阿德福韦酯联合拉米夫定治疗失代偿期乙型肝炎肝硬化18例疗效观察

目的观察阿德福韦酯联合拉米夫定治疗失代偿期乙型肝炎肝硬化的短期疗效和安全性。方法18例患者在保肝、对症支持等综合治疗的基础上加用阿德福韦酯（名正）10mg和拉米夫定100mg口服,疗程24周,比较患者治疗前后临床表现、生化学指标、病毒学改变情况。结果16例（88．9％）患者治疗后病情缓解稳定,Child—Pugh积分下降,肝功能好转或恢复正常;所有患者HBV—DNA水平明显下降,12周时1例HBeAg阴转,24周时阴转病例HBeAg／抗HBe血清学转换。结论阿德福韦酯联合拉米夫定治疗失代偿期乙型肝炎肝硬化可迅速显著地抑制HBV—DNA的复制,促进肝功能恢复,缓解病情发展．并且安全性好。     

两种阿德福韦酯治疗慢性乙型肝炎的疗效比较

［摘要］目的比较国产与进口阿德福韦酯治疗慢性乙型肝炎的疗效。方法选取门诊慢性乙型肝炎患者148例,分为两组。治疗组78例,给予国产阿德福韦酯胶囊10 mg&;#8226;d 1,对照组70例,给予进口阿德福韦酯片10 mg&;#8226;d 1,qd,po;疗程均为104周。定期检测两组的血清丙氨酸氨基转移酶（ALT）复常率、乙型肝炎病毒脱氧核糖核酸（HBV DNA）聚合酶阴转率、HBeAg/抗HBe血清转换率。结果两组患者在治疗后第4,12,24,52,78,104周的ALT复常率、HBV DNA阴转率、HBeAg/抗HBe转换率均差异无显著性。结论国产与进口阿德福韦酯治疗慢性乙型肝炎的有效率、不良反应发生率差异无显著性,但成本间差异有显著性。国产阿德福韦酯是较为经济、实用的方案。     

阿德福韦酯结合拉米夫定对慢性乙型肝炎肝硬化的疗效探讨

目的探讨阿德福韦酯结合拉米夫定对慢性乙型肝炎肝硬化的疗效。方法对我院125例慢性乙型肝炎肝硬化患者分别采用单药和结合药物进行治疗,对其HBV DNA阴转率及HBeAg阴转率和肝纤维化指标进行检测分析。结果结合组HBV DNA阴转率及HBeAg阴转率均较单药组高;结合组患者治疗前后的纤维化指标差异明显,且差异较单药组显著。结论阿德福韦酯结合拉米夫定对慢性乙型肝炎肝硬化的疗效明显优于单用阿德福韦酯或拉米夫定,在临床上值得广泛应用。     

阿德福韦酯治疗乙肝肝硬化患者的疗效分析

目的探讨阿德福韦酯治疗乙肝肝硬化患者的疗效。方法回顾分析2008年1月至2009年12月我院门诊和住院治疗的80例乙肝肝硬化患者的临床资料。结果 2组治疗后HBV DNA及HBeAg阴转率的比较,治疗组中HBeAg/HBeAb的血清学转换5例（13%）,而对照组患者无血清学转换。治疗组HbeAg阴转与对照组比较,差异有统计学意义（χ^2=4.0530,P〈0.05）。治疗组HB-VDNA阴转与对照组比较,差异有统计学意义（χ^2=10.80,P〈0.01）。观察过程中未发现阿德福韦的相关不良事件发生。结论阿德福韦酯可显著改善患者的临床症状,降低失代偿期肝硬化的发展速度。     

阿德福韦酯联合天晴复欣治疗慢性乙型肝炎临床研究

为探讨慢性乙型肝炎的临床治疗新途径,选用阿德福韦酯与天晴复欣联合应用,把70例慢性乙型肝炎患者随机分为两组,一组阿德福韦酯和天晴复欣联合治疗,另一组仅予阿德福韦酯治疗,结果发现治疗组乙型肝炎病毒e抗原(HBeAg)阴转率和谷丙转氨酶(ALT)复常率均显著高于对照组;而两组乙型肝炎病毒氧核糖核酸(HBV DNA)阴转率差异无统计学意义.阿德福韦酯联合天晴复欣治疗慢性乙型肝炎可有效地提高HBeAg阴转率和ALT复常率.     

慢性乙型肝炎肝硬化失代偿抗病毒治疗探讨

目的探讨慢性乙型肝炎肝硬化失代偿期抗病毒治疗的临床疗效。方法将我院自2005年2月至2011年3月收治的慢性乙型肝炎失代偿期肝硬化患者89例分为对照组和观察组。对照组41例采用单独给予拉米夫定100mg/d治疗,观察组48例在对照组的基础上加用阿德福韦酯10mg/d,治疗24个月。观察比较两组治疗前后的肝功能指标(AST、ALT、TBiL、ALB)、HBV DNA及HBeAg阴转率、HBeAg/HBeAb血清转换率和病毒变异情况。结果治疗后观察组患者肝功能指标比对照组有明显改善(P<0.01);观察组患者HBVDNA及HBeAg阴转率、HBeAg/HBeAb血清转换率明显高于对照组(P<0.05);两组患者的病毒变异率无显著性差异(P>0.05)。结论拉米夫定联合阿德福韦酯治疗失代偿期肝硬化可有效延缓或阻止肝硬化的进一步发展、改善肝功能,并能稳定或改善失代偿期肝硬化;病毒变异率低,且无严重的不良反应,治疗效果良好。     

优化方案治疗阿德福韦酯初治失败的慢性乙型肝炎患者的疗效分析

目的观察恩替卡韦单药序贯与拉米夫定联合阿德福韦酯治疗阿德福韦酯初治失败的慢性乙型肝炎患者的临床疗效及安全性。方法选择阿德福韦酯初治失败的慢性乙型肝炎患者213例．随机分为A组104例、B组109例;A组患者改用恩替卡韦单药治疗,B组患者予以拉米夫定联合阿德福韦酯治疗;至48周时分别观察、比较其血清HBV DNA水平中位数下降幅度、血清HBV DNA阴转率、HBeAg转阴率、生化学应答率。血清HBV DNA阴转患者继续原方案治疗至96周,并观察其维持血清HBV DNA阴转率、HBeAg转阴率、HBV基因耐药变异率及不良反应。结果治疗48周,两组患者血清HBV DNA水平中位数下降幅度、血清HBV DNA阴转率、HBeAg转阴率及生化学应答率,差异均无统计学意义（P均〉0．05）。血清HBV DNA阴转患者继续原方案治疗至96周．两组患者维持血清HBV DNA阴转率、HBeAg转阴率及HBV基因耐药变异率．差异均无统计学意义（P均〉0．05）。两组患者均无严重不良事件。结论阿德福韦酯初治失败的慢性乙型肝炎患者予以拉米夫定联合阿德福韦酯治疗或改用恩替卡韦单药治疗．均能取得较好的临床疗效;两种优化方案维持血清HBV DNA阴转率、HBeAg转阴率率及HBV耐药变异率均无明显差异,安全性良好均适用于患者临床治疗。     

拉米夫定联合阿德福韦酯治疗代偿期乙型肝炎肝硬化的临床分析

目的分析研究拉米夫定联合阿德福韦酯治疗代偿期乙型肝炎肝硬化的临床效果。方法随机数字选取我院收治的76例代偿期乙型肝炎肝硬化患者,均分为两组,对照组采用阿德福韦酯治疗,每次10 mg,每天1次;研究组采用拉米夫定联合阿德福韦酯治疗,每次100 mg拉米夫定,每天1次;10 mg阿德福韦酯,每天1次;比较两组患者的治疗效果。结果治疗后比较两组患者的总胆红素、天冬氨酸转氨酶以及丙氨酸转氨酶水平有明显差异,P<0.05有差异有统计学意义,两组患者治疗前HBV DNA水平无明显差异,治疗后HBV HDN明显就降低,较治疗前差异显著(P<0.05),研究组HBV DNA降低程度明显比对照组高,其HBV DNA转阴率也较对照组相比(P<0.05)两组患者治疗后均无明显不良反应。结论拉米夫定联合阿德福韦酯治疗代偿期乙型肝炎肝硬化,可有效改善患者的肝功能,且耐受性良好,安全可靠,值得应用推广。     

替比夫定联合阿德福韦酯对 HBeAg 阳性慢性乙型肝炎的疗效观察

目的：探讨替比夫定联合阿德福韦酯对HBeAg阳性慢性乙型肝炎患者的疗效。方法将76例慢性乙型肝炎患者分为干扰素组和替比夫定组,干扰素组应用聚乙二醇干扰素α-2a联合阿德福韦酯,替比夫定组给予替比夫定联合阿德福韦酯,治疗48周,观察血清谷氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的含量和正常化率及血清HBsAg、HBeAg和乙肝病毒（HBV） DNA的含量及HBeAg阴转率和血清转换率及HBV DNA低于检测下限值率变化。结果2组治疗后24周和48周ALT和AST的含量及血清HBsAg、 HBeAg和HBV DNA的含量均明显降低（ P ＜0．01）,而替比夫定组治疗后降低量更显著;ALT和AST正常化率,HBeAg阴转率和血清转换率及HBV DNA低于检测下限值率显著增加（ P ＜0．01）,而替比夫定组治疗后的增加量更显著。结论替比夫定联合阿德福韦酯的治疗效果比干扰素联合阿德福韦酯的治疗更加显著。     

阿德福韦酯治疗失代偿期乙型肝炎肝硬化58例临床观察

目的观察阿德福韦酯治疗失代偿期乙型肝炎肝硬化的临床疗效。方法 58例失代偿期乙型肝炎肝硬化患者,随机分为对照组和治疗组,其中对照组予以拉米夫定治疗,治疗组应用阿德福韦酯治疗,比较两组患者的临床症状体征改善情况,治疗前后肝功能变化情况,治疗后血清HBV DNA转阴率比较,以及不良反应情况。结果治疗组临床症状体征明显改善,明显优于对照组（P〈0.05）;与对照组相比,治疗组TBiL、ALT、AST明显改善降低（P〈0.05）;而与本组治疗前组比,两组TBiL、ALT、AST均有不同程度的降低,其中治疗组下降幅度尤为明显（P〈0.05）;两组治疗后血清HBV DNA转阴率均有一定改善,与对照组相比,治疗组于治疗结束后后9~12个月复查血清HBV DNA,其转阴率明显改善（P〈0.05）;治疗组不良反应低于对照组。结论采用阿德福韦酯对失代偿期乙型肝炎肝硬化的治疗效果优于拉米夫定治疗。     

4种抗病毒方案治疗乙型肝炎后肝硬化失代偿期的成本-效果分析

目的:观察4种抗病毒方案治疗乙型肝炎后肝硬化失代偿期的成本-效果。方法:259例乙型肝炎肝硬化失代偿期患者按用药分组,分别给予拉米夫定、阿德福韦酯、拉米夫定+阿德福韦酯、恩替卡韦口服,疗程为48周,观察4组疗效并进行成本-效果分析。结果:拉米夫定组、阿德福韦酯组、拉米夫定+阿德福韦酯组、恩替卡韦组的成本分别为4972.8、2889.6、7862.4、13104.0元;HBV DNA转阴率分别为85.9%、88.3%、95.7%、95.5%;YMDD不变异率分别为90.6%、96.7%、100%、100%;HBV DNA转阴率成本-效果比分别为5789.1、3272.5、8215.7、13721.5;YMDD不变异率成本-效果比分别为5488.7、2988.2、7862.4、13104.0;在阿德福韦酯组的基础上,拉米夫定组、拉米夫定+阿德福韦酯组、恩替卡韦组HBV DNA转阴率增加单位效果所需成本分别为-86800.0、67200.0、141866.7,YMDD不变异率增加单位效果所需成本分别-34150.8、150690.9、309527.3。结论:拉米夫定+阿德福韦酯组方案为治疗乙型肝炎后肝硬化失代偿期最合理方案。     

拉米夫定联合阿德福韦酯治疗乙型肝炎肝硬化失代偿期患者的临床观察

目的:探讨拉米夫定(LAM)联合阿德福韦酯(AVD)治疗乙型肝炎肝硬化失代偿期的疗效、安全性。方法:选择2006年6月～2008年6月门诊和住院乙型肝炎肝硬化失代偿期患者93例,随机分为3组。A组单用LAM(100mg·d-1);B组采用ADV(10mg·d-1);C组采用ADV(10mg·d-1)、LAM(100mg·d-1)联合治疗;3组均治疗52周。结果:治疗52周时3组患者间ALT水平、HBeAg阳性患者血清转换率比较,差异均无统计学意义(P>0.05);C组患者HBVDNA水平达到检测水平以下的百分率与B组患者比较,有显著性差异(P<0.05);3组间肝功能Child-Pugh评分比较差异无统计学意义(P>0.05)。3组患者的基因型耐药率分别为21.9%(7/32)、0、0。结论:乙型肝炎肝硬化失代偿期采用LAM联合ADV治疗更安全有效。     

Treatment paradigms on hepatitis B e antigen-negative chronic hepatitis B patients

The primary goal of treatment in hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B (CHB) is potent and durable suppression of hepatitis B virus (HBV) replication. It results in biochemical and histological remission of CHB and is the prerequisite for the prevention of cirrhosis, its life-threatening complications and hepatocellular carcinoma. Responses that are durable after the cessation of treatment are referred to as sustained virological responses, whereas those persisting under therapy are referred to as treatment-maintained virological responses. Treatment paradigms of sustained virological response in HBeAg-negative CHB are practically restricted to conventional IFN-α and pegylated interferons (peg-IFNs), and are limited only to patients with compensated liver disease. Long-lasting maintained virological responses without HBV resistance in HBeAg-negative CHB are achievable by all approved nucleos(t)ide analogues (lamivudine, adefovir and entecavir) in highly variable rates, depending on their potency, rapidity of virological response and genetic barrier to resistance. The maintenance of response under 5 years of adefovir treatment represents the most effective treatment paradigm for HBeAg-negative CHB, whereas such long-term data with entecavir and tenofovir monotherapy may become available in the near future. In patients with lamivudine-resistant HBV mutants, the recommended treatment strategy is to add adefovir at the same time as continuing treatment with lamivudine. There are no treatment paradigms as yet of combination therapy from the very outset with two nucleoside analogues for use in treatment-naive patients.     

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。     

阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎的疗效观察

目的：探讨阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎的疗效及安全性。方法：选择68例拉米夫定耐药的慢性乙型肝炎患者予以阿德福韦酯10mg／d，疗程1年以上。于治疗前和治疗12、24、52周检测肝肾功能、HBVDNA定量、HBeAg、抗HBe，观察药物不良反应。结果：治疗12、24、52周时，HBVDNA定量较用药前平均分别下降1．6lg拷贝／mL（t=10．10，P〈0．01）、2．9lg拷贝／mL（t=13．01，P〈0．01）、4．5lg拷贝／mL（t=14．08，P〈0．01）；HBVDNA转阴率分别是4．41％、19．12％和54．41％：ALT复常率分别为19．12％、48．53％和70.59％；HBeAg阴转率分别为0％、19．44％和47．22％。常见不良反应有轻微乏力、右上腹不适、腹胀，有2例患者发生腹泻，1例血清肌酐轻微改变。结论：阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎的疗效肯定，安全性好。     

Adefovir dipivoxil in chronic hepatitis B infection

Adefovir dipivoxil, an acyclic nucleotide analogue, is effective for the treatment of chronic hepatitis B in both hepatitis B e antigen (HBeAg)-positive and -negative patients, with improvement in liver histology, hepatitis B virus (HBV) DNA levels, alanine aminotransferase levels, and HBeAg seroconversion (for HBeAg-positive patients). It is also effective against lamivudine-resistant strains of hepatitis B mutations. It has been studied in pre- and post-liver transplant patients. Compared to lamivudine, adefovir dipivoxil is associated with a much lower risk of emergence of drug-resistant HBV. Adefovir-associated resistant virus is susceptible to lamivudine therapy. The recommended dose of adefovir dipivoxil 10 mg is associated with low risk of nephrotoxicity. Adefovir dipivoxil can be recommended as a first-line treatment but can also be used in patients with chronic hepatitis B infection who are failing lamivudine therapy.     

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.     

复方鳖甲软肝片联合阿德福韦酯治疗慢性乙肝纤维化的临床观察

目的探讨复方鳖甲软肝片联合阿德福韦酯治疗慢性乙肝纤维化的临床效果和安全性。方法 50例符合标准的患者给予复方鳖甲软肝片和阿德福韦酯胶囊治疗,疗程12个月。结果治疗12个月后,50例患者显效30例、有效15例和无效5例,总有效率90.00%;肝功主要指标(ALT、AST和TBIL)水平较治疗前明显好转(P<0.05);血清肝纤维化指标(HA、PCⅢ、Ⅳ-C和LN)水平较治疗前显著降低,差异存在统计学意义(P<0.05);入组时FS值为(19.92±5.37)kPa,治疗12个月后降至(8.83±4.65)kPa;患者入组时HBV-DNA均为阳性,治疗12个月后42例患者HBV-DNA转阴,转阴率为84.00%。结论复方鳖甲软肝片联合阿德福韦酯治疗慢性乙肝纤维化,有效改善肝功能和肝纤维化指标,值得临床推广应用。     

Entecavir: a new nucleoside analog for the treatment of chronic hepatitis B infection

BACKGROUND: Chronic hepatitis B infection carries considerable risk for the development of cirrhosis and hepatocellular carcinoma. Treatment options are increasing but are limited to interferon alfa-2b, pegylated interferon alfa-2a, lamivudine, adefovir dipivoxil, and entecavir. Entecavir, a nucleoside analog, is the newest oral antiviral approved in the United States for treatment of chronic hepatitis B. OBJECTIVE. To review the available data for entecavir regarding its pharmacology, pharmacokinetics, safety, efficacy, and clinical use. METHODS. A MEDLINE, EMBASE, and Cochrane search of the English-language literature from January 1997-May 2006 was performed. Preapproval studies provided by the manufacturer and abstracts from recent scientific meetings on infectious disease and hepatology were also reviewed. RESULTS. Three phase III clinical trials representing more than 1600 subjects established the superior efficacy and equivalent safety of entecavir compared with lamivudine for treating patients who are hepatitis B early antigen (HBeAg) positive, HBeAg negative, or refractory to lamivudine. Entecavir resistance has not occurred in nucleoside-na?ve patients but may develop in those who already possess lamivudine resistance mutations. CONCLUSION. Trial results, along with previously published response rates for adefovir dipivoxil and interferon monotherapy, make entecavir the preferred first-line treatment option for patients with chronic hepatitis B who are nucleoside na?ve, HBeAg positive or negative, and have compensated liver disease. Both entecavir and adefovir dipivoxil maintain activity against hepatitis B virus in patients with chronic hepatitis B who are refractory to lamivudine, and both agents are reasonable first-line treatment options. Longer trials involving nucleoside-na?ve, lamivudine-refractory patients are needed to determine entecavir's optimal treatment duration, long-term safety, and durability of response, including rate of resistance.