分娩时血清 HBV DNA载量,LdT组服药期间肝、肾功能水平,新生儿娩出时脐静脉血 HBV DNA载量,所生婴儿月龄为7个月时血清 HBV表面抗原（HBsAg）情况。观察 LdT组孕妇的药物不良反应。结果①两组孕妇孕龄为28~32孕周前血清 HBV DNA载量比较[（1.12±1.46）×108拷贝/mL vs.（9.01±6.65）×108拷贝/mL],差异无统计学意义（t=0.73,P=0.24）;②LdT 组孕妇分娩时（治疗后）HBV DNA载量下降均＞102拷贝/mL,其抗病毒治疗有效率达100%,且两组分娩时 HBV DNA载量＜5.6×103拷贝/mL孕妇数比较,差异有统计学意义（χ2=12.00,P＜0.01）;③LdT 组出现丙氨转氨酶（ALT）轻度升高孕妇为7例（23.3%）,无一例孕妇出现肾功能异常,治疗期均未出现药物不良反应。④LdT组脐静脉 HBV DNA载量＜5.6×103拷贝/mL 新生儿为30例（100%）,对照组为26例（86.6%）,两组比较,差异有统计学意义（χ2=4.29,P＜0.05）。⑤LdT组月龄为7个月婴儿血清 HBsAg 均呈阴性（100%）,对照组呈阴性婴儿为28例（93.3%）,两组比较,差异无统计学意义（χ2=0.52,P＞     

六味五灵片联合替比夫定治疗活动性慢性乙型肝炎肝硬化临床疗效观察

目的观察六味五灵片联合替比夫定治疗活动性慢性乙型肝炎（CHB）肝硬化的临床疗效。方法将72例HBV DNA、HBeAg阳性的CHB肝硬化患者随机分为治疗组和对照组,两组均为36例。治疗组给予六味五灵片联合替比夫定治疗,对照组单用替比夫定治疗,疗程均为24周。治疗前后分别检测患者肝功能、慢性HBV标志物、HBV DNA低于检测下限的比率。结果治疗组血清ALT、AST下降明显,与对照组比较,差异有统计学意义（P〈0.05）,治疗组HBeAg低于检测下限的比率及HBeAg/抗-HBe血清转换率均高于对照组,治疗组总有效率高于对照组,差异有统计学意义（P〈0.05）。结论六味五灵片联合替比夫定治疗活动性CHB肝硬化疗效显著,不良反应发生率小,疗效优于单一用药组,是治疗活动性CHB肝硬化的有效方法。     

恩替卡韦与替比夫定对治疗HBeAg阳性慢性乙型肝炎患者疗效及预测因素分析

目的 观察恩替卡韦与替比夫定治疗HBeAg阳性慢性乙型肝炎（CHB）患者的疗效及预测因素分析. 方法 将159例HBeAg阳性的CHB患者分为恩替卡韦分组（ETV组,81例）和替比夫定组（LDT组,78例）.治疗72周后,观察两组的应答情况[生化学应答率（丙氨酸转氨酶转复率）、完全病毒学应答率（HBV-DNA阴转率）、血清学应答率（HBeAg阴转率及HBeAg血清学转换率）],并且分析在治疗24周HBV-DNA转阴情况对72周疗效的预测影响.结果 两组患者治疗后各时间段的生化学应答率比较均无统计学意义（P均＞0.05）.治疗4周后ETV组和LDT组的HBV-DNA值与治疗前比较差异均具有统计学意义（P均＜0.05）,且治疗24周后ETV组的HBV-DNA值明显低于LDT组（P＜0.05）,但治疗72周后比较两组患者的完全病毒学应答率比较差异不具有统计学意义（P均＞0.05）.治疗各时间点ETV组比LDT组有着更高的血清学应答率,但差异不具有统计学意义（P均＞0.05）.治疗24周HBV-DNA转阴（HBV-DNA＜3lg拷贝/ml）的患者,72周具有更高的生化学应答率及血清学应答率（P均＜0.05）.结论 恩替卡韦与替比夫定对治疗CHB具有很好的疗效及较低的耐药率和不良反应,恩替卡韦在早期抗HBV-DNA优于替比夫定片,且治疗24周的HBV-DNA水平可预测长期疗效.     

两种不同方法评估替比夫定治疗慢性乙型肝炎患者肾小球滤过率的变化

目的：两种不同方法评估替比夫定治疗慢性乙型肝炎患者肾小球滤过率的变化。方法回顾性分析2009年9月至2012年9月在复旦大学附属华山医院单用替比夫定600 mg/d 口服治疗的慢性乙型肝炎患者资料。比较基于血清肌酐（Cr）及血清胱抑素 C 计算的肾小球滤过率。统计学处理采用t检验及秩和检验。结果患者共45例,男31例,女14例。患者 Cr 水平在抗病毒治疗前、治疗52周和104周三个时间点分别为（67．00＆#177;12．27）、（62．56＆#177;10．85）、（61．68＆#177;13．31）μmol/L,差异无统计学意义。患者血清胱抑素 C 水平在抗病毒治疗前、治疗52周和104周三个时间点分别为（0．8434＆#177;0．1113）、（0．7927＆#177;0．1204）、（0．7715＆#177;0．0915）mg/L。患者血清胱抑素 C 水平在抗病毒治疗52周和104周均较治疗前下降,差异有统计学意义（t＝2．063,P＝0．0421和t＝3．053,P＝0．0031）。基于血清肌酐计算的肾小球滤过率在抗病毒治疗前、治疗52周和104周三个时间点中位数分别为123．6、123．8、123．7 mL/min/1．73 m2,差异无统计学意义。基于血清胱抑素 C 计算的肾小球滤过率在抗病毒治疗前、52周和104周三个时间点分别为 （107．3＆#177;15．8）、（113．6＆#177;18．7）、（115．1＆#177;13．8）mL/min/1．73 m2,基于血清胱抑素 C 计算的肾小球滤过率在104周较治疗前升高,差异有统计学意义（t＝2．284,P＝0．0252）。结论在使用替比夫定治疗慢性乙型肝炎的患者中,肾小球滤过率有改善,基于血清胱抑素 C 计算的肾小球滤过率较基于血清肌酐计算的肾小球滤过率更加敏感。     

替比夫定对慢性乙型肝炎患者外周血CD4+CD25+调节性T细胞动态变化的影响及其临床意义

目的 探讨替比夫定抗病毒治疗过程中慢性乙型肝炎(CHB)患者外周血CD4+CD25+调节性T细胞(Tregs)比例的变化及其临床意义.方法 选取给予替比夫定抗病毒治疗的CHB患者36例,在治疗前及治疗后3、6、9个月时,分别以流式细胞仪检测外周血Tregs比例(以CD4+CD25<'high>T细胞作为Tregs),荧光定量PCR检测血清HBV DNA水平,酶联免疫吸附法检测HBV标志物,全自动生化分析仪检测ALT水平.结果 CHB患者外周血Tregs比例明显高于对照组(P<0.01).替比夫定抗病毒治疗过程中,CHB患者外周血Tregs比例逐步下降,治疗6、9个月时基本恢复正常水平;HBV DNA水平降至检测水平以下的CHB患者(30例)在Tregs比例明显下降的CHB患者中所占比例(7/7,100.0%)高于Tregs比例无明显下降的CHB患者(23/29,79.3%),但两者差异无统计学意义(P>0.05).治疗3、6、9个月时,HBeAg阴转率分别为11.1%、19.4%、25.0%,其中7例(19.4%)发生HBeAg血清学转换者在治疗3、6个月时Tregs比例均已降至正常人水平.结论 替比夫定抗病毒治疗过程中,能降低CHB患者外周血Tregs比例,治疗早期Tregs比例下降的患者HBeAg血清学转换率更高.     

替比夫定临床应用专题研讨会纪要

2009年2月7日,我国肝病和感染病领域部分专家在上海召开了"替比夫定临床应用专题研讨会",对替比夫定在临床应用中应注意的问题进行了深入讨论.     

Combination treatment in HBeAg-negative chronic hepatitis B

Chronic hepatitis B (CHB) represents an important public health problem. HBeAg-negative CHB is frequently associated with advanced liver disease and its prevalence is increasing. Monotherapy with either interferon (conventional or pegylated) or nucleoside/nucleotide analogues has its limitations. It has been suggested that a combination of these agents might increase antiviral efficacy. However, existing data do not support this hypothesis, even though combination treatment appears to reduce the risk for emergence of lamivudine resistance. Nevertheless, most existing combination studies are small, and it is possible that they have not been designed to detect significant differences between combination treatment and monotherapies. Another limitation of these studies is that, in most of them, lamivudine treatment was discontinued after 1 year, a strategy that is not followed in clinical practice. It was thought to be interesting to evaluate the combination of a short course of interferon (particularly pegylated) with the long-term administration of nucleotide or nucleoside analogues. The efficacy of combining pegylated interferon with the newer nucleotide or nucleoside analogues or of nucleotide with nucleoside analogues could also be evaluated. However, findings show that until more data are available, combination therapy cannot be recommended as first-line treatment in patients with CHB. On the other hand, add-on therapy with adefovir or tenofovir is the treatment of choice in patients who develop resistance to lamivudine. In patients with cirrhosis, a combination of lamivudine/adefovir may also be used as initial treatment; another option would be to add tenofovir in patients with an insufficient response to entecavir.