Entecavir: a review of its use in the treatment of chronic hepatitis B in patien

StephenW

http://www.docguide.com/entecavir-review-its-use-treatment-chronic-hepatitis-b-patients-decompensated-liver-disease?hash=c8431e6c&eid=23652&alrhash=2f4244-e14fac0ff7ef1d5b0c78458126191858

Entecavir: a review of its use in the treatment of chronic hepatitis B in patients with decompensated liver disease; Keating GM; Drugs 71 (18), 2511-29 (Dec 2011)


The oral deoxyguanosine nucleoside analogue entecavir (Baraclude®) has potent activity against hepatitis B virus (HBV) and a high genetic barrier to resistance. This article reviews the clinical efficacy and tolerability of entecavir in the treatment of chronic hepatitis B in patients with decompensated liver disease, as well as summarizing its pharmacological properties. Entecavir 1 mg/day was more effective than adefovir dipivoxil 10 mg/day in the treatment of patients with chronic hepatitis B and decompensated liver disease, according to the results of a randomized, open-label, multicentre trial. Patients were either nucleos(t)ide naive or lamivudine experienced. The reduction from baseline in HBV DNA levels at week 24 (primary endpoint) was significantly greater with entecavir than with adefovir dipivoxil. The proportion of patients with HBV DNA levels of<300 copies/mL was also significantly greater with entecavir than with adefovir dipivoxil at weeks 24, 48 and 96, as was the proportion of patients with ALT normalization. Entecavir 0.5 or 1 mg/day, tenofovir disoproxil fumarate 300 mg/day and a fixed-dose combination of emtricitabine/tenofovir disoproxil fumarate 200 mg/300 mg per day were effective in the treatment of chronic hepatitis B in patients with decompensated liver disease, according to the 48-week analysis of a randomized, double-blind, multicentre trial, primarily designed to examine tolerability endpoints. In this trial, over one-third of patients had received previous therapy with lamivudine for ≥6 months. The efficacy of entecavir in treatment-naive patients with HBV-related decompensated cirrhosis did not significantly differ from that seen in patients with chronic hepatitis B or compensated cirrhosis (compensated group), according to the results of a prospective, nonrandomized study. After 6 or 12 months of entecavir treatment, there were no significant differences between the decompensated and compensated groups in virological, biochemical or serological endpoints. In patients with decompensated cirrhosis, significant improvements from baseline in liver function were seen after 12 months of entecavir therapy. Oral entecavir was generally well tolerated in patients with chronic hepatitis B and decompensated liver disease, with most of the reported treatment-emergent adverse events consistent with decompensated liver disease. In the trial primarily designed to examine tolerability endpoints, there was no significant difference between patients receiving entecavir and those receiving tenofovir disoproxil fumarate with or without emtricitabine in terms of the proportion of patients experiencing tolerability failure or the proportion of patients with confirmed increases in serum creatinine levels of ≥0.5 mg/dL above baseline or confirmed serum phosphorus levels of<2.0 mg/dL at week 48 (co-primary endpoints). It has been suggested that the risk of lactic acidosis associated with oral nucleos(t)ide analogue therapy is increased in patients with highly impaired liver function. However, only one case of lactic acidosis was reported among entecavir recipients across two clinical trials in patients with chronic hepatitis B and decompensated liver disease. Moreover, small studies found that the risk of lactic acidosis was not increased in patients with chronic hepatitis B and decompensated liver disease who received entecavir, compared with patients with non-HBV decompensated liver disease. In conclusion, entecavir is a valuable agent for the first-line treatment of chronic hepatitis B in patients with decompensated liver disease.

StephenW

恩替卡韦：审查了其在治疗慢性乙型肝炎失代偿性肝病患者使用;基廷通用药品71（18），2511-29（2011年12月）

口服脱氧鸟嘌呤核苷类似物恩替卡韦（博路定®）有较强的抗乙型肝炎病毒（HBV）的活动和高基因屏障的抵抗。本文评论的临床疗效和耐受恩替卡韦治疗慢性乙型肝炎患者失代偿性肝病，以及总结其药理特性。恩替卡韦1毫克/天，较阿德福韦​​酯10 mg /天治疗慢性乙型肝炎患者和失代偿性肝病的有效，根据一项随机，开放标签，多中心试验的结果。患者无论是核苷（酸）IDE天真或拉米夫定经历。在第24周（主要终点）HBV DNA水平从基线减少了显著更大恩替卡韦与阿德福韦相比。与HBV DNA水平<300拷贝/ ml的患者比例也显著高于恩替卡韦与阿德福韦酯24，48和96周，患者ALT正常化的比例。恩替卡韦0.5或1毫克/天，替诺福韦disoproxil富马酸300毫克/日和恩曲他滨/替诺福韦disoproxil富马酸200 mg/300毫克，每天固定剂量组合有效治疗慢性乙型肝炎失代偿性肝病患者，根据一项随机，双盲，多中心试验，主要目的是检查耐受性端点，48周的分析。在这项试验中，超过三分之一的患者收到拉米夫定≥6个月以前的治疗。恩替卡韦在治疗过的患者，HBV相关性肝硬化失代偿期的疗效不显着不同的慢性B型肝炎或代偿性肝硬化（补偿组）的患者中看到，根据一项前瞻性，非随机研究的结果。恩替卡韦治疗6个或12个月后，有病毒学，生化或血清学终点失代偿和补偿组之间没有显着性差异。失代偿期肝硬化患者，恩替卡韦治疗12个月后显著改善肝功能基线。口服恩替卡韦是慢性乙型肝炎和失代偿性肝病患者一般耐受性良好，与大多数报道的治疗失代偿性肝病的不良事件。试验主要目的是检查耐受性端点，接收或无恩曲他滨在经历证实血肌酐增加耐受失败的患者或患者的比例比例方面，恩替卡韦和那些接受替诺福韦disoproxil富马酸患者之间没有显著差异≥0.5毫克/升的水平高于基线或证实血磷水平<2.0毫克/升，48周（共同主要终点）。有人曾建议，与口腔nucleos相关的乳酸性酸中毒的风险（T）IDE模拟疗法是在高度肝功能受损的患者增加。但是，只有一个乳酸性酸中毒的情况下跨越两个临床试验报道在慢性乙型肝炎和失代偿性肝病患者，恩替卡韦收件人之间。此外，小规模研究发现，乳酸性酸中毒的危险并没有增加在慢性乙型肝炎和失代偿性肝病收到恩替卡韦的患者，较非乙肝失代偿性肝病患者。总之，恩替卡韦是一个慢性乙型肝炎的一线治疗失代偿性肝病患者的宝贵代理。