恩替卡韦与拉米夫定对慢性乙型肝炎抗病毒作用与安全性的对照研究

目的:比较恩替卡韦和拉米夫定治疗慢性乙型肝炎的抗病毒作用与安全性。方法:33例未经抗病毒治疗的慢性乙型肝炎患者随机分为2组:恩替卡韦组(16例)、拉米夫定组(17例)。恩替卡韦组与拉米夫定组的剂量分别为0.5mg/d和100mg/d。疗程为48～96周。观察两药对HBV DNA、ALT、e抗原/e抗体血清转换的影响及其所致不良反应。结果:在治疗24周和48周时,恩替卡韦组和拉米夫定组未检测到HBV DNA的病例分别为56.25%,29.41%;87.50%,29.41%。e抗原阴转率与e抗原/e抗体血清学转换率以及不良反应2组无明显差异。结论:恩替卡韦与拉米夫定比较能更有效的抑制HBV复制,不良反应与拉米夫定相似。因此,可以用于慢性乙型肝炎的长期治疗。     

恩替卡韦对慢性乙型肝炎抗病毒治疗的临床分析

目的探讨恩替卡韦对慢性乙型肝炎的抗病毒治疗疗效。方法选择37例未经抗病毒治疗的慢性乙型肝炎患者随机分为治疗组(18例)和对照组(19例),治疗组给予恩替卡韦片0.5 mg/d口服,对照组给予拉米夫定片100 mg/d口服。疗程为48~96周。观察两药对HBV DNA、ALT、e抗原/e抗体血清转换的影响及其所致不良反应。结果在治疗24周和48周时,治疗组和对照组未检测到HBV DNA的病例分别为55.56%、31.58%,83.33%、36.84%。e抗原阴转率与e抗原/e抗体血清学转换率以及不良反应两组无明显差异。结论恩替卡韦能更有效地抑制HBV复制,不良反应与拉米夫定相似。     

恩替卡韦的药效学特征及抗乙型肝炎病毒试验荟萃

目的:为临床合理使用思替卡韦(ETV)提供理论支持。方法:系统性综述恩替卡韦的药物特征、抗病毒机制及抗乙型肝炎病毒(HBV)的临床试验。结果:ETV通过三磷酸盐与三磷酸脱氧鸟嘌呤核苷竞争,实现高选择性抗病毒,同时还能抑制HBV DNA多聚酶,临床应用安全性较高;临床病例研究证实,ETV可有效降低慢性HBV病例的血清HBV DNA载量,实现快速、高效抑制HBV复制,最终实现治疗目的,且其具有较高的基因耐药屏障功能,临床用药的耐药率极低。结论:恩替卡韦在抗HBV治疗中具有明显的优越性,可作为临床抗HBV治疗的首选药物。     

抗病毒治疗停药后乙型肝炎复发与血清HBV DNA水平的相关性分析

目的探讨乙型肝炎患者在接受抗病毒治疗停药后,乙型肝炎的复发情况与患者血清的HBV DNA水平的相关性。方法回顾性分析我院150例接受抗病毒治疗后达到停药标准的慢性乙型肝炎患者,其中乙型肝炎e抗原(HBe Ag)阳性90例,HBeAg阴性60例,其中接受阿德福韦酯治疗51例(ADV组),接受恩替卡韦治疗36例(ETV组),接受拉米夫定治疗63例(LAM组),收集患者治疗前及治疗1个月后的血清HBV DNA水平,比较停药48周后各组HBV DNA转阳情况,对比患者治疗停药后复发情况。结果 LAM组、ADV组和ETV组患者在停药48周时血清HBV DNA转阳率比较差异无统计学意义。当患者HBe Ag为阳性和阴性时,治疗前的HBV DNA水平越高,停药后复发率也越高。治疗1个月后,HBV DNA水平越低,停药后复发率也越低。结论慢性乙型肝炎患者的复发率与服用抗病毒药物治疗之前的血清HBV DNA水平、治疗1个月后的HBV DNA水平和血清中HBV DNA的水平下降幅度存在着相关性。     

恩替卡韦分散片初始治疗慢性乙型肝炎52例临床分析

目的评价恩替卡韦分散片治疗慢性乙型肝炎的抗病毒疗效及安全性。方法采用随机、双盲、阳性药物恩替卡韦片(博路定)平行对照试验方法。78例慢性乙型肝炎患者按2∶1的比例随机双盲分成2组,其中试验组52例,对照组26例。48周的双盲治疗期间,试验组口服恩替卡韦分散片0.5 mg/d,对照组口服恩替卡韦片0.5 mg/d。结果治疗12周时试验组和对照组血清HBV DNA水平分别下降4.81、4.76个log10。治疗24周时分别下降5.46、5.01个log10,治疗48周时分别下降5.20、5.16个log10,2组比较差异均无统计学意义。治疗12周时试验组与对照组血清HBV DNA水平完全抑制(<5×102copies/m L)率分别为44.23%和50.00%,治疗24周时分别为82.69%和76.92%,治疗48周时分别为78.84%和73.07%,2组比较差异均无统计学意义。治疗12周和24周时试验组和对照组血清HBV DNA水平较基线水平下降≥2log的比例均为100.00%,治疗48周时均为100.00%,2组比较差异均无统计学意义。治疗12周时试验组和对照组的ALT复常率分别为94.23%和92.30%,治疗24周时分别为96.15%和92.30%,治疗48周时分别为94.23%和92.30%,2组比较差异均无统计学意义.试验组和对照组均未发生任何严重不良事件。结论恩替卡韦分散片在治疗慢性乙肝方面具有显著的抗病毒作用,疗效与恩替卡韦片相当,是一种安全有效的抗乙肝病毒药物。     

恩替卡韦治疗慢性乙型肝炎后病毒学反弹与HBsAg水平的关系

目的 探讨HBsAg水平高低与慢性乙型肝炎抗病毒治疗结束后病毒学反弹的关系.方法 45例HBeAg阴性慢性乙型肝炎患者,服用恩替卡韦0.5 mg/d治疗2～3年结束时,依HBs Ag定量水平分为＞250 IU/ml(A)组25例和＜250 IU/ml(B)组20例,观察停药后12、24、36和48周HBV DNA定量和肝功能的变化.结果 停药时,两组HBV DNA定量均＜1000 copies/ml,肝功能均在正常范围,无统计学差异.停药后48周,A组中15例出现病毒学反弹,HBV DNA定量升高,伴肝功能异常10例;B组中1例出现病毒学反弹,HBV DNA定量升高,无肝功能异常发生(P＜0.05).结论 HBsAg水平越低,停药后其病毒学反弹可能性越小.     

恩替卡韦分散片治疗慢性乙型肝炎的临床疗效观察

目的 对恩替卡韦分散片在慢性乙型肝炎治疗中的疗效及安全性进行分析.方法 采取双盲、随机、双模拟以及阳性药物恩替卡韦片（博路定）平行对照的临床试验方法.在接受双盲治疗过程中,给予对照组29例患者恩替卡韦片及不含恩替卡韦分散片的模拟剂,温水送服1日1次,1次1片,0.5mg/片.而试验组则给予29例患者恩替卡韦分散片（润众）和不含恩替卡韦片的模拟剂,同时温水送服1日1次,1次1片,0.5mg/片.24周即可进行开放治疗,开放治疗期间,两组患者均同时服用恩替卡韦分散片,温水送服1日1次,1次1片,0.5mg/片.结果 在给予患者1日0.5mg恩替卡韦分散片治疗后,对12周和24周数据进行统计,不难发现,两组患者无论是血清HBV DNA完全抑制率,HbeAg转阴率,ALT复常率,抑或HbeAg/HbeAb血清转换率,HBV DNA下降≥2 log10的比例均没有明显差异.通过组内对比可以看到,24周后各项数据明显比12周时更高.开放期24周治疗后,两组患者的各项数据仍然保持较为明显的变化,且控制效果较好.结论 在慢性乙型肝炎治疗中恩替卡分散片能够很好地抑制乙型肝炎病毒复制,且能够很好地控制病情发展,同时还能够保持较高的安全性,是一种值得临床推广的慢性乙型肝炎治疗药物.     

核苷类药物在乙型肝炎后肝硬化治疗中的疗效分析

目的观察核苷类抗病毒药物拉米夫定(LAM)、阿德福韦酯(ADV)、恩替卡韦(ETV)在失代偿期乙型肝炎肝硬化患者中的疗效。方法失代偿期乙肝后肝硬化患者120名随机分为A、B、C三组,在内科综合治疗的基础上,A组单用LAM(100 mg/d),B组单用ADV(10 mg/d),C组单用ETV(O.5 mg/d)治疗,观察患者3,6,9及12个月时血清生化指标及病毒载量变化。结果经过核苷类似物抗病毒治疗后,各组HBV DNA载量在3,6,9和12个月后均有大幅度下降,ETV组患者HBV DNA载量下降及HBeAg阴转率显著高于LAM组和ADV组。结论 ETV更适合于失代偿期乙肝后肝硬化患者中的抗病毒治疗。     

慢性乙型肝炎2种抗病毒治疗方案的成本-效果分析

目的:比较2种抗病毒方案治疗慢性乙型肝炎的临床疗效,并进行经济学评价,以便为临床提供一种有效、经济的慢性乙型肝炎治疗方案。方法:采用回顾性调查方法,将接受抗病毒治疗的乙型肝炎患者67例分为拉米夫定(LVD)组和恩替卡韦(ETV)组,分别统计2组患者用药48周时的HBV-DNA阴转、HbeAg阴转和ALT复常情况,并统计用药金额,利用成本-效果分析方法对2种方案进行抗病毒疗效的经济学评价。结果:在HBV-DNA阴转率方面,ETV组好于LVD组(P<0.05);在HBeAg阴转率和ALT复常率方面,2组差异无显著性(P>0.05);经济学方面,LVD组和ETV组的成本-效果比分别是120.1和178.4,拉米夫定优于恩替卡韦。结论:从经济学方面来看,拉米夫定抗HBV的成本-效果比优于恩替卡韦。由于恩替卡韦在HBV-DNA阴转方面优于拉米夫定,而且拉米夫定长期使用导致的病毒变异较为多见,从而造成潜在的费用难以估计,其经济性值得进一步研究。     

恩替卡韦分散片治疗慢性乙型肝炎临床观察

目的 评价恩替卡韦分散片治疗慢性乙型肝炎的抗病毒疗效及安全性.方法 选慢性乙型肝炎患者88例,完全随机分为研究组(45例)和对照组(43例),分别应用恩替卡韦分散片和恩替卡韦片,均为10 mg/次,1次/d,连续口服48周.结果 治疗12周时,研究组和对照组的ALT复常率分别为68.9％(31/45)和62.8％(27/43);治疗24周时,分别为88.9％(40/45)和86.0％(37/43);治疗48周时分别为95.5％(42/44)和93.0％(40/43),组间差异均无统计学意义(均P＞0.05).治疗12、24和48周时,研究组血清HBeAg阴转率、HBeAg/HBeAb血清转换率与对照组的差异均无统计学意义(均P＞0.05).治疗24周时,研究组血清HBV DNA完全应答率略低于对照组,治疗48周时,研究组血清HBV DNA完全应答率略高于对照组,差异均无统计学意义(P＞0.05).治疗24、48周时,研究组与对照组血清HBV DNA水平下降≥2 lg拷贝/ml的比例均逐渐下降,组间差异无统计学意义(P＞0.05).研究组和对照组均未发生任何严重不良事件.结论 恩替卡韦分散片在治疗慢性乙型肝炎方面具有明显的抗病毒作用,疗效与恩替卡韦片相当,是一种安全有效的抗乙型肝炎病毒药物.     

Entecavir: a review of its use in chronic hepatitis B

Entecavir (Baraclude) is a novel nucleoside analogue of 2'-deoxyguanosine whose intracellular triphosphate form inhibits replication of the hepatitis B virus (HBV). In large, randomised, double-blind, phase III clinical trials in patients with chronic HBV infection, oral entecavir 0.5 or 1.0mg once daily for up to 96 weeks was superior to lamivudine 100 mg/day in improving hepatic histology, normalising aminotransferase levels and suppressing viraemia to levels undetectable by polymerase chain reaction (PCR) assay in nucleoside-naive hepatitis B e antigen (HBeAg)-negative (precore or core promoter mutants) and/or HBeAg-positive patients, and in lamivudine-refractory (persistent viraemia during lamivudine therapy) HBeAg-positive patients. In addition, the tolerability profile of entecavir was generally similar to that of lamivudine. Thus, entecavir is a primary option in the treatment of chronic HBV infection in both nucleoside-naive and lamivudine-refractory patients.     

Entecavir: a review of its use in the treatment of chronic hepatitis B in patients with decompensated liver disease

The oral deoxyguanosine nucleoside analogue entecavir (Baraclude?) has potent activity against hepatitis B virus (HBV) and a high genetic barrier to resistance. This article reviews the clinical efficacy and tolerability of entecavir in the treatment of chronic hepatitis B in patients with decompensated liver disease, as well as summarizing its pharmacological properties. Entecavir 1?mg/day was more effective than adefovir dipivoxil 10?mg/day in the treatment of patients with chronic hepatitis B and decompensated liver disease, according to the results of a randomized, open-label, multicentre trial. Patients were either nucleos(t)ide naive or lamivudine experienced. The reduction from baseline in HBV DNA levels at week 24 (primary endpoint) was significantly greater with entecavir than with adefovir dipivoxil. The proportion of patients with HBV DNA levels of <300 copies/mL was also significantly greater with entecavir than with adefovir dipivoxil at weeks 24, 48 and 96, as was the proportion of patients with ALT normalization. Entecavir 0.5 or 1?mg/day, tenofovir disoproxil fumarate 300?mg/day and a fixed-dose combination of emtricitabine/tenofovir disoproxil fumarate 200?mg/300?mg per day were effective in the treatment of chronic hepatitis B in patients with decompensated liver disease, according to the 48-week analysis of a randomized, double-blind, multicentre trial, primarily designed to examine tolerability endpoints. In this trial, over one-third of patients had received previous therapy with lamivudine for ≥6 months. The efficacy of entecavir in treatment-naive patients with HBV-related decompensated cirrhosis did not significantly differ from that seen in patients with chronic hepatitis B or compensated cirrhosis (compensated group), according to the results of a prospective, nonrandomized study. After 6 or 12 months of entecavir treatment, there were no significant differences between the decompensated and compensated groups in virological, biochemical or serological endpoints. In patients with decompensated cirrhosis, significant improvements from baseline in liver function were seen after 12 months of entecavir therapy. Oral entecavir was generally well tolerated in patients with chronic hepatitis B and decompensated liver disease, with most of the reported treatment-emergent adverse events consistent with decompensated liver disease. In the trial primarily designed to examine tolerability endpoints, there was no significant difference between patients receiving entecavir and those receiving tenofovir disoproxil fumarate with or without emtricitabine in terms of the proportion of patients experiencing tolerability failure or the proportion of patients with confirmed increases in serum creatinine levels of ≥0.5?mg/dL above baseline or confirmed serum phosphorus levels of <2.0?mg/dL at week 48 (co-primary endpoints). It has been suggested that the risk of lactic acidosis associated with oral nucleos(t)ide analogue therapy is increased in patients with highly impaired liver function. However, only one case of lactic acidosis was reported among entecavir recipients across two clinical trials in patients with chronic hepatitis B and decompensated liver disease. Moreover, small studies found that the risk of lactic acidosis was not increased in patients with chronic hepatitis B and decompensated liver disease who received entecavir, compared with patients with non-HBV decompensated liver disease. In conclusion, entecavir is a valuable agent for the first-line treatment of chronic hepatitis B in patients with decompensated liver disease.     

Efficacy of HBV-pulsed DCs in combination with entecavir in patients with chronic hepatitis B infection

Dendritic cells (DCs) are multifunctional cells that initiate adaptive immune responses. Patients with chronic hepatitis B virus (HBV) infection have reduced numbers of DCs which may be functionally impaired, a defect that may contribute to viral persistence. Autologous DC-based immunotherapy is considered to be a treatment option for chronic HBV infection (CHB). We evaluated the therapeutic efficacy of HBV-pulsed DCs in combination with the antiviral drug entecavir in patients with CHB. Eighty patients were divided into four groups: HBV-pulsed DCs only, HBV-pulsed DCs plus entecavir, entecavir only, and an untreated control group. Patients on combination therapy exhibited greater antiviral responses than patients on either monotherapy. The combination of HBV-pulsed DCs and entecavir resulted in the largest reduction in serum viral DNA levels and the highest percentage of virologic response. In addition, combination therapy resulted in viral e antigen (HBeAg) loss and seroconversion. These results suggest that the combination of HBV-pulsed autologous DCs and entecavir could be therapeutically advantageous for patients with CHB.     

阿德福韦酯联合恩替卡韦治疗对拉米夫定耐药的慢性乙型肝炎临床疗效观察

目的比较阿德福韦酯联合拉米夫定和阿德福韦酯联合恩替卡韦对拉米夫定耐药的慢性乙型肝炎患者的疗效。方法 140例对拉米夫定耐药慢性乙型肝炎的门诊患者随机分为两组:联合用药A组和联合用药B组。A组患者服用阿德福韦酯10mg/d,加服拉米夫定100mg/d,B组在服用阿德福韦酯时,服恩替卡韦0.5mg/d,所有患者均治疗2年。治疗前、治疗0.5、1、1.5和2年分别检测HBV-DNA和ALT。结果两组患者治疗后平均ALT水平均显著降低,HBV-DNA转阴率和ALT复常率显著增加,而联合用药B组明显优于A组。结论对于拉米夫定耐药的慢性乙型肝炎患者,可优先考虑采用阿德福韦酯联合恩替卡韦进行治疗。     

恩替卡韦治疗慢性重症乙型肝炎的疗效观察

目的:探讨恩替卡韦对慢性重症乙型肝炎的治疗意义。方法:将54例早、中期重症乙型肝炎患者分为对照组(26例)与治疗组(28例),对照组采用综合治疗,不包括干扰素和(或)核苷(酸)类似物等抗病毒药物,治疗组采用综合治疗加恩替卡韦(0.5mg,qd)。均治疗6周,每2周检测1次肝功能、乙肝两对半标志及HBV-DNA,疗程结束时记录患者的好转率。结果:在6周观察期间,治疗组患者血清HBV-DNA和总胆红素下降明显,与对照组比较有显著性差异;2组丙氨酸氨基转移酶、天门冬酸氨基转移酶、血浆白蛋白和凝血酶原时间也明显下降,2组比较无显著性差异;治疗组与对照组好转率分别为89.3%、84.6%,无显著性差异。结论:恩替卡韦可以迅速降低重症乙型肝炎患者血清HBV-DNA水平,促进胆红素的下降,改善肝脏功能,对患者的预后有帮助,可用于重症乙型肝炎治疗;但短期难以提高重症乙型肝炎患者的生存率。     

Adefovir dipivoxil in chronic hepatitis B: history and current uses

INTRODUCTION: The nucleotide analogue adefovir dipivoxil (ADV) was approved in 2002 for the treatment of chronic infection with hepatitis B virus (HBV), in both hepatitis B e antigen (HBeAg)-positive and -negative patients. ADV 10 mg daily has been associated with improved liver histology, decreased levels of HBV DNA and alanine aminotransferase (ALT), and seroconversion of HBeAg. AREAS COVERED: This paper reviews the use of ADV as a first-line treatment for chronic hepatitis B and as an add-on therapy in chronic HBV-infected patients with lamivudine resistance. In the years since its launch, clinical resistance to ADV has emerged, and tenofovir and entecavir have shown greater efficacy in reducing viral load. EXPERT OPINION: Many patients who started antiviral therapy with ADV (either as monotherapy or in combination with lamivudine) remain on this agent because they have undetectable viremia, but its future use will probably diminish because of the availability of more potent drugs. ADV is generally well tolerated, though the 10 mg dose is associated with low risk of nephrotoxicity.     

HBsAg 定 量对恩替卡韦治疗慢性乙型肝炎效果的预测价值

目的观察慢性乙型肝炎患者应用恩替卡韦治疗24周的HBsAg定量变化情况。方法58例慢性乙型肝炎患者接受恩替卡韦抗病毒治疗,分别检测并记录0、4、8、12、24周血清HBsAg及HBVDNA定量水平。结果恩替卡韦治疗后慢性乙型肝炎患者血清HBsAg及HBVDNA定量水平明显下降,差异有统计学意义（P〈0．05）,HBsAg定量与HBVDNA定量水平均呈正相关（P〈0．05）。结论HBsAg定量的变化可预测恩替卡韦治疗慢性乙型肝炎的疗效。     

国产恩替卡韦分散片对慢性乙型肝炎初次抗病毒的疗效分析

目的 比较国产恩替卡韦分散片与进口恩替卡韦及拉米夫定对慢性乙型肝炎初次抗病毒的疗效.方法 168例未接受过抗病毒治疗的慢性乙型肝炎患者完全随机分为3组:国产恩替卡韦组(54例),进口恩替卡韦组(56例),拉米夫定组(58例),治疗1年.观察3组患者治疗第12、24、48周的ALT复常率、HbeAg和HBVdNA的阴转率,平均血清HBVdNA基线水平.结果 治疗第12、24、48周国产思替卡韦组的ALT复常率、HbeAg和HBVdNA的阴转率均明显高于拉米夫定组[第12周分别为74.1％(40例)比51.7％(30例)、24.1％(13例)比8.6％(5例)、77.8％(42例)比55.2％(32例),第24周分别为85.2％(46例)比63.8％(37例)、27.8％(15例)比10.3％(6例)、81,5％(44例)比60.3％(35例),第48周分别为88.9％(48例)比69.0％(40例)、33.3％(18例)比13.8％(8例)、96.3％(52例)比67.2％(39例),均P＜0.05],与进口恩替卡韦组比较,差异均无统计学意义(均P＞0.05).结论 慢性乙型肝炎初次抗病毒治疗国产恩替卡韦分散片疗效明显高于拉米夫定,而与进口恩替卡韦片的疗效差异无统计学意义.