Durability of HBV DNA Suppression in Cirrhotics After Stopping Therapy

肝硬化患者停止治疗后 HBV DNA 抑制的持久性

• 批准号: 8545679
• 负责人: Harry Janssen
• 金额: $ 87.5万
• 依托单位: UNIVERSITY HEALTH NETWORK
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8545679
• 关键词: Adherence; Antiviral Agents; Antiviral Therapy; Chronic Hepatitis B; Cirrhosis; Clinical; Clinical Management; Clinical Treatment; Combined Modality Therapy; DNA; Data; Databases; Development; Double-Blind Method; Electronic Health Record; Epidemiology; Fibrosis; Guidelines; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B Virus; Immunologic Markers; Immunologics; Individual; Integration Host Factors; Interruption; Laboratories; Liver; Liver Failure; Liver Fibrosis; Malignant neoplasm of liver; Monitor; Oral; Outcome; Patients; Pharmaceutical Preparations; Placebo Control; Randomized; Resistance; Serious Adverse Event; Serological; Staging; Structure; Tenofovir; Testing; Therapeutic Intervention; Treatment Failure; Viral; Viral Load result; cost effectiveness; database structure; feeding; follow-up; health related quality of life; intrahepatic; mortality; safety testing; socioeconomics; treatment response; truvada

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.

描述（由适用提供）：已证明使用口服抗病毒剂对慢性肝炎（CHB）进行治疗可抑制病毒复制。有关于何时开始抗病毒疗法的准则，但何时开始启动治疗。这项研究取决于这样的论点，即努力使肝炎中肝炎的治疗耐用耐用的治疗反应（DOTR）是可取的，是可取的，这些肝炎感染了已完全且长期病毒抑制的晚期肝纤维化。初步数据表明，可以实现DOTR，并且如果对患者进行密切监测，即使在经过补偿的CIRRHotics中，也很少能在停止治疗后患有不良临床结果。这项研究是对结构化处理中断（STI）安全性的正式测试。我们的计划是在多中心，双盲，安慰剂控制的随机试验中评估Tenofovir（TDF）和Truvada，对治疗稳定，稳定的ciRRHOTICS，具有HBV DNA = 10 x 4副本/ml。具体目的是：1）测试2年后STI的安全性和成本效益，而连续病毒抑制的持续时间为4年（HBV DNA <70份/ml）； 2）测试4年是否优于连续和完全抑制的2年持续时间； 3）确定TDF和Truvada之间是否存在明显的差异； 4）为了确定定量的HBSAG水平，免疫标志物或ePATITIC CCCDNA水平是否可以预测达到DOTR的可能性。此外，我们提出了一种临床数据库结构，该结构可以促进临床管理，同时提供有关CHB流行病学以及基本的社会经济，文化和临床因素的信息，从而导致CHB结果。电子健康记录将将串行临床和实验室数据提供给数据库。临床提示将支持对治疗干预措施采取紧急行动的需求，并提供患者提醒以及时进行随访。该数据库将用于检查病毒和宿主因素如何影响晚期CHB患者中与生物有关的并发症的发展。这项研究的结果可能会为管理指南提供停止规则，这将构成该领域的重大进步。