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1.
Hepatitis B virus (HBV) recurrence and de novo HBV infection are frequent events in liver transplantation recipients. Treatment with lamivudine is initially efficient in both infections but the incidence of lamivudine-resistant HBV emergence increases over time. Adefovir appears to be promising in post-liver transplantation patients with recurrent HBV infection and lamivudine-resistant HBV. This study analyzed adefovir treatment in 42 post-liver transplantation patients who developed recurrent HBV or de novo HBV infection with lamivudine-resistant HBV (54.8% HCV-coinfected). Patients received 10 mg of oral adefovir once daily for a mean period of time of 21.5 months (range from 12 to 31 months). In 62.9% of patients, ALT levels decreased significantly. Serum HBV-DNA was undetectable in 64% of the cases. Twenty percent of patients lost HBeAg marker and 13.3% of them developed anti-HBe. In 9.5% of recipients, HBsAg became negative. There was no significant change in serum creatinine levels. In only one patient was worsening of the renal function detected, making dose adjustment necessary. No other side effects were reported. Our results confirm the efficacy and safety of adefovir treatment in post-liver transplantation patients with lamivudine-resistant HBV, neither were adefovir-resistant mutations identified in patients after 21 months of therapy, nor were there adverse events, especially renal toxicity.  相似文献   

2.
We report the treatment outcome in six post-renal transplant patients with lamivudine-resistant hepatitis B virus (LR-HBV) infection using adefovir dipivoxil and followed for 6 to 18 months. Posttransplant immunosuppressive therapy was not altered. Adefovir dipivoxil effectively suppressed hepatitis B virus DNA and improved alanine transferase, although DNA suppression seemed dependent on continued therapy. Nephrotoxicity led to withdrawal of the drug in three patients. This may limit therapeutic usefulness in a significant proportion of post-renal transplant patients with LR-HBV infection.  相似文献   

3.
Lamivudine is a safe, effective treatment for hepatitis B virus (HBV) reactivation after renal transplantation. However, prolonged lamivudine therapy can produce resistance to the drug. Adefovir dipivoxil (ADV) has demonstrated efficacy in patients with lamivudine resistance, but there is limited clinical experience in patients with either renal transplants or severe renal insufficiency. A 47-year-old man with asymptomatic HBV infection underwent renal transplantation in November 1995. In September 2000 lamivudine therapy was initiated to treat HBV reactivation. The outcome was good, with negative HBV DNA levels. Two years later, significant viral replication developed again. At that time the patient already had advanced renal insufficiency due to chronic graft nephropathy. The transaminase levels were increased, and the HBV DNA reached greater than 200,000 copies/mL by polymerase chain reaction, with development of ascites and cirrhosis. The patient was started on ADV 10 mg every 72 hours (dose adjusted to renal function). There was rapid normalization of hepatic enzymes and progressive decline of the viral load. HBV DNA became negative after 6 months of ADV treatment. The renal function has since remained stable. This case suggests that ADV can be safe and effective in the treatment of renal transplant patients with lamivudine-resistant hepatitis B, even in the presence of advanced renal insufficiency.  相似文献   

4.
目的比较两种阿德福韦酯治疗慢性乙型肝炎的成本-效果分析。方法将248例慢性乙型肝炎(CHB)患者分为进口阿德福韦酯(商品名:贺维力Hepsera,葛兰素史克制药公司)组和国产阿德福韦酯(商品名:阿甘定AGD,福建广生堂药业有限公司)组,观察临床疗效并作成本-效果分析。结果贺维力^R组和阿甘定^R组总有效率分别为91.1%、89.7%(P〉0.05),成本-效果比分别为189.8、86.6(P〈0.05)。结论国产阿德福韦酯可作为治疗的较佳方案。  相似文献   

5.
Lamivudine treatment in patients with chronic hepatitis B virus (HBV) infection may improve clinical state and suppress viral replication before liver transplantation. Emergence of lamivudine-resistant YMDD mutant is common. We report the results of liver transplantation in 16 patients with pretransplantation YMDD mutants after receiving lamivudine treatment for a median of 738 days (range, 400-1799 days). Adefovir dipivoxil (10 mg daily) was added on to lamivudine for a median of 20 days (range, 8-271 days) before (n = 11) or at (n = 5) liver transplantation, and the combination was continued indefinitely thereafter. Eight patients received additional intravenous hepatitis B immune globulin (HBIG) for a median of 24 months. Fifteen patients with known pre-adefovir HBV DNA levels had a median titer of 14,200 x 10(3) copies/mL (2 x 10(3) to 4,690,000 x 10(3) copies/mL), and 14 had HBV DNA >10(5) copies/mL. All but 1 patient remained positive for HBV DNA (by quantitative polymerase chain reaction [qPCR]) at the time of liver transplantation, and the titer was greater than10(5) copies/mL in 8 patients. The median follow-up after liver transplantation was 21.1 (range, 4.4-68.9) months. One patient (6%) died of an unrelated cause 12.2 months after transplantation, and 15 patients (94%) were alive with the original graft. All patients cleared HBV DNA and had no detectable HBV DNA by qPCR at the latest follow-up. Fourteen patients had cleared hepatitis B surface antigen (HBsAg), but 2 patients who received only adefovir dipivoxil and lamivudine without HBIG remained HBsAg positive after 7.7 and 9.5 months. Serum HBV DNA, however, was negative, and there was no biochemical or histological evidence of recurrence. Adefovir dipivoxil was well tolerated with no significant renal toxicity. In conclusion, a combination of add-on adefovir dipivoxil plus lamivudine therapy provides effective prophylaxis in patients with pretransplantation YMDD mutant that may be actively replicating. The cost effectiveness of additional passive immunoprophylaxis remains to be defined.  相似文献   

6.
阿德福韦酯是抑制HBV的核苷(酸)类似物,目前已证明能有效降低HBV DNA载量,促进ALT复常和HBeAg血清学转换,改善肝脏组织学,且与其他核苷(酸)类似物无明显交叉耐药,因此广泛应用于慢性乙型肝炎和乙型肝炎肝硬化患者[1].  相似文献   

7.
Background. Adefovir (ADV), an orally administered nucleotideanalogue active against hepadnaviruses, retroviruses and herpesviruses was shown to be effective in HIV-infected patients,but the prevalence of nephrotoxicity with doses of 60–120mg/day was considered unacceptable. Recently, lower doses ofADV were shown to be effective for the treatment of HIV-1 patientswith chronic lamivudine (LAM)-resistant hepatitis B. Methods. In a cohort of 35 patients infected with both HIV-1and LAM-resistant hepatitis B virus, we investigated the renaltolerance of a once-daily dose of ADV 10 mg over 52 weeks. Theirmean baseline creatinine clearance was within the normal range(105 ± 3 ml/min/1.73 m2). No patient had significantchanges in renal function or electrolyte balance secondary toADV treatment. Results. Transient increases in serum creatinine, which resolvedby the end of the study were noted in two patients and threedeveloped proteinuria, which was felt to be unrelated to ADVtreatment. The cohort's mean serum phosphate level, 2.45 ±0.09 mg/dl at baseline, did not change significantly under treatment(2.66 ± 0.12 mg/dl at week 52, P = NS). Conclusions. Our study shows that ADV dosed at 10 mg/day forthe treatment of LAM-resistant chronic hepatitis B in patientsco-infected with HIV is not associated with renal tubular dysfunctionor a significant change in renal function.  相似文献   

8.
目的分析阿德福韦酯(ADV)疗效欠佳的影响因素,并初步探讨对具有ADV疗效欠佳高危因素的患者进行优化治疗的疗效。方法 ADV治疗48周时HBVDNA≥103拷贝/ml定义为ADV疗效欠佳。对147例门诊服用ADV患者的临床资料进行随访统计。对可能影响ADV疗效的因素进行非条件Logis-tic单因素和多因素模型分析,对具有ADV疗效欠佳高危因素的患者根据是否进行优化治疗进行分层分析,以HBVDNA低于检测下限的比率为观测指标,使用乘积限法(Kaplan-Meier)进行分析,然后采用时序检验Log-rank法进行比较。结果 Logistic回归分析结果发现,YMDD变异与否(OR:7.888,95%CI:2.302~27.031,P=0.001)、基线HBeAg状态(OR:6.001,95%CI:2.080~17.306,P=0.001)、基线HBVDNA水平(OR:1.635,95%CI:1.007~2.655,P=0.047)、对ADV是否发生原发无应答(OR:15.214,95%CI:1.800~128.609,P=0.012)、初始病毒学应答(OR:0.172,95%CI:0.057~0.517,P=0.002)为ADV疗效欠佳的5个独立影响因素,且YMDD变异阳性、基线HBeAg阳性、基线HBVDNA水平越高、对ADV发生原发无应答及未发生初始病毒学应答的患者越易发生ADV疗效欠佳。本研究中优化治疗组的HBVDNA低于检测下限的比率显著高于未优化治疗组。结论 YMDD变异阳性、基线HBeAg阳性、基线HBVDNA水平高、对ADV发生原发无应答及未发生初始病毒学应答是发生ADV疗效欠佳的高危因素,具有上述5个发生ADV疗效欠佳高危因素的患者可能从优化治疗中获益。  相似文献   

9.
目的探讨基线血清TNFα、ALT、HBVDNA载量及24周HBV血清学标志物等因素对阿德福韦酯(ADV)治疗HBeAg阳性慢性乙型肝炎(CHB)48周时患者血清学应答的预测价值。方法203例HBeAg阳性CHB患者口服ADV治疗48周,10mg/d。采用ELISA测定HBV血清学标志物和基线血清TNFα水平,荧光定量PCR检测HBVDNA,Logistic回归分析影响HBeAg阳性患者血清学应答的因素。结果203例患者治疗24周时HBV DNA转阴率为31.5%(64/203),ALT复常率为59.1%(120/203),HBeAg转阴率为15.8%(32/203),HBeAg转换率为8.9%(18/203),应答率为13.3%(27/203);治疗48周时HBV DNA转阴率为58.6%(119/203),ALT复常率为78.3%(159/203),HBeAg转阴率29.6%为(60/203),HBeAg转换率为16.7%(34/203),应答率为25.6%(52/203)。Logistic回归分析发现,48周HBeAg转阴的患者较未转阴者的24周HBV DNA转阴率、HBeAg转阴率及转换率、基线TNFα水平高(P值分别为0.017、0.001、0.029和0.040);48周HBeAg转换的患者较未转换者的24周HBeAg转换率高,而基线HBVDNA低(P值分别为0.000和0.004)。结论24周HBVDNA转阴率、HBeAg转阴率和转换率,及基线TNFα水平可以预测48周HBeAg转阴率,而24周HBeAg转换率和基线HBV DNA载量可以预测48周HBeAg转换率。  相似文献   

10.
目的 观察拉米夫定和(或)阿德福韦酯治疗失代偿期乙型肝炎肝硬化3年疗效.方法 收集乙型肝炎肝硬化失代偿期患者68例,分为抗病毒治疗组和对照组,观察入组患者的临床症状、体征、生化指标、HBV DNA和Child-Pugh分级等变化情况.结果 随访治疗中,治疗组6个月后ALT、ALB和HBV DNA水平均较对照组有明显改善,12个月后TBil和Child-Pugh评分较对照组有明显改善,差异具有统计学意义(P<0.05);治疗组和对照组36个月生存率分别为62.5%和36.1%,差异具有统计学意义(P< 0.05);36个月后治疗组和对照组肝细胞癌发生率分别为3.1%和8.3%,差异无统计学意义.结论 拉米夫定和(或)阿德福韦酯治疗失代偿期乙型肝炎肝硬化,能够改善患者肝功能,延缓疾病进展,提高生存率.  相似文献   

11.
目的探讨阿德福韦酯耐药慢性乙型肝炎患者相关S抗原变异、疫苗逃逸相关变异以及部分已知特异性T细胞表位变异情况。 方法收集2007年12月至2011年9月于首都医科大学附属北京地坛医院收治的阿德福韦酯治疗失败的慢性乙型肝炎患者70例,并随机选择ADV治疗非耐药患者70例作为对照。采用PCR产物直接测序法获得患者HBV反转录酶区与S抗原序列。应用PCR产物直接测序法与焦磷酸测序法明确阿德福韦酯耐药情况。比较阿德福韦酯耐药患者与无阿德福韦酯耐药患者耐药相关S抗原变异、疫苗逃逸相关变异以及HBV特异性T细胞表位变异情况。 结果ADV耐药组与对照组患者人口学等指标差异无统计学意义。本组患者中42例rtA181T耐药变异关联的HBsAg变异均为sW172*。在rtA181T/ sW172*变异患者体内,该变异株在病毒准种中所占平均比率为(42.6 ± 22.1)%(12.2%~100%)。与非ADV耐药组患者相比,ADV耐药组患者发生HBsAg疫苗逃逸变异(χ2 = 12.8736、P = 0.0003)以及T细胞抗原表位变异(χ2 = 4.8344、P = 0.0279)几率显著升高。 结论我国ADV耐药患者rtA181T变异关联的HBsAg变异主要为sW172*变异,HBsAg抗原疫苗逃逸变异以及T细胞抗原表位变异与ADV耐药相互影响,相关机制尚待进一步研究。  相似文献   

12.
目的评价阿德福韦酯治疗HBeAg阳性的慢性乙型肝炎(CHB)患者的疗效。方法58例核苷(酸)类似物初治的HBeAg阳性的慢性乙型肝炎患者,随机分为阿德福韦酯组(10mg/d)36例和安慰剂组22例,分别接受12周治疗后,所有患者均进入为期36周的开放用药(阿德福韦酯10ms/d)阶段。观察患者血清HBVDNA水平、HBeAg和肝脏生物化学功能的变化。结果经过12周的治疗,阿德福韦酯组患者的血清HBVDNA平均下降3.17 log10拷贝/ml,降幅显著高于服用安慰剂组的0.79 log10拷贝/ml(P〈0.05)。第12周和48周时,两组患者的ALT复常率、HBeAg阴转率和HBeAb血清转换率均无明显差异。在治疗结束时,有5例患者出现了HBVDNA反弹,其中1例患者发生了与阿德福韦酯耐药相关的变异。结论(1)阿德福韦酯(10mg/d)治疗HBeAg阳性的慢性乙型肝炎患者具有良好的抗病毒和临床疗效;(2)在48周疗程中,5例(8.8%)患者出现HBVDNA反弹,其中1例为耐药突变,其余4例未检测到相关耐药突变;(3)阿德福韦酯治疗48周,相关耐药突变的发生率为1.7%。  相似文献   

13.
目的观察阿德福韦酯对拉米夫定治疗过程中出现YMDD变异的乙型肝炎失代偿期肝硬化的疗效和安全性。方法将60例在拉米夫定治疗过程中出现YMDD变异的乙型肝炎失代偿期肝硬化患者随机分为治疗组(30例)和对照组(30例),两组均在保肝、利胆等常规内科综合治疗基础上继续接受拉米夫定100mg/d口服治疗,治疗组在上述基础上联合阿德福韦酯10mg/d口服,疗程为15个月。结果对照组1例出现肝细胞癌死亡,3例因并发上消化道大出血死亡,1例因并发肺部真菌感染而给予抗真菌治疗后导致肝功能衰竭死亡,1例因合并腹腔感染未能很好控制导致肝功能衰竭死亡。治疗15个月时结果显示,治疗组肝功能恢复情况及HBVDNA低于检测下限的比率均优于对照组(P〈0.01),治疗组病死率为O%,对照组为23.3%。结论阿德福韦酯治疗YMDD变异的乙型肝炎失代偿期肝硬化患者有良好的疗效和安全性,能提高患者生存质量,改善预后。  相似文献   

14.
BACKGROUND: The incidence of adefovir dipivoxil (ADV) nephrotoxicity has been previously reported with the 60 and 120 mg daily dose in human immunodeficiency virus (HIV). We report a complete analysis on the renal tolerance of ADV at the currently approved dose of 10 mg daily for the treatment of chronic hepatitis B. METHODS: To investigate the efficacy, safety, and the tolerability of two dosing regimens of ADV (10 mg daily or 30 mg daily), two double-blind, placebo-controlled studies were performed in patients with chronic hepatitis B and compensated liver disease who were not undergoing current treatment and who had evidence of hepatitis B virus (HBV) replication. RESULTS: There was no overall median change from baseline at week 48 in serum creatinine or serum phosphorus levels in the ADV 10 mg group. In the ADV 30 mg group there was a slight increase of 0.2 mg/dL in median serum creatinine levels, and decrease of 0.1 mg/dL in serum phosphorus levels at week 48. Serum creatinine increase and hypophosphatemia were more frequently observed in patients receiving ADV 30 mg daily compared with ADV 10 mg and placebo. There were no grade 4 proteinuria, hematuria, or glycosuria events. CONCLUSION: Mild nephrotoxicity was demonstrated with the dose of 30 mg daily. Nephrotoxicity, as defined by an increase >/=0.5 mg/dL from baseline in serum creatinine or a serum phosphorus value of <1.5 mg/dL on two consecutive occasions, was not observed in patients treated with ADV 10 mg for a median follow-up period of approximately 64 weeks.  相似文献   

15.
目的:进一步探讨阿德福韦酯(ADV)所致低磷性骨软化症的临床特点。方法回顾性分析2010至2012年共收治的8例慢性乙型肝炎患者经ADV治疗所致低磷性骨软化症的临床表现、治疗和转归。结果8例患者均在服用ADV后出现低磷血症及骨质疏松,其主要临床表现为乏力、多发骨痛,进行加重至行走障碍;低血磷、低尿酸和高碱性磷酸酶血症、骨密度检查提示骨质疏松。经停用ADV、对症补钙、补磷治疗后患者的血磷恢复正常,疼痛缓解,骨质疏松改善。结论 ADV可引起低磷性骨软化症;补充磷、维生素D3及钙剂治疗可恢复。  相似文献   

16.
目的观察乙型肝炎肝硬化并脾功能亢进患者行脾部分栓塞术后阿德福韦酯疗效。方法41例乙型肝炎肝硬化并脾功能亢进患者行脾部分栓塞术治疗后,21例口服阿德福韦酯10mg/d,疗程1年,对照组20例常规护肝、降酶等对症治疗。观察两组患者肝功能、血清肝纤维化指标、HBVDNA、HBeAg/抗.HBe血清学变化、Child-Pugh分级比较和不良反应。结果治疗组ALT、AST、TBil、ALB各项指标优于对照组,血清肝纤维化HA、PC-Ⅲ、Ⅳ—C各项优于对照组,治疗组HBVDNA转阴11例,对照组转阴1例,差异有统计学意义(Χ^2=8.5,P〈0.05)。治疗组发生HBeAg/抗.HBe血清转换者4例,对照组1例,差异有统计学意义(Χ^2=3.2,P〈0.05)。治疗组Child.Pugh分级为A级者9例,B级10例,C级2例;对照组A级6例,B级7例,C级7例,差异有统计学意义(Χ^2=5.9,P〈0.05)。阿德福韦酯治疗组未发现相关的肾功能损害和其他不良反应。结论乙型肝炎肝硬化并脾功能亢进患者行脾部分栓塞术治疗,脾功能亢进可获得明显改善,但不能阻止乙型肝炎肝硬化病情进展,脾栓塞术后采用阿德福韦酯是较理想的长期抗病毒药物。  相似文献   

17.
18.
目的探讨阿德福韦酯对慢性乙型肝炎患者血清HBVCCCDNA的影响。方法40例慢性乙型肝炎患者,按1:1随机分配接受阿德福韦酯或安慰剂治疗,所有患者均治疗52周并在停药后随访52周;应用实时荧光定量聚合酶链反应技术检测慢性乙型肝炎患者0周、26周、52周、78周、104周血清HBVCCCDNA及HBVDNA含量。结果治疗组20例患者治疗前(0周)血清HBVCCCDNA中位数水平为8.29×10^6拷贝/ml(与对照组相比P〉0.05);接受阿德福韦酯治疗半年(26周)及1年(52周)血清HBVCCCDNA中位数水平分别为2.61×10^4拷贝/ml、7.78×10^3拷贝/ml(与治疗前相比两者P〈0.05),停药半年(78周)及1年(104周)血清HBVCCCDNA中位数水平分别为3.38×10^4拷贝/ml、3.60×10^4拷贝/ml(与治疗前相比两者P〈0.05);接受阿德福韦酯治疗半年及1年血清HBVCCCDNA分别下降2.502log10、3.028log10(与对照组相比两者P〈0.05),停药半年及1年血清HBVCCCDNA较停药时上升0.638log10、0.665log10(与对照组相比两者P〈0.05)。结论阿德福韦酯对血清HBVCCCDNA有明显抑制作用;血清HBVCCCDNA可作为阿德福韦酯抗病毒治疗的重要监测指标。  相似文献   

19.
Current therapies for the treatment of chronic hepatitis B virus (HBV) infection do not eliminate viral replication once therapy is stopped, resulting in a rapid rebound of viremia in a majority of patients. Prolonged therapy results in emergence of resistant virus, which is a major clinical concern. The appearance of resistant HBV is associated with decreased seroconversion rates as well as worse liver histology. Adefovir dipivoxil, a nucleotide analogue with potent antiviral activity against HBV and human immunodeficiency virus (HIV), has shown in vivo and in vitro to have activity against lamivudine-resistant HBV. We present a series of 6 patients with chronic HBV infection and lamivudine-resistant HBV treated with adefovir dipivoxil. The viremia decreased in all patients; in 4 of them, serum HBV DNA was negative by chain reaction (PCR) in a mean period of 10 months from beginning of treatment. Resistance to adefovir after 12 months of treatment has not been detected. Alanine aminotransferase (ALT) levels decreased in all patients and, at this moment, 5 of 6 patients present normal levels. There were no toxic side effects due to adefovir treatment. The data confirm that adefovir treatment has efficacy against HBV lamivudine-resistant forms.  相似文献   

20.
INTRODUCTION: Complications of hepatitis B virus (HBV) infection are among the most common indications for liver transplant in many parts of Asia. However, none of the current posttransplant hepatitis B prophylaxis strategies, namely, lamivudine, hepatitis B immunoglobulin monotherapy, or combination therapy, is ideal. Our aim was to evaluate the use of adefovir dipivoxil (ADV) as a rescue therapy for posttransplant HBV patients who developed lamivudine resistance. METHODS: Twenty-two consecutive patients with HBV-related liver disease, who underwent first liver transplants from 1995 to 2002, received HBV prophylaxis with indefinite lamivudine with substitution of ADV for patients who developed drug resistance and clinical deterioration, defined as persistent elevation of transaminases or histologic deterioration. RESULTS: Sixteen patients (73%) were alive at their last follow-up and six (38%) had developed hepatitis B recurrence at a median of 46 (range 9 to 74) months posttransplant. Two with persistently normal transaminases and normal liver histology at 3 and 42 months postrecurrence have been continued on lamivudine. Four showed clinical deterioration and received ADV for a median of 24 months; all displayed normalization of transaminases and a 2 to 5 log drop in HBV DNA titers. Three had paired biopsies before and after substitution of ADV with two showing improvement and one stable appearance. The median serum creatinine value increased slightly from 126 to 138 micromol/L (P = 0.72). CONCLUSION: ADV is an effective rescue therapy for patients with lamivudine-resistant hepatitis B post-liver transplant. Further studies are needed to ascertain the optimal posttransplant hepatitis B prophylaxis.  相似文献   

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