Durability of HBV DNA Suppression in Cirrhotics After Stopping Therapy

描述（由申请方提供）：使用口服抗病毒药物治疗慢性B型肝炎（CH B）已显示可抑制病毒复制。有关于何时开始抗病毒治疗的指南，但没有关于何时停止治疗的指南。本研究的论点是，这是安全和可取的，奋进达到持久的停药反应（DOTR）治疗的B型肝炎感染的个人与晚期肝纤维化谁已经完全和长期的病毒抑制。初步数据表明，DOTR是可以实现的，即使在代偿性心律失常患者中，如果对患者进行密切监测，停止治疗后也很少出现不良临床结局。本研究是对结构性治疗中断（STI）安全性的正式测试。我们的计划是在一项多中心、双盲、安慰剂对照的随机试验中评估替诺福韦（TDF）和特鲁瓦达对HBV DNA =10 × 4拷贝/mL的初治稳定、代偿良好的抗病毒药物的疗效。具体目标是：1）测试连续和完全病毒抑制2年与4年后STI的安全性和成本效益（2）检测持续完全抑制4年是否优于持续完全抑制2年的上级时间;和4）确定定量HBsAg水平、免疫标志物或肝内cccDNA水平是否可以预测实现DOTR的可能性。此外，我们提出了一个临床数据库结构，它可以促进临床管理，同时提供有关CHB流行病学和潜在的社会经济，文化和临床因素，有助于CHB的结果的信息。电子健康记录将把连续的临床和实验室数据输入数据库。临床提示将有助于采取治疗干预措施的紧急行动，并提醒患者及时采取后续行动。该数据库将用于研究病毒和宿主因素如何影响晚期CHB患者肝脏相关并发症的发展。这项研究的结果可能会产生管理指南的停止规则，这将是该领域的一个重大进步。

DESCRIPTION (provided by applicant): Therapy of chronic hepatitis B (CHB) using oral antiviral agents has been shown to suppress viral replication. There are guidelines on when to start antiviral therapy but none on when to stop therapy once initiated. This study hinges on the argument that it is safe and desirable to endeavor to attain a durable off-treatment response (DOTR) to therapy in hepatitis B infected individuals with advanced liver fibrosis who have had complete and long-term viral suppression. Preliminary data demonstrate that a DOTR can be achieved and that it is rare to have adverse clinical outcomes after stopping therapy even in compensated cirrhotics if patients are closely monitored. This study is a formal test of the safety of structured treatment interruption (STI). Our plan is to evaluate Tenofovir (TDF) and Truvada in a multi-centre, double-blinded, placebo-controlled randomized trial of treatment-na¿ve stable, well-compensated cirrhotics with HBV DNA =10 X 4 copies/mL. Specific aims are: 1) to test the safety and cost-effectiveness of an STI after 2 years vs 4 years duration of continuous and complete viral suppression (HBV DNA <70 copies/mL); 2) to test whether 4 years is superior to 2 years duration of continuous and complete suppression; 3) to identify if there are marked differences between TDF and Truvada; and 4) to determine if quantitative HBsAg levels, immune markers, or intrahepatic cccDNA levels can predict the likelihood of achieving a DOTR. In addition, we propose a clinical database structure which can facilitate clinical management while providing information on the epidemiology of CHB and the underlying socioeconomic, cultural, and clinical factors that contribute to outcomes in CHB. Electronic health records will feed serial clinical and laboratory data into the database. Clinical prompts will facilitate the need for urgent action with therapeutic interventions and deliver patient reminders for timely follow-up. The database will be used to examine how viral and host factors influence the development of liver-related complications in patients with advanced CHB. Results from this study could produce stopping rules for management guidelines, which would constitute a major advancement in the field.