两种不同品牌恩替卡韦治疗慢性乙型肝炎成本分析

慢性乙型肝炎(CHB)是慢性疾病,抗病毒治疗用药时间较长,患者所需费用较高,选择安全、有效、经济的药物治疗,对减轻患者经济负担,增加患者用药的依从性具有一定的现实意义.恩替卡韦是鸟嘌呤核苷类似物,在体内经磷酸化后转化为具有活性的三磷酸盐形式,抑制病毒多聚酶的活性,从而抑制乙型肝炎病毒(HBV)复制.文中通过对两种不同品牌恩替卡韦治疗CHB的成本进行分析,为患者选择药品提供参考.     

恩替卡韦治疗乙型肝炎肝硬化临床疗效观察

<正>恩替卡韦是一种口服的脱氧鸟嘌呤核苷类似物,对活动性乙型肝炎病毒(HBV)具有强有力抑制作用和高基因屏障的抵抗作用。我院消化科选取了乙型肝炎肝硬化患者29例,应用恩替卡韦治疗48周,以观察其疗效,现总结如下。1资料与方法     

某院2009～2011年抗HBV核苷类似物的应用分析

目的分析我院抗乙型肝炎病毒(HBV)核苷类似物的使用情况,为临床合理用药提供参考。方法利用我院计算机管理软件检索2009至2011年口服抗HBV核苷类似物的销售数量、销售金额、用药频度(DDDS)、日均费用(DDDc)进行统计分析。结果抗HBV核苷类似物的销售金额呈快速增长之势;用药频度排序前三位的品种为阿德福韦酯、拉米夫定及恩替卡韦;恩替卡韦的用药频度增幅最大。结论核苷类似物已成为治疗慢性乙型肝炎(CHB)的首选药物,市场前景看好。     

3种核苷类似物治疗慢性乙型肝炎的耐药性和安全牲探讨

目的探讨3种核苷类似物在治疗慢性乙型肝炎时所表现的耐药性和不良反应。方法查阅国内外参考文献,结合临床所见,并归纳总结。结果 3种核苷类似物在治疗慢性乙型肝炎时,临床中都出现了一定程度的耐药,但阿德福韦和恩替卡韦较拉米夫定在安全性和耐药性方面有明显的优势,特别是对于拉米夫定耐药的乙型肝炎病毒株有显著的抑制作用。结论 3种核苷类似物在治疗慢性乙型肝炎时,在抑制病毒复制的同时,会产生不同程度的耐药,临床中如何选择治疗方案,如何最大限度的减少或避免病毒耐药,是非常值得重视的临床问题。     

恩替卡韦——慢性乙肝治疗的候选药物

据WHO报道，全球超过20亿人已感染乙型肝炎病毒(HBV)，其中约4亿人患有慢性乙型肝炎，这种感染与肝硬化和肝癌病死率的风险增加关联。口服核苷类似物恩替卡韦是HBV聚合酶选择性抑制剂，具有较强的抗HBV作用。美国肝病协会的55届会议上报道了3项随机、双盲、Ⅲ期、多中心临床试验，比较了恩替卡韦和拉米夫定(标准疗法)对慢性乙肝患者的肝组织和病毒抑制的疗效。     

恩替卡韦抗乙型肝炎病毒及治疗慢性乙型肝炎的研究概况

恩替卡韦（Entecavir,ETV）于2005年上市并应用于临床,是美国食品与药品管理局（FDA）继批准拉米夫定（Lamivudine,LVD）和阿德福韦（Adefovir,ADV）后第3个用于治疗乙型肝炎病毒（HBV）的鸟嘌呤核苷类似物,它是乙型肝炎病毒脱氧核糖核酸（HBVDNA）多聚酶强抑制剂,能同时抑制病毒DNA复制的启动和延伸阶段,具有很强的抗病毒作用,且安全性好,耐药发生率低,是目前临床治疗慢性乙型肝炎（CHB）的代表药物,临床应用研究日趋深入。现就近年来ETV抗HBV及治疗CHB的研究作一综述。     

慢性乙型肝炎的抗病毒治疗进展

核苷类药物拉米夫定在抑制乙型肝炎病毒(HBV)复制、降低病毒载量、降低血清丙氨酸转移酶、改善e抗原及肝组织炎性坏死等方面取得了确切的疗效。但长期应用拉米夫定可导致HBV发生变异，降低病毒对拉米夫定的敏感性，停药后可出现病毒复制和反跳。此外，核苷类药物阿德福韦酯和恩替卡韦对乙肝亦有一定的疗效。该文对上述药物治疗乙肝的进展进行了综述。     

乙型肝炎病毒的耐药和耐药管理

抗病毒治疗是慢性乙型肝炎(以下简称乙肝)最根本的治疗方法,目前公认有效的抗乙型肝炎病毒(HBV)药物主要包括干扰素(IFN)类和核苷(酸)类似物.自1998年拉米夫定在全球上市以来,迄今已有拉米夫定(LAM)、阿德福韦酯(ADV)、恩替卡韦(ETV)和替比夫定(LdT)共4种核苷(酸)类似物获国家食品药品监督管理局(SFDA)批准用于抗HBV治疗.相对于干扰素,口服核苷(酸)类似物治疗具有方便有效的优点,但该类药物只有长期治疗才有望实现持久应答,使得HBV产生耐药性的风险大大增加.     

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。     

核苷类抗病毒药的耐药性

我国是世界上乙型肝炎病毒(HBV)携带最多的国家,庞大的乙型肝炎基础人群造成发生终末期肝病以及死于HBV相关疾病的数量居高不下,严重影响了患者的生活质量和寿命[1]。近几年,随着核苷类抗病毒药研究的不断深入,新药的研发进展迅速。拉米夫定(LAM)、阿德福韦酯(ADV)、恩替卡韦、替比夫定等一系列核苷类似物相继上市,为病毒性肝炎的治疗提供了强大的武器。核苷类似物以其抗病毒疗效确切、不     

Entecavir: a potent new antiviral drug for hepatitis B

Entecavir, a new deoxyguanine nucleoside analogue, is a selective inhibitor of the replication of the hepatitis B virus. In vitro this compound has proven to be far more effective than other nucleoside analogues. In animal models, an impressive reduction of serum viral DNA has been observed with covalently closed circular DNA and hepatitis B viral core antigen negativity in liver biopsy specimens. In clinical studies, entecavir revealed excellent suppression of hepatitis B virus replication without significant side effects or evidence of mitochondrial toxicity. Until now, no entecavir-resistant viral mutants have been described. Prolonged therapy as well as prophylactic therapy, for example, in liver transplant recipients, is feasible and not limited by breakthrough infections. Data on entecavir therapy for treatment of nucleoside-naive, wild-type hepatitis B virus is being generated in Phase III clinical trials worldwide for both hepatitis B envelope antigen-positive and -negative subpopulations, as well as in lamivudine-resistant patients. Based on mechanism and potency of interferon and entecavir, clinical trials with combination therapy are eagerly awaited.     

Entecavir: a potent new antiviral drug for hepatitis B

Entecavir, a new deoxyguanine nucleoside analogue, is a selective inhibitor of the replication of the hepatitis B virus. In vitro this compound has proven to be far more effective than other nucleoside analogues. In animal models, an impressive reduction of serum viral DNA has been observed with covalently closed circular DNA and hepatitis B viral core antigen negativity in liver biopsy specimens. In clinical studies, entecavir revealed excellent suppression of hepatitis B virus replication without significant side effects or evidence of mitochondrial toxicity. Until now, no entecavir-resistant viral mutants have been described. Prolonged therapy as well as prophylactic therapy, for example, in liver transplant recipients, is feasible and not limited by breakthrough infections. Data on entecavir therapy for treatment of nucleoside-naive, wild-type hepatitis B virus is being generated in Phase III clinical trials worldwide for both hepatitis B envelope antigen-positive and -negative subpopulations, as well as in lamivudine-resistant patients. Based on mechanism and potency of interferon and entecavir, clinical trials with combination therapy are eagerly awaited.     

New therapeutic strategies in the treatment of hepatitis B virus infection

Principally, because of the association of the chronic carrier state with the development of cirrhotic liver disease and hepatocellular carcinoma, chronic hepatitis B infection is a public health problem of global significance. In the main, therapy for chronic hepatitis B is limited to the use of alpha interferon for a limited number of chronic hepatitis B virus (HBV) carriers who have chronic hepatitis with active viral replication. The development of antiviral nucleoside analogues for the herpes viruses and human immunodeficiency virus (HIV) has resulted in the identification of several compounds which also have activity against HBV. Unfortunately, these agents have not been associated with the clearance of hepatitis B infection, but rather only the suppression of active infection while the patient is receiving medication. In addition, the development of drug-resistance to these agents by the virus will most likely limit their long-term efficacy. Gene therapy has recently been applied to HBV both in vitro and in vivo. This has included the use of antisense oligodeoxynucleotides and RNA, ribozymes, dominant negative mutants and therapeutic HBV vaccines. These newer therapeutic modalities may hold promise as effective treatments for chronic hepatitis B, but to date, have been limited by the problem of delivery to the target cell population or infected organ in vivo. Combination nucleoside analogue therapy may also provide an important treatment modality for chronic hepatitis B, although this will require further investigation.     

Review article: hepatitis B and liver transplantation

Liver transplantation is an excellent treatment for hepatitis B virus infected patients who have acute or chronic liver failure and/or primary liver cancer. Advances in antiviral prophylaxis prevent clinically significant graft re-infection for the majority of patients. Graft and patient survival has improved significantly during the past decade, and results of transplantation for hepatitis B virus are now superior to those achieved for most other indications. In particular, the availability of lamivudine and adefovir have transformed outcome. The addition of lamivudine to passive immunoprophylaxis with hepatitis B virus immunoglobulin prevents re-infection in most cases. Adefovir should be added to this combination when the patient develops lamivudine resistance before transplantation. The significance of serum hepatitis B virus DNA positivity in the absence of circulating hepatitis B surface antigen is uncertain. Hepatitis B virus infection of the graft can be observed when prophylaxis is inadequate, when the donor liver contains latent hepatitis B virus infection (so-called de novo infection from the hepatitis B virus core antibody positive donor), and when the donor is exposed to third party infection (sexual or nosocomial transmission). Established hepatitis B virus graft infection is a good indication for combination nucleoside analogue therapy. Combination therapy can achieve sustained suppression of viral replication, and hepatitis B e antigen and hepatitis B surface antigen clearance can also be observed.     

Clevudine for the treatment of chronic hepatitis B virus infection

Chronic hepatitis B virus (HBV) infection is a major health problem that is responsible for < or = 1 million deaths and 500,000 cases of hepatocellular carcinoma worldwide each year. Drugs that are currently approved by the FDA for the treatment of chronic HBV consist of two groups: the immunomodulators, such as conventional IFN-alpha and pegylated IFN-alpha2a; and nucleoside/nucleotide analogues, such as lamivudine, adefovir dipivoxil and entecavir. However, due to the limitations of these agents, newer agents with improved efficacy are currently being developed. One nucleoside/nucleotide analogue that is drawing a wide range of interest is clevudine, which is an analogue of the unnatural beta-L configuration. In the woodchuck hepatitis virus (WHV), clevudine 10 mg/kg has proven to be effective in suppressing viral replication with < or = 9 log10 decreases in WHV. At this dose, a significant reduction of intrahepatic WHV RNA and covalently closed circular WHV DNA levels can also be observed. Treatment with clevudine 10 mg/kg can confer additional antiviral benefit in the form of a more sustained reduction in WHV replication, serum woodchuck hepatitis surface antigen and intrahepatic woodchuck hepatitis core antigen expression following the withdrawal of clevudine. In humans, clevudine 10, 50, 100 or 200 mg/day for 28 days can reduce the median HBV DNA by -2.5, -2.7, -3 and -2.6 log10, respectively. More importantly, this suppression of antiviral activity is maintained at 12 and 24 weeks post treatment. Based on the early results of clevudine, more large-scale human studies with clevudine monotherapy or combination therapy is eagerly awaited.     

LB80380: a promising new drug for the treatment of chronic hepatitis B

Hepatitis B virus is a significant cause of liver cirrhosis and hepatocellular carcinoma in patients with chronic infection. Higher levels of viral load are associated with increased risk of developing liver-related complications. The current available oral therapies suppress viral replication through their action on the hepatitis B virus polymerase. As treatment with oral nucleoside/nucleotide analogues is associated with the development of drug-resistant mutations, there is continuing research for newer and more potent antiviral agents to reduce the chance of drug resistance. LB80380, a prodrug, is an oral nucleotide analogue that inhibits viral replication by incorporation into the viral DNA. Antiviral activity against wild-type virus and virus with drug-resistant mutations was demonstrated in Phase II trials, with significant reduction of viral load in patients treated with LB80380. LB80380 was also shown to be safe and well tolerated.     

LB80380: a promising new drug for the treatment of chronic hepatitis B

Hepatitis B virus is a significant cause of liver cirrhosis and hepatocellular carcinoma in patients with chronic infection. Higher levels of viral load are associated with increased risk of developing liver-related complications. The current available oral therapies suppress viral replication through their action on the hepatitis B virus polymerase. As treatment with oral nucleoside/nucleotide analogues is associated with the development of drug-resistant mutations, there is continuing research for newer and more potent antiviral agents to reduce the chance of drug resistance. LB80380, a prodrug, is an oral nucleotide analogue that inhibits viral replication by incorporation into the viral DNA. Antiviral activity against wild-type virus and virus with drug-resistant mutations was demonstrated in Phase II trials, with significant reduction of viral load in patients treated with LB80380. LB80380 was also shown to be safe and well tolerated.     

Rolling review–the pathogenesis, diagnosis and management of viral hepatitis

Five major hepatotrophic viruses have been identified. The pathogenesis, diagnosis and treatment of chronic viral hepatitis continues to be intensely researched. Experimental evidence suggests that HLA restricted virus-specific T cells play a role in hepatocellular injury in type A hepatitis. The absence of chronic infection indicates the effectiveness of the host immune response to hepatitis A virus (HAV). It is postulated that HAV may rarely trigger an autoimmune chronic hepatitis. Active prophylaxis of hepatitis A is possible. The elimination of hepatitis B is dependent on the recognition of viral determinants in association with HLA proteins on infected hepatocytes by cytotoxic T cells. The specific epitopes recognized by B and T cells are being mapped. Polymerase chain reaction (PCR) amplification and sequencing of genomic DNA in patients with chronic hepatitis B has indicated that nucleotide substitutions in the genome are not uncommon. Their pathogenicity is being explored. Antiviral therapy for hepatitis B remains difficult. Interferon is effective in a proportion of patients. Thymosin may prove to be more effective immunomodulatory therapy. New nucleoside analogues suppress HBV replication, but the safety of these drugs has been questioned after the appearance of severe liver toxicity with fialuridine. The data that hepatitis D virus is pathogenic has recently been challenged with the observation that HDV re-occurs in transplanted liver after engrafting, but without signs of HBV recurrence or evidence of liver damage. Treatment of hepatitis D virus remains difficult. Several isolates of hepatitis C virus have been cloned, and the sequence divergence of these isolates indicates that there are several major genotypes and component subtypes of this polymorphic virus. Hypervariability of regions of the HCV envelope proteins may be important in persistence of HCV infection and immunopathogenesis. Type C hepatitis has a complex natural history, and several systemic manifestations as well as autoimmune disease have been linked to hepatitis C infection. Alpha interferon is beneficial in 25–30% of patients; certain genotypes may be more sensitive to interferon therapy. The hepatitis E virus causes acute, and in susceptible populations, fulminant hepatitis. The diagnosis can now be made with tests for anti-HEV and Polymerase chain reaction. Other forms of viral hepatitis, particularly those associated with fulminant hepatitis, severe sporadic hepatitis and autoimmune disease are being sought.     

Clevudine for the treatment of chronic hepatitis B virus infection

Chronic hepatitis B virus (HBV) infection is a major health problem that is responsible for ≤ 1 million deaths and 500,000 cases of hepatocellular carcinoma worldwide each year. Drugs that are currently approved by the FDA for the treatment of chronic HBV consist of two groups: the immunomodulators, such as conventional IFN-α and pegylated IFN-α2a; and nucleoside/nucleotide analogues, such as lamivudine, adefovir dipivoxil and entecavir. However, due to the limitations of these agents, newer agents with improved efficacy are currently being developed. One nucleoside/nucleotide analogue that is drawing a wide range of interest is clevudine, which is an analogue of the unnatural β-L configuration. In the woodchuck hepatitis virus (WHV), clevudine 10 mg/kg has proven to be effective in suppressing viral replication with ≤ 9 log₁₀ decreases in WHV. At this dose, a significant reduction of intrahepatic WHV RNA and covalently closed circular WHV DNA levels can also be observed. Treatment with clevudine 10 mg/kg can confer additional antiviral benefit in the form of a more sustained reduction in WHV replication, serum woodchuck hepatitis surface antigen and intrahepatic woodchuck hepatitis core antigen expression following the withdrawal of clevudine. In humans, clevudine 10, 50, 100 or 200 mg/day for 28 days can reduce the median HBV DNA by -2.5, -2.7, -3 and -2.6 log₁₀, respectively. More importantly, this suppression of antiviral activity is maintained at 12 and 24 weeks post treatment. Based on the early results of clevudine, more large-scale human studies with clevudine monotherapy or combination therapy is eagerly awaited.     

拉米夫定治疗乙型肝炎的抗病毒疗效和耐药性

拉米夫定是第1个正式进入临床治疗慢性乙型肝炎病毒(HBV)感染的口服核苷类药物。现对拉米夫定治疗乙型肝炎病毒感染的作用特点、临床应用、病毒变异以及对疗效的影响进行综述。