阿德福韦酯联合拉米夫定对YMDD变异的失代偿期乙型肝炎肝硬化临床观察

目的观察比较阿德福韦酯联合拉米夫定和单用阿德福韦酯治疗YMDD变异的失代偿期乙型肝炎肝硬化的疗效和安全性。方法将30例在拉米夫定治疗过程中出现YMDD变异的失代偿期乙型肝炎肝硬化患者随机分为两组(各15例),联合组:继续接受拉米夫定100mg/d治疗,全程联合阿德福韦酯10mg/d口服;单用组:拉米夫定100mg/d和阿德福韦酯10mg/d联合治疗3月后单用阿德福韦酯10mg/d口服,疗程1年以上,两组在保肝基础治疗上无差异。结果治疗48周时结果显示,联合组肝功能ALT、ALB改善优于单用组(t分别为3.30、4.06,P<0.01),HBV DNA阴转率显著高于单用组(x2=3.89,P<0.05)。结论阿德福韦酯对YMDD变异的失代偿期乙型肝炎肝硬化患者有良好的疗效和安全性,联合拉米夫定疗效更显著,能明显提高患者的生存质量,改善预后。     

拉米夫定联合阿德福韦酯治疗失代偿期乙型肝炎肝硬化的临床观察

目的研究拉米夫定（LAM）联合阿德福韦酯（ADV）治疗失代偿期乙型肝炎肝硬化的临床疗效。方法92例失代偿期乙型肝炎肝硬化患者在综合护肝及对症治疗基础上,联合组30例给予拉米夫定100mg/d和阿德福韦酯10mg/d口服;LAM组28例给予拉米夫定100mg/d口服;34例给予阿德福韦酯10mg/d口服。在治疗前和治疗6个月时观察肝功能、HBVM以及血清HBVDNA水平的变化。结果拉米夫定和阿德福韦酯联合组与拉米夫定组和阿德福韦酯组HBVDNA阴转率分别为80%、53.6%和41.2%,联合组明显优于单用组（P〈0.05）;肝功能Child-Pugh计分分别为7.0±1.1、7.7±1.2和7.8±1.3,联合组明显优于单用组（P〈0.05）。结论拉米夫定联合阿德福韦酯抗病毒治疗失代偿期乙型肝炎肝硬化优于单用拉米夫定或阿德福韦酯治疗。     

阿德福韦酯联合拉米夫定治疗失代偿性乙型肝炎肝硬化疗效观察

我院自2001年后试用拉米夫定治疗活动性、失代偿性乙型肝炎肝硬化并取得较好疗效,当部分患者出现YMDD变异产生耐药,改用阿德福韦酯口服治疗后,部分患者又发生阿德福韦酯耐药,引起病毒反弹及生化指标反弹。本组此类患者采用阿德福韦酯重新联用拉米夫定治疗取得很好疗效,报道如下：     

拉米夫定治疗失代偿期乙肝肝硬化的临床研究

目的观察拉米夫定对失代偿期乙肝肝硬化患者的治疗效果和安全性。方法60例患者Child-Pugh评分、基础情况相当，分为治疗组和对照组各30例，治疗组在常规治疗同时服用拉米夫定，每日100mg，对照组给予常规治疗。结果拉米夫定治疗随访时间中位数为2年2月。所有患者治疗3～6月后症状和体征逐渐改善，腹水消失。拉米夫定治疗组1年内血清HBV-DNA转阴率76．67％（23／30），血清白蛋白和PTA上升、总胆红素均有下降，Child-Pugh评分减少，2年生存率达93．33％，并发症及再次住院率明显下降。拉米夫定治疗出现YMDD变异率：1年为6．67％（2／30），2年为33．33％（10／30），出现病毒变异后及时加用阿德福韦酯的患者肝功能恢复良好。结论拉米夫定治疗能改善失代偿期乙肝肝硬化肝功能和提高生存率。一旦出现YMDD变异，及时加用阿德福韦酯等针对YMDD变异的抗病毒药物可抑制变异的HBV的复制，防止肝功能恶化。     

阿德福韦酯联合拉米夫定治疗早期乙肝肝硬化的临床分析

目的观察阿德福韦酯联合拉米夫定治疗早期乙肝肝硬化的临床疗效。方法将77例乙肝肝硬化患者分为联合治疗组45例,给予口服阿德福韦酯胶囊10mg／d和拉米夫定100mg／d;对照组32例,给予VI服拉米夫定100mg／d,治疗1年,观察HBV—DNA转阴率、酪氨酸-蛋氨酸-天冬氨酸-天冬氨酸（YMDD）变异率、肝功能及血小板等指标变化。结果联合治疗组HBV—DNA转阴率在各时间点均明显高于对照组,肝功能好转及血小板升高率也高于对照组,且时间明显提前。48周内联合治疗组无1例发生YMDD变异,对照组到48周时有19％的患者发生变异。病理检结果显示48周后联合组50％的患者改善,而对照组为36％。结论阿德福韦酯联合拉米夫定治疗早期乙肝肝硬化效果明显优于拉米夫定,抗病毒速度快、肝功能好转及病理改善率高,耐药突变率低。     

阿德福韦酯和拉米夫定治疗乙型肝炎肝硬化失代偿期的临床观察

目的观察阿德福韦酯和拉米夫定治疗肝炎肝硬化失代偿期患者48周的疗效和不良反应。方法采用随机分组法,将62例肝炎肝硬化失代偿期患者,随机分为阿德福韦酯组32例,给予阿德福韦酯10mg/d,拉米夫定组30例,给予拉米夫定100mg/d,疗程均为48周。均给予常规护肝及支持、对症治疗。观察两组患者的肝功能、HBeAg、HBV DNA、肝纤维化标志物Ⅲ型前胶原、Ⅳ型胶原、层黏连蛋白、透明质酸、肾功能及Child-Pugh分级、药物不良反应。结果两组患者肝功能各项指标的复常率、血清HBV DNA下降水平及转阴率、HBeAg转阴率及HBeAg/抗-HBe转换率均随着治疗疗程的延长而增加,但两组比较,差异无统计学意义。治疗至48周时拉米夫定组有2例发生YMDD变异,变异率6.7%,阿德福韦酯组无病毒变异发生。两组患者血清肝纤维化标志物治疗至24周时与治疗前相比明显下降,且随着疗程的延长进一步降低,两组比较差异无统计学意义。两组患者治疗前后Child-Pugh分级比较,差异无统计学意义。两组患者均未发现药物相关的肾功能损害,两组中各有2例患者出现轻度不良反应,但均能耐受。结论肝炎肝硬化失代偿期患者48周的抗病毒治疗,阿德福韦酯的疗效与安全性均与拉米夫定相似,而病毒耐药突变率较拉米夫定低。     

拉米夫定或阿德福韦酯选择性治疗失代偿性乙型肝炎肝硬化3年临床观察

目的观察拉米夫定或阿德福韦酯选择性治疗乙型肝炎肝硬化失代偿期患者长疗程疗效及治疗方案的选择。方法乙型肝炎肝硬化失代偿期患者65例,HBV DNA5 log10拷贝/mL者服用拉米夫定(100mg/d)或再联用阿德福韦酯(10mg/d);HBV DNA5 log10拷贝/mL者可单用拉米夫定或阿德福韦酯;病毒持续不下降或反弹要求拉米夫定联用阿德福韦酯。观察治疗前后患者临床症状体征、生化指标、病毒学改变情况。结果65例患者中43例生存至研究结束,3年生存率为66.1%。患者治疗后肝功能正常或好转,病情缓解稳定,生活质量改善,HBV DNA下降约3 log10拷贝/mL,Child-Pugh积分下降3。结论拉米夫定或阿德福韦酯选择性治疗乙型肝炎肝硬化失代偿期患者,可延长患者生存时间,改善肝功能,阻止病情进展,提高生活质量。     

阿德福韦酯联合大黄虫胶囊治疗失代偿期乙型肝炎肝硬化临床研究

目的：观察阿德福韦酯联合大黄廑虫胶囊治疗失代偿期乙型肝炎肝硬化的疗效和安全性。方法：61例失代偿期乙型肝炎肝硬化患者随机分成治疗组31例,对照组30例。两组在对症、保肝等常规治疗基础上给予阿德福韦酯10mg／次,1;K／d。治疗组在对照组基础上联合大黄座虫胶囊4米王／次,2次／d。疗程均为24周。结果：两组患者治疗后Child—Pugh评分下降,肝功能改善,肝纤维化指标、HBVDNA载量下降,HBeAg／HBeAb血清转换及彩超检查情况,配对比较差异有统计学意义。结论：阿德福韦酯联合大黄鹰虫胶囊治疗失代偿期乙型肝炎肝硬化,能改善患者肝功能,显著提高肝纤维化治疗效果,提高生存率,临床用药安全。     

替诺福韦酯和拉米夫定联合阿德福韦酯对乙型肝炎肝硬化患者疗效的比较

目的比较替诺福韦酯和拉米夫定联合阿德福韦酯对乙型肝炎肝硬化患者的疗效,为乙型肝炎肝硬化治疗提供一定的临床依据。方法选取我院乙型肝炎肝硬化患者共130例,实验组和对照组各65例。实验组接受替诺福韦酯(300 mg/d),对照组予以阿德福韦酯(10 mg/d)联合拉米夫定(100 mg/d),两组共治疗12个月,观察比较治疗前后肝功能、血清病毒学指标及甲胎蛋白(AFP)水平变化。结果经过治疗以后,两组患者ALT,AST,总胆红素(TBil),Child-Pugh评分,甲胎蛋白(AFP)较治疗前均显著降低,但实验组较对照组降低更加明显,其差异有统计学意义(P0.05)。治疗后,实验组HBV DNA、失代偿好转率明显高于对照组,其差异有统计学意义(P0.05)。两组患者在死亡率,肝癌发生率上差异无统计学意义(P0.05)。结论替诺福韦酯对于乙型肝炎肝硬化患者疗效优于拉米夫定联合阿德福韦酯,耐药发生率低。对于拉米夫定联合阿德福韦酯疗效欠佳的乙型肝炎肝硬化患者可以考虑改用替诺福韦酯。     

阿德福韦酯治疗失代偿期乙型肝炎肝硬化的临床观察

目的探讨国产阿德福韦酯（代丁）治疗失代偿期乙型肝炎肝硬化36周的疗效及安全性。方法将36例HBeAg／HBV DNA阳性的失代偿期肝硬化患者随机分为2组,均接受一般保肝、利尿及对症支持治疗,治疗组18例患者加用国产阿德福韦酯抗病毒治疗36周。结果在治疗36周结束时,治疗组患者血清生化学指标改善、HBV DNA水平下降及Child—Pugh分级评分与对照组相比,差异均有统计学意义;治疗组无不良反应发生。结论国产阿德福韦酯治疗乙型肝炎后失代偿期肝硬化疗效肯定,安全性良好。     

Determinants of early mortality and benefits of lamivudine therapy in patients with hepatitis B virus-related decompensated liver cirrhosis

Chronic hepatitis B infection (HBV) is a major health problem worldwide. The prognosis is grave for patients with HBV-related decompensated liver cirrhosis (LC). We evaluated the effectiveness and the determinants of early mortality of lamivudine treatment in patients with HBV-related decompensated LC. Thirty patients with HBV-related decompensated LC and active viral replication were treated with lamivudine 100 mg daily for a median duration of 9 months. Among these patients, five patients died within 3 months. Two patients were lost to follow-up at week 8 and 9. One patient was treated for <6 months. Twenty-two patients were treated over 6 months. Univariate analysis revealed that the total bilirubin (P = 0.008), prothrombin time (P = 0.004), Child-Turcotte-Pugh score (P = 0.005), the model of efd-stage liver disease score (P = 0.004) and stage III hepatic encephalopathy (P = 0.001) were predictive factors of early mortality. Multivariate analysis revealed that the independent factor associated with early mortality was stage III encephalopathy. Among 22 patients, liver function improved markedly after lamivudine therapy. Of the nine hepatitis B e antigen (HBeAg)-positive patients, three had HBeAg seroconversion. Two patients had YMDD mutant and virological breakthrough at 41 and 46 weeks. One of the two had hepatocellular carcinoma and died of hepatic failure at week 125; the other received adefovir and is doing well. Lamivudine appeared to have benefits in viral suppression and significant improvement in liver function in patients with HBV-related decompensated LC. As noted in prior studies, poor baseline liver function is associated with a poor prognosis in Asian patients with decompensated HBV cirrhosis treated with lamivudine.     

Adefovir dipivoxil added to ongoing lamivudine in chronic hepatitis B with YMDD mutant hepatitis B virus

BACKGROUND AND AIMS: Prolonged lamivudine therapy is associated with treatment-resistant YMDD mutant hepatitis B virus (HBV). We evaluated the efficacy and safety of adding adefovir dipivoxil to lamivudine in 135 patients with chronic hepatitis B (CHB) and YMDD mutant HBV. METHODS: Ninety-five patients with compensated CHB (group A) were randomized to adefovir 10 mg daily (n = 46) or placebo (n = 49) for 52 weeks while continuing treatment with lamivudine. Forty patients with decompensated hepatitis B or post-liver transplantation (group B) received adefovir and lamivudine. The primary end point was a decline in serum HBV DNA level to 10(5) copies/mL or a >2 log(10) reduction from baseline at weeks 48 and 52. RESULTS: HBV DNA response occurred in 85% of patients (39 of 46) in group A given combined therapy versus 11% (5 of 46) receiving lamivudine alone (P < 0.001), with a significant change in HBV DNA level from baseline (P < 0.001) between treatment groups (median, -4.6 vs. +0.3 log(10) copies/mL, respectively). Normalization of alanine aminotransferase levels occurred in 31% of patients (14 of 45) receiving combined therapy versus 6% (3 of 48) receiving lamivudine alone (P = 0.002). Ninety-two percent of patients (36 of 39) in group B had an HBV DNA response (median change of -4.6 log(10) copies/mL) and improved liver chemistries (P < or = 0.001). Both treatment regimens were well tolerated, and renal function abnormalities were not observed in either group. CONCLUSIONS: The addition of adefovir dipivoxil to lamivudine in patients with CHB with compensated or decompensated liver disease due to YMDD mutant HBV is associated with virologic and biochemical improvement during 52 weeks of treatment and is well tolerated.     

拉米夫定、阿德福韦酯联合自体骨髓干细胞移植治疗乙肝肝硬化失代偿期患者的疗效观察

目的观察拉米夫定、阿德福韦酯联合自体骨髓干细胞移植治疗乙肝肝硬化失代偿期患者的临床效果。方法77例乙肝肝硬化失代偿期患者随机分为两组。常规对症支持治疗方法下,A组（37例）采用拉米夫定、阿德福韦酯抗病毒治疗,B组（40例）在A组基础上加用自体骨髓干细胞移植治疗。治疗4周后复查各实验室指标、l临床症状和体征情况。结果治疗4周后,B组血浆白蛋白、天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、总胆红素水平、PT、AFP、胆碱酯酶等指标较A组明显改善（P〈0．05）;B组临床症状和体征较A组也明显改善（P〈0．05）。结论采用拉米夫定、阿德福韦酯联合自体骨髓干细胞移植治疗乙肝肝硬化失代偿期患者,可有效避免骨髓干细胞受到患者体内乙肝病毒的感染和损害,帮助骨髓干细胞在肝脏环境内能分化为正常的肝细胞,参与肝脏结构的修复和重构,改善患者的肝功能,提高患者的生活质量。     

Decompensated lamivudine-resistant hepatitis B virus-related cirrhosis treated successfully with adefovir dipivoxil allowing surgery for hepatocellular carcinoma

We describe a 64-year-old man with decompensated hepatitis B virus (HBV)-related cirrhosis who became resistant to lamivudine. He was started on adefovir at 10 mg daily while continuing lamivudine therapy. Several months later, his liver function improved and subsequently his ascites disappeared. The serum HBV-DNA level became undetectable 11 months later. Twenty months after the start of additional treatment with adefovir, one hepatocellular carcinoma (HCC) was detected, and the patient underwent a successful hepatectomy. Our findings suggest that the addition of adefovir to ongoing lamivudine therapy is useful for improving liver function in patients with decompensated lamivudine-resistant HBV-related cirrhosis, allowing surgery for HCC.     

Lamivudine treatment for decompensated cirrhosis resulting from chronic hepatitis B

The prognosis of decompensated cirrhosis resulting from chronic hepatitis B is poor, and the benefits of treatment with interferon are outweighed by serious side effects and by the risk of fatal exacerbation of disease activity. Lamivudine rapidly reduces hepatitis B virus (HBV)-DNA in serum to undetectable levels. We have treated 35 patients with chronic hepatitis B and decompensated cirrhosis with lamivudine 100 mg or 150 mg orally once daily. Pretreatment, all were positive for HBV-DNA in serum. Ten had Child-Pugh class B and 25 had Child-Pugh class C liver disease. Seven patients underwent liver transplantation within 6 months of treatment initiation, 5 patients died within 6 months, and 23 patients were treated for at least 6 months (mean = 19 months). In a majority of these 23 cases, there was a slow but marked improvement in liver function, which was most apparent after 9 months of treatment, with a decrease in serum bilirubin from 67 +/- 13 to 30 +/- 4 micromol/L (P <.05, baseline vs. 9 months), an increase in serum albumin from 27 +/- 1 to 34 +/- 1g/L (P <.05), and a decrease in Child-Pugh score from 10.3 +/- 0.4 to 7.5 +/- 0.5 (P <.05). Three patients developed resistance to lamivudine because of a mutation in the YMDD motif, but liver function did not deteriorate. We conclude that inhibition of viral replication with lamivudine results in a significant improvement of liver function in patients with decompensated HBV cirrhosis, but the long-term benefits remain uncertain.     

乙型肝炎肝硬化失代偿期初始拉米夫定和阿德福韦酯联合抗病毒治疗的疗效观察

目的研究拉米夫定（LAM）初始联合阿德福韦酯（ADV）治疗乙型肝炎肝硬化失代偿期患者的疗效与安全性。方法30例HBeAg阳性乙型肝炎肝硬化失代偿期患者,分为LAM初始联合ADV治疗组和变异后联合组,疗程均为48周。结果初始联合组与变异后联合组患者ALT与TBil在治疗4、12、24与48周均较基线明显好转（P〈0．05）,治疗4、12周后,两组均无HBVDNA转阴的患者,治疗24周后,分别有4例（40％）初始联合组与4例（20％）变异后联合组患者HBVDNA转阴,但差异无统计学意义。治疗48周后,初始联合组与变异后联合组HBVDNA转阴率分别为90％（9／10）与40％（8／20）,HBeAg／抗-HBe血清转换率分别为60％（6／10）与20％（4／20）,两组间差异均具有统计学意义（P〈0．05）。初始联合组患者Child—Pugh评分在48周时,优于变异后联合组（P〈0．05）。结论ADV初始联合LAM治疗在改善乙型肝炎肝硬化失代偿期患者临床状况及抗病毒方面均明显优于变异后联合治疗。     

恩替卡韦治疗乙型肝炎肝硬化失代偿期的Meta分析

目的比较恩替卡韦、拉米夫定、阿德福韦酯治疗乙型肝炎肝硬化失代偿期的疗效。方法计算机检索PubMed、MEDLINE、EBSCO、CNKI、万方数据库、重庆维普等,并追查所有纳入的参考文献。检索年限均从建库到2013年3月。纳入恩替卡韦与拉米夫定或阿德福韦酯比较治疗乙型肝炎肝硬化失代偿期的随机对照试验。采用Jadad评分法评价纳入研究的方法学质量,并用Cochrane协作网提供的RevMan 5.0软件进行Meta分析,并对不同疗程进行亚组分析。结果纳入8个随机对照试验(n=708),Meta分析结果显示:恩替卡韦治疗乙型肝炎肝硬化失代偿期24周HBV DNA转阴率略高于拉米夫定组,差异无统计学意义(P0.05),但明显高于阿德福韦酯组,差异有统计学意义(P0.00001);48周恩替卡韦组HBV DNA转阴率明显高于拉米夫定组和阿德福韦酯组,差异有统计学意义(P0.00001)。48周恩替卡韦组HBeAg血清转换率与拉米夫定组和阿德福韦酯组差异无统计学意义(P0.05)。结论长期的恩替卡韦治疗乙型肝炎肝硬化失代偿期疗效明显优于拉米夫定和阿德福韦酯。     

Lamivudine treatment of decompensated hepatitis B virus-related cirrhosis

BACKGROUND: Patients with decompensated hepatitis B vires (HBV)-related cirrhosis tend to have low or undetectable HBV replication. However, some patients continue to have high levels of HBV replication and effective suppression of HBV replication with antiviral agents may potentially decrease hepatic necroinflammation and improve or stabilize liver function. This review was to under stand the efficacy and safety of lamivudine in the treatment of decompensated HBV cirrhosis. DATA SOURCES: An English-language literature search (MEDLINE January 1988-July 2005) was performed, and a total of 52 articles/abstracts relevant to the issue were selected. After review of the selected papers, the meaningful results and conclusions were extracted using scientific crite ria. The papers reviewed pertained mainly to the efficacy and safety profiles of lamivudine treatment for decompensated HBV cirrhosis. RESULTS: The ultimate treatment of decompensated HBV cirrhosis is liver transplantation, but lamivudine treatment may lead to rapid suppression of viral replication and improvement of biochemical and clinical parameters, reduced morbidity and hospitalization for complications of liver disease, increased pre-transplant survival as well as reduced need for transplantation. However, viral resistance can develop after prolonged treatment with lamivudine, and breakthrough hepatitis may be fatal in few patients. Adefovir is effective for lamivudine-resistant HBV mutants. CONCLUSIONS: Antiviral therapy with lamivudine for decompensated HBV cirrhosis can be effective. However, some patients may experience a hepatitis flare with the emergence of YMDD mutants resulting in progressive worsening of liver disease, and should be referred for "rescue" therapy with other nucleoside/nucleotide analogues such as adefovir dipivoxil.