恩替卡韦治疗慢性乙型肝炎的研究现状

对恩替卡韦的药理学研究和临床试验结果进行了简要回顾。恩替卡韦可使未接受过核苷／酐类似物和拉米夫定抵抗的慢性乙型肝炎病人的肝脏组织学、血清病毒学和血清生化学得到改善。治疗剂量的思替卡韦有很少且轻微的不良反应。     

恩替卡韦序贯聚乙二醇化干扰素-α与单用恩替卡韦治疗慢性乙型肝炎的临床疗效比较:系统评价与分析

 目的 系统评价与分析恩替卡韦(ETV)序贯聚乙二醇化干扰素-α(Peg-IFN-α)与单用ETV在治疗慢性乙型肝炎患者中的临床疗效。方法 计算机检索PubMed、Embase、Cochrane Library、中国知网、万方数据库,搜索有关ETV及ETV序贯Peg-IFN-α治疗慢性乙型肝炎的随机对照试验研究,应用Stata 16.0软件对符合纳入条件的临床研究进行系统评价与分析。结果 共纳入10篇文献,1 250例患者,其中553例患者采用ETV序贯Peg-IFN-α治疗,697例患者单用ETV治疗,两组患者组间基线特征比较,差异均无统计学意义(均P＞0.05)。ETV序贯Peg-IFN-α试验组的HBsAg转换率、HBsAg清除率、HBeAg转换率、HBeAg清除率均高于ETV对照组,差异均有统计学意义(均P＜0.05)。结论 在慢性乙型肝炎抗病毒治疗中,总体上ETV序贯Peg-IFN-α治疗疗效优于单用ETV。     

恩替卡韦治疗乙型肝炎的疗效及安全性

恩替卡韦是一种有效的、选择性抑制乙型肝炎病毒复制的脱氧鸟嘌呤核苷类似物,由Bristol MyersSquibb公司研究开发,用于治疗乙型肝炎。体外试验表明,恩替卡韦比其他核苷类似物更有效。动物模型和人体临床研究结果显示,恩替卡韦具有极强的抑制乙型肝炎病毒复制,降低血清病毒DNA水平的作用,对耐拉米夫定的突变病毒株仍然有效,且未见明显的不良反应和线粒体毒性。     

Synthesis of [14C]‐radiolabelled entecavir

Radiolabelled [¹⁴C]entecavir, ( 1 ), was prepared in 12 steps from (1S,2R,3S,5R)‐3‐(benzyloxy)‐2‐(benzyloxymethyl)‐6‐oxa‐bicyclo[3.1.0]hexane 2 . The chemical yield of [¹⁴C]entecavir was 14% from the epoxide 2 . Introduction of [¹⁴C] radiolabel was achieved by elaboration of 4,5‐diaminopyrimidine 8 with triethyl[¹⁴C]orthoformate to purine derivative 9 . The radiochemical yield of [¹⁴C]entecavir from triethyl[¹⁴C]orthoformate was 11.3%. Radiochemical purity of [¹⁴C]entecavir determined by HPLC was 99.8%. The specific activity of [¹⁴C]entecavir was 108 µCi/mg (29.9 mCi/mmol). Copyright © 2005 John Wiley & Sons, Ltd.     

Nucleos(t)ide analogues for hepatitis B virus: Strategies for long-term success

Nucleoside and nucleotide analogues are potent HBV suppressors, but these agents rarely eradicate HBV. Therefore, the durability of viral response is a problem, and long-term therapy is usually required to ensure maintained HBV suppression. Studies have shown that long-term therapy starting with lamivudine may significantly improve survival, reduce the risk of liver-related major complications, and prevent the development of cirrhosis and HCC in chronic hepatitis B patients. However, drug resistance is a critical challenge during long-term nucleos(t)ide analogue maintenance therapy. The emergence of these mutants is characterized by an increasing level of serum HBV DNA, elevation of ALT level, and even hepatitis flare or decompensation. The prevention and proper management of drug resistance are crucial to ensure long-term success. To start treatment in the right patients at the right time with the right drug is essential in minimizing the problem of drug resistance. Each of these agents has a different profile of resistant mutations. In choosing a direct antiviral agent to initiate therapy, resistance profile is a crucial factor to consider, apart from potency and cost. In the case of drug resistance emerging, timely institution of a drug without cross-resistance may rescue the adverse effects of drug resistance and ensure the long-term success of nucleos(t)ide analogue therapy. To develop strategies for enhancing the therapeutic response and shortening the duration of therapy is an ultimate goal to avoid the problems of drug resistance.⁶⁸

• nucleos(t)ide analogues for hepatitis B virus (HBV) are highly effective in suppressing HBV replication but rarely eliminate the virus

• long-term therapy is usually required

• emergence of drug-resistant HBV mutations is a critical challenge

• to treat the right patient at the right time with the drug with highest genetic barrier to drug resistance is essential to minimize the problem with drug resistance

• the strategy of on-treatment adjustment based on level of suppression of HBV DNA needs to be clarified

• studies are needed to find the optimal combination therapy for both better therapeutic efficacy and less drug resistance

• oral antiviral agents able to attack cccDNA are urgently needed

乙肝肝硬化并发皮下脂膜炎样T细胞淋巴瘤伴噬血细胞综合征的治疗分析

目的 探讨乙肝肝硬化并发皮下脂膜炎样T细胞淋巴瘤(SPTCL)伴噬血细胞综合征(HPS)的临床特征和治疗方法。 方法 回顾性分析2014年8月第二军医大学附属东方肝胆外科医院1例乙肝肝硬化并发SPTCL伴HPS病例的临床资料。 结果 T细胞受体(TCR)表型不同则该病的侵袭性、治疗反应性及预后明显不同,伴HPS者治疗效果不佳,生存期短。 结论 乙肝肝硬化并发SPTCL伴HPS罕见,早期骨髓形态学、病理学、免疫组化及基因重排检测对确诊有重要意义,及早有效控制乙肝病毒尤为重要。早期诊断及治疗对延长患者生存期有重要意义。