共查询到20条相似文献,搜索用时 62 毫秒
1.
核苷(酸)类似物耐药变异对乙型肝炎病毒生物学特性的影响 总被引:1,自引:1,他引:1
目前,所有口服核苷(酸)类似物抗病毒药物,包括拉米夫定、阿德福韦、恩替卡韦、替比夫定等,在长期抗乙型肝炎病毒(HBV)治疗过程中都可能出现耐药。随着核苷(酸)类似物抗病毒药物在临床上广泛应用于治疗慢性乙型肝炎,HBV耐药问题日益凸显,成为制约慢性乙型肝炎抗病毒疗效的主要因 相似文献
2.
目前,所有口服核苷(酸)类似物抗病毒药物,包括拉米夫定、阿德福韦、恩替卡韦、替比夫定等,在长期抗乙型肝炎病毒(HBV)治疗过程中都可能出现耐药.随着核苷(酸)类似物抗病毒药物在临床上广泛应用于治疗慢性乙型肝炎,HBV耐药问题日益凸显,成为制约慢性乙型肝炎抗病毒疗效的主要因素.HBV发生耐药变异之后,其生物学特性,包括复制能力、分泌能力、包装能力和抗原性都可发生相应变化.本文就核苷(酸)类似物抗病毒药物耐药变异对HBV生物学特性的影响作一概述. 相似文献
3.
4.
核苷(酸)类药物耐药机制及其对策 总被引:3,自引:0,他引:3
乙型肝炎病毒(HBV)的感染呈世界性分布,我国属于乙型肝炎高发区,在慢性乙型肝炎的治疗过程中,抗病毒治疗是关键,其药物可以分为干扰素和核苷(酸)类两大类.目前在我国正式上市的核苷(酸)类抗病毒药物共有4种:拉米夫定、阿德福韦酯、恩替卡韦及替比夫定. 相似文献
5.
作为在临床一线长期从事乙型肝炎诊疗的专科医师, 我们亲身经历了乙型肝炎治疗理念发展变化的全过程:从"对症治疗"进展至"病因治疗"(抗病毒治疗);抗乙型肝炎病毒(HBV)药物, 从单一的普通干扰素发展到多种核苷(酸)类似物和聚乙二醇干扰素, 特别是高效、高耐药屏障的恩替卡韦(ETV)、富马酸替诺福韦二吡呋酯(TDF)、富马酸丙酚替诺福韦(TAF)和艾米替诺福韦(TMF)等核苷(酸)类似物的广泛应用, HBV抑制的疗效满意, 大多数经过抗病毒治疗的慢性乙型肝炎(CHB)患者病情得到有效控制、肝功能持续正常, 肝纤维化逆转者亦屡见不鲜, 发展至肝癌的患者显著减少。即使是乙型肝炎肝硬化患者, 抗病毒治疗后的预后亦明显改善。 相似文献
6.
7.
8.
目的 比较核苷(酸)类似物抗病毒治疗前后对肾小球滤过率的影响,分析可能的影响因素.方法 以慢性乙型肝炎患者为研究对象,分为恩替卡韦治疗组(0.5 mg/d)、阿德福韦酯治疗组(10 mg/d)和替比夫定治疗组(600 mg/d).观察抗病毒治疗52周后各组肾小球滤过率(GFR)的变化,并进行3组患者治疗前后HBeAg血清学转换率、GFR升高≥10mL/(min·1.73 m2)及治疗后GFR≥90 mL/(min· 1.73 m2)的比较,以及出现HBeAg血清学转换患者治疗前后GFR的比较.结果 替比夫定组在治疗52周后GFR升高(P<0.05);治疗前后GFR升高≥10 mL/(min·1.73 m2)的患者比例替比夫定组优于阿德福韦酯组(P<0.05).结论 替比夫定抗病毒治疗后慢性乙型肝炎患者GFR得到改善. 相似文献
9.
340例慢性乙型肝炎患者乙型肝炎病毒多位点耐药相关突变分析 总被引:8,自引:0,他引:8
目的 分析慢性乙型肝炎患者HBV逆转录酶基因与核苷(酸)类似物耐药相关的12个位点上的突变情况及其临床意义.方法 提取血清HBV DNA,扩增HBV逆转录酶基因,对PCR产物进行DNA双向测序,对测序成功的样本进行基因型分析.检测逆转录酶基因12个位点上的碱基突变情况,分析不同核苷(酸).类似物使用情况、患者的耐药相关突变情况及不同核苛(酸)类似物耐药的突变形式. 结果 检出拉米夫定耐药突变63例,阿德福韦耐药突变10例,恩替卡韦耐药突变8例,替比夫定耐药突变1例.拉米夫定耐药突变中以M204V和M204I最常见,前者通常伴随L180M突变,后者常单独出现,阿德福韦耐药中以N236T±A181位碱基替换为主;恩替卡韦耐药突变发生在拉米夫定耐药基础上,以T184位碱基替换为主;替比夫定的耐药突变为M204I.少数未接受过核苷(酸)类似物治疗的患者也可检出耐药相关突变.结论 检测HBV逆转录酶基因多位点耐药相关突变,有助于临床及时发现和确认乙型肝炎患者是否存在HBV耐药,合理进行抗病毒治疗. 相似文献
10.
11.
Niraj James Shah Mark M Aloysius Neil Rohit Sharma Kumar Pallav 《World journal of gastrointestinal pharmacology and therapeutics》2021,12(4):56-78
Chronic hepatitis B(CHB) continues to contribute to worldwide morbidity and mortality significantly. Scientists, clinicians, pharmaceutical companies, and health organizations have dedicated substantial Intellectual and monetary resources to finding a cure, increasing immunization rates, and reducing the global burden of CHB. National and international health-related organizations including the center for disease control, the national institute of health, the American Association for the study of liver disease(AASLD), The European association for the study of the Liver(EASL), The Asia Pacific association for the study of the Liver(APASL) and the world health organization release periodic recommendations for disease prevention and treatment. Our review of the most recent guidelines by EASL, AASLD, APASL, and Taiwan Association for the Study of the Liver revealed that an overwhelming majority of cited studies were published before 2018. We reviewed Hepatitis B-related literature published 2018 onwards to identify recent developments and current barriers that will likely direct future efforts towards eradicating hepatitis B. The breakthrough in our understanding of the hepatitis B virus life cycle and resulting drug development is encouraging with significant room for further progress. Data from high-risk populations, most vulnerable to the devastating effects of hepatitis B infection and reactivation remain sparse. Utilization of systems approach, optimization of experimental models, identification and validation of next-generation biomarkers, and precise modulation of the human immune response will be critical for future innovation. Within the foreseeable future, new treatments will likely complement conventional therapies rather than replace them. Most Importantly, pragmatic management of CHB related population health challenges must be prioritized to produce real-world results. 相似文献
12.
《Annals of hepatology》2020,19(4):388-395
Introduction and objectivesUniversal vaccination at birth and in infancy is key to the elimination of chronic hepatitis B infection. We aimed to assess hepatitis B immune-prophylaxis and perinatal transmission knowledge, in a large and ethnically diverse cohort of previously pregnant North American women, chronically infected with hepatitis B.Materials and methodsThe Hepatitis B Research Network (HBRN) is comprised of 28 Clinical Centers in the United States and Canada. Female cohort participants were administered a questionnaire to assess: (1) their assertion of knowledge regarding HBV prophylaxis at birth, testing, and diagnosis of hepatitis B in their children, and (2) the percentage of affirmative to negative responses for each of the HBV-related interventions her child may have received. The relationship between asserted knowledge, actions taken and maternal demographics were assessed.ResultsA total of 351 mothers with 627 children born in or after 1992 were included. Median age at enrollment was 39.8 years. Mothers were mostly foreign-born with the largest percentage from Asia (73.4%) and Africa (11.7%). Of the 627 children, 94.5% had mothers who asserted that they knew whether their child had received HBIG or HBV vaccine at birth, for 88.8% of the children, their mothers indicated that they knew if their child was tested for HBV and for 84.5% of children, their mothers knew if the child was diagnosed with HBV infection. Among children whose mothers asserted knowledge of their HBV management, 95.3% were reported to have received HBIG or HBV vaccine, 83.4% of children were said to have been tested for HBV, and 4.8% of children were said to have been diagnosed with HBV. Younger maternal age was the only factor significantly associated with higher percentage of children for whom mothers reported knowledge of testing (p = 0.02) or diagnosis of HBV (p = 0.02).ConclusionsWhile high percentages of North American children had mothers asserting knowledge of HBV prophylaxis and testing, knowledge gaps remain, with mothers of 5.5–15.5% of children lacking knowledge of key components of the HBV prevention and diagnosis in the perinatal setting. Targeted education of HBsAg-positive mothers may aid in closing this gap and reducing vertical transmission. 相似文献
13.
目的观察拉米夫定对复发性慢性乙型肝炎患者的疗效和安全性。方法选择27例其他方法抗病毒治疗失败的慢性乙型肝炎患者,给予拉米夫定100mg口服,每日一次,连续服用12个月。结果治疗后12个月时ALT和血清总胆红素平均值(分别为52.7±26.5U/L和19.7±21.1μmol/L),与治疗前平均值(211.3±182.4U/L和54.6±28.8μmol/L)相比显著下降(P<0.01);其ALT复常率为88.9%(24/27),HBV DNA阴转率77.8%(21/27),HBeAg阴转率29.6%(8/27),HBeAg/抗-HBe血清转换率18.5%(5/27)。停药后6个月内有7例复发。治疗全程未见严重不良反应。结论拉米夫定治疗其他方法抗病毒治疗失败的慢性乙型肝炎患者也能够迅速抑制病毒的复制,使肝功能复常,而且安全、方便。 相似文献
14.
15.
目的 比较HBeAg阳性且HBV DNA高载量孕妇所生婴儿出生后应用不同剂量的乙型肝炎免疫球蛋白(HBIG)及乙型肝炎疫苗(HBVac)联合免疫接种后的母婴阻断效果,新生儿抗-HBs水平的差异. 方法 随机选取2009年至2013年我院产前检查并足月分娩的HBeAg阳性且建卡及临产均HBV DNA>1×106 IU/ml孕妇所生婴儿118例,婴儿出生后抽血检查HBV标志物和HBVDNA定量,据产妇及家属意愿抽血后按注射HBIG及HBVac剂量的不同分为3组:A组:58例,予HBIG 200 IU及HBVac 20 μ g肌肉注射;B组:35例,予HBIG 200 IU及HBVac 10 μg肌肉注射;C组:25例,予HBIG 100 IU及HBVac 20 μg肌肉注射,随访至7月龄.婴儿出生至7月龄的HBsAg、抗-HBs、HBeAg、HBV DNA变化采用重复测量方差分析;组间比较采用x2检验,P< 0.05为差异有统计学意义.结果 除去5例宫内感染婴儿,113例婴儿免疫接种后均产生抗-HBs.完成HBIG注射后,A、B、C三组1月龄婴儿时抗-HBs滴度分别为(263.56±50.98) mIU/ml、(231.06±74.07) mIU/ml和(99.23±29.82) mIU/ml,C组分别与A、B组比较,t值分别为15.01、8.41,P值均<0.001,差异均有统计学意义.A、B、C三组7月龄时婴儿抗-HBs滴度分别为(788.10±281.96) mIU/ml、(428.39±347.48) mIU/ml和(708.44±315.69) mIU/ml,B组与A、C组比较,t值分别为5.45、3.19,P值均<0.05,差异均有统计学意义. 结论 HBeAg阳性高病毒载量孕妇所生非宫内感染儿出生后应用HBIG及HBVac免疫接种能获得较好的免疫保护,应用HBIG 200 IU较100 IU,HBVac 20 μg较10 μg更安全可靠. 相似文献
16.
树突状细胞疫苗的制备及治疗慢性乙型肝炎的疗效观察 总被引:7,自引:2,他引:5
目的 探讨自体乙肝疫苗致敏的树突状细胞 (DC)的制备方法及其治疗慢性乙型肝炎 (CHB)的疗效。方法 取 CHB患者外周血 2 0 ml分离单个核细胞 ,加入重组人粒细胞—巨噬细胞集落刺激因子 (r GM- CSF)和白细胞介素 4 (IL- 4 )进行 DC体外扩增 ,于培养第 5天加入 5 0 μg/ m l乙型肝炎疫苗 ,7天收获细胞。 34例 CHB患者根据年龄和发病时间分为治疗 1(年龄 11~ 2 0岁 ,发病时间 0 .5~ 8.5年 )、2 (年龄 2 1~ 2 8岁 ,发病时间 3.5~ 18年 )、3(年龄 32~ 6 0岁 ,发病时间 10~ 4 2 .5年 )组 ,皮内回输 DC;对照组 CHB患者 (均为自愿停药者 ,2 0例 )注射等量生理盐水 ,均每周 1次 ,连续 8次。于回输 DC后 2周检测患者血清 HBV- DNA含量。结果 培养后可得到形态及功能典型的 DC,治疗 1、2、3组患者回输 DC后血清 HBV- DNA含量拷贝数均较对照组显著降低 (P<0 .0 1) ,总应答率 5 8.8% (2 0 / 34) ,对照组输注前后无明显变化 (P>0 .0 5 ) ;治疗 1组与 3组相比 HBV- DNA定量拷贝数降低幅度有显著性差异 (P<0 .0 1)。结论 DC可明显降低CHB患者血清 HBV- DNA含量 ,感染病毒时间短和 /或年龄小者降低幅度大 相似文献
17.
慢性乙型肝炎患者肝细胞内乙型肝炎核心抗原阳性的临床意义 总被引:1,自引:0,他引:1
目的探讨CHB患者肝组织HBcAg阳性的意义。方法对200例CHB患者应用荧光聚合酶链反应(FQ-PCR)法精确定量检测血清HBV DNA含量。患者均检测血清中HBeAg含量,同时进行肝活组织检查,应用免疫组织化学技术检测HBcAg情况,并进行相关性分析。结果按测定血清HBV DNA水平,分为A组(<3 log10拷贝/ml)20例,B组(≥3 log10拷贝/ml-<5 log10拷贝/ml)13例,C组(≥5 log10拷贝/ml~<6 log10拷贝/ml)24例,D组(≥6 log10拷贝/ml~<8 log10拷贝/ml)116例,E组(≥8 log10拷贝/ml)27例。肝组织HBcAg阳性者175例,占87.5%,A组HBcAg阳性率55.0%(11/20),B组53.8%(7/13),C组75.0%(18/24),D组96.6%(112/116),E组100.0%(27/27),HBcAg阳性率与血清HBV DNA水平之间呈显著正相关(r=0.80,P<0.01)。血清HBV DNA水平高低与HBeAg阳性率之间呈显著正相关(r=0.47,P<0.01)。其中20例HBV DNA阴性者中(A组),HBeAg阳性者5例(25%),HBcAg阳性者11例(55%);15例HBV DNA阴性且HBeAg阴性者中有7例HBcAg阳性,占46.7%。结论CHB患者肝组织HBcAg阳性能更可靠地反映肝细胞内HBV复制状态。检测肝组织内HBcAg对CHB患者疗效评价和对治疗反应性的预测更具有临床意义。 相似文献
18.
未接受抗病毒治疗的慢性乙型肝炎患者多聚酶P基因YMDD变异检测 总被引:4,自引:0,他引:4
目的 了解未经拉米夫定及干扰素抗病毒治疗的慢性乙型肝炎患者中HBV多聚酶YMDD变异情况。方法 应用错配PCR扩增方法检测病人血清HBV的YMDD位点,选择65例病史超过半年以上、肝功能异常、HBV DNA阳性的慢性乙型肝炎患者。结果 在65例患者中,YMDD变异阳性6例(9.07%),阴性59例,6例变异中2例为YIDD阳性,其中1例为YMDD野毒株和变异株混合存在,4例为YYDD阳性,其中1例为YMDD野毒株和变异株混合存在。结论 本检测方法简便、实用,在未经抗病毒治疗的慢性乙型肝炎患者中可存在YMDD变异株,其与野生株一样是自然存在的。 相似文献
19.
20.
目的观察中药燕滨扶正胶囊通过调节人体免疫机能对乙型肝炎病毒学指标的疗效。探讨中药治疗乙型肝炎HBsAg、HBeAg滴度的临床疗效。方法将CHB患者随机分为燕滨扶正胶囊组(治疗组,23例)和ADV组(对照组,21例)。治疗组单用燕滨扶正胶囊,1.5g/次,3次/d,不用任何保肝及抗肝纤维化药物;对照组服用ADV,10mg/次,1次/d,并根据病情需要加服复方牛胎肝等护肝药物。两组疗程均为48周。结果两组治疗前后HBsAg、HBeAg比较,差异均有统计学意义(P〈0.05,P〈0.01)。结论单纯运用中药“燕滨扶正胶囊”可使HBsAg、HBeAg、HBVDNA载量下降,改善脾肿大。 相似文献