阿德福韦酯治疗YMDD变异慢性乙型肝炎82例

目的:研究阿德福韦酯治疗YMDD突变后慢性乙型肝炎患者的疗效和安全性。方法:82例YMDD突变的慢性乙型肝炎患者分为对照组和试验组,对照组服用拉米夫定100mg·d-1,48周,试验组服用阿德福韦酯10mg·d-1,48周。服药后第24,48周检测谷丙转氨酶(ALT)、HBV DNA定量、HBeAg及观察不良反应。结果:试验组24及48周HBV DNA下降水平均明显高于对照组(均P<0·01),HBV DNA应答率和ALT复常率也均高于对照组(均P<0·01),HBeAg阴转率两组无显著性统计学差异。两组均未发现明显不良反应。结论:阿德福韦酯治疗YMDD突变的慢性乙型肝炎安全有效。     

乙型肝炎病毒基因型与阿德福韦酯治疗效应的关系

目的:探讨乙型肝炎病毒基因型与阿德福韦酯治疗效应的关系。方法:采用聚合酶链式反应(PCR)结合TaqmanMGB探针技术,对血清中HBV基因型进行分型检测,观察63例不同基因型慢性乙型病毒性肝炎患者经阿德福韦酯(商品名:贺维力)治疗后ALT水平、HBVDNA定量、HBeAg血清转换情况。结果:63例HBV患者中B基因型17例(27.0%),C基因型46例(73.0%)。阿德福韦酯治疗3个月与治疗12个月时B基因型与C基因型两组间ALT、HBVDNA水平差异无显著性意义(P>0.05)。而治疗6、9个月后,两组ALT、HBVDNA水平差异有显著性意义(P<0.01),阿德福韦酯对B基因型疗效优于C型;治疗12个月,B、C基因型HBeAg血清转换率差异有显著性意义(P<0.05)。结论:短期观察HBV基因型与阿德福韦酯的治疗效应存在一定的相关性,HBV基因B型患者HBeAg血清转换率高于C型患者。     

阿德福韦酯片治疗慢性乙型肝炎的临床研究

目的:评价阿德福韦酯片对慢性乙型肝炎患者的临床疗效及安全性。方法:采用随机、双盲、安慰剂平行对照、多中心临床试验,试验分两个阶段,持续48周。将病人随机分为阿德福韦酯组(A组)和安慰剂组(B组),第一阶段A组服用阿德福韦酯片10mg,每日1次。B组服用安慰剂,每日1次,双盲治疗12周;第二阶段A组和B组都服用阿德福韦酯片10mg,每日1次,开放治疗36周。分别在治疗的4、8、12、24、36、48周末进行疗效和安全性评价。结果:两组治疗至12周,血清HBV-DNA水平(对数值)分别下降2.27、0.48,较基线水平相比两组差异有统计学意义(P<0.05),即阿德福韦酯与安慰剂相比,可显著降低HBV-DNA水平。治疗至48周时,两组可使血清HBV-DNA(对数值)的含量较基线时分别下降3.30和3.40,两组数值较基线数值差异有统计学意义(P<0.05);分别有73.89%和74.68%的患者血清HBV-DNA的含量较基线时下降≥21og10,两组数值较基线数值差异无统计学意义(P≥0.05)。结论:阿德福韦酯片抑制乙肝病毒复制安全有效,是可以治疗慢性乙型肝炎的药物。     

Treatment of chronic hepatitis B

In the last years, marked progress has been made in the treatment of chronic hepatitis B. The efficacy of lamivudine, the first nucleoside analogue available, is limited by the high incidence of resistance. Adefovir, which was recently approved has a comparable efficacy with a very low frequency of resistance. However, adefovir needs to be indefinitely administered as withdrawal of therapy is generally associated with reactivation and sustained response is uncommon. Recent large randomized controlled trials showed that PEG IFNs induce relatively high sustained response rates both in HBeAg positive and HBeAg negative chronic hepatitis B. So far, the combination of PEG IFN with lamivudine, used simultaneously, is disappointing in terms of short-term efficacy. However, long-term efficacy needs to be assessed and different schedules of combination (for example sequential) need to be evaluated. A number of nucleoside analogues, with favourable toxicity profiles and a promise of increased effectiveness against HBV, are at various stages of clinical development. Results of phase III trials of entecavir and emtricitabine confirmed their efficacy. However, while entecavir is associated with a low incidences of resistance, emtricitabine is associated with a relatively high incidence of resistance which limits its use as a monotherapy. The efficacy and safety of new and more potent drugs like telbivudine and clevudine need to be confirmed. The future of chronic hepatitis B therapy seems to be in the combination of different drugs. Ideally, the optimal drugs to combine would meet the following criteria: they should have different sites of action on HBV DNA replication, a potent antiviral effect, an excellent safety profile and they should induce a sustained response with a limited duration of therapy. Indeed, the concept of combination therapy has been recently developed in order to increase efficacy and to decrease the occurrence of viral resistance. However, so far few combinations have been evaluated. No combination therapy demonstrated a benefit as compared with monotherapy. More potent drugs and new combinations together with the understanding of the mechanisms of resistance to therapy are important challenges to improve the efficacy of treatment and decrease in the future the global burden related to chronic hepatitis B.     

复方灵芝汤联合阿德福韦酯治疗HBeAg阳性慢性乙型肝炎临床研究

目的：观察复方灵芝汤联合阿德福韦酯治疗病毒性肝炎的临床疗效。方法：将108例慢性乙型病毒性肝炎患者随机分为两组,对照组单纯采用阿德福韦酯胶囊10 mg口服,1次/d,疗程2 a。观察组在对照组基础上加用复方灵芝汤并随症加减治疗,0.5 a后用药同对照组。结果与结论：复方灵芝汤联合阿德福韦酯治疗慢性乙型病毒性肝炎可以提高疗效,且疗效稳定。     

阿德福韦酯和恩替卡韦治疗活动性肝硬化患者48周的临床疗效观察

目的观察阿德福韦酯和恩替卡韦治疗活动性肝硬化患者48周的疗效和不良反应。方法将60例活动性肝硬化患者，随机分为阿德福韦酯组30例，给予阿德福韦酯10mg／d；恩替卡韦组30例，给予恩替卡韦0．5mg／a，观察期均为48周。均给予常规护肝及支持、对症治疗。观察两组患者的肝肾功能、血清学标志物、HBVDNA、肝纤维化标志物及药物不良反应情况。结果两组患者肝功能各项指标的复常率、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。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。结论活动性肝硬化患者48周的抗病毒治疗，恩替卡韦的疗效与安全性均与阿德福韦酯相似，而病毒转阴率较阿德福韦酯高。     

New paradigms for the treatment of chronic hepatitis B

The main goals of chronic hepatitis B treatment should be the long-term suppression of viral replication to minimize disease progression and the risk for the development of hepatocellular carcinoma. Treatment end-points, depending on surrogate markers alone, in particular hepatitis B e-antigen seroconversion, may not be ideal for patients who acquire the disease early in life.
Currently-available drugs include interferons and oral nucleoside/nucleotide analogs. Although interferon therapy provides a finite treatment period, a significant proportion of patients may not respond, and long-term outcome is inconclusive. Long-term efficacy has been demonstrated for both lamivudine and adefovir. However, prolonged nucleoside/nucleotide analog therapy is associated with the emergence of drug-resistant mutations. Therefore, nucleoside/nucleotide analogs with a high genetic barrier and potent antiviral activity, such as entecavir, should be used to reduce the chance of developing drug-resistant mutations. Drugs with a low genetic barrier, including lamivudine and telbivudine, should be used in conjunction with early testing for antiviral response. This can predict favorable outcomes in the long term. The early detection of drug-resistant mutations should prompt clinicians to either add or switch to another agent with a different drug-resistance profile. There are currently no treatment models in the use of combination or sequential therapy in treatment-naïve patients.
To date, long-term treatment appears to be the most effective option. Despite recent advances made with better understanding on the natural history of chronic hepatitis B infection and with newer antiviral drugs available, challenges remain with respect to treatment criteria, treatment end-points, and duration of treatment.     

Failure of adefovir 20 mg to improve suboptimal response in lamivudine‐resistant hepatitis B patients treated with adefovir 10 mg and lamivudine

Summary. Nine patients with lamivudine‐resistant chronic hepatitis B infection who had been treated with adefovir 10 mg/day and had had a suboptimal response but did not have genotypic resistance to adefovir were treated with high‐dose adefovir (20 mg/day). The response to the increased dose of adefovir was compared with the response in 15 patients with a suboptimal response who did not receive an increase in the dose of adefovir. The increase in the dose of adefovir did not lead to a significant reduction in hepatitis B DNA when compared with patients maintained on the standard dose. These data suggest that increasing the dose of adefovir in patients with a suboptimal response does not lead to an improved response.     

两种阿德福韦酯治疗慢性乙型肝炎的成本-效果分析

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。     

Switching patients with lamivudine resistant chronic hepatitis B virus from tenofovir to adefovir results in less potent HBV-DNA suppression

The nucleotide analogues, tenofovir disoproxil fumarate and adefovir dipivoxil, inhibit viral replication and are both effective against the hepatitis B virus (HBV). In our department, tenofovir was prescribed in addition to lamivudine for the treatment of lamivudine resistant chronic hepatitis B. After registration of adefovir, 10 patients were switched to adefovir monotherapy. We studied changes in HBV-DNA and alanine aminotransferase (ALT) in these patients. The median treatment duration with tenofovir was 78 weeks resulting in a median viral load reduction of 5.4 (range 6.8-2.3) log(10) copies/mL compared to baseline (P = 0.005). Two patients had an increase >1 log(10) copies/mL during tenofovir treatment. After the switch to adefovir, six out of 10 patients had an HBV-DNA >4 log(10) copies/mL and the median HBV-DNA increased from 2.8 to 4.5 log(10) copies/mL (P = 0.017). The factors associated with relapse were HBV-DNA PCR positivity at the time of switch and genotype B or D. ALT levels at the beginning of tenofovir treatment also might be a factor. Retreatment with tenofovir (n = 3) resulted in a rapid decline in HBV-DNA. Tenofovir is a potent antiviral drug. Switching to adefovir resulted in viral relapse in 60% of patients and retreatment with tenofovir resulted again in viral decline, which suggests that tenofovir is a more potent antiviral agent.