The North Carolina Hepatitis Beta Clinical Research Network

描述(申请人提供)：慢性乙肝的最佳治疗方案仍存在争议。来自几个来源的已发表的指南建议，一般情况下，当血清ALT活性异常或存在重大肝病时，开始抗病毒治疗。这些建议在很大程度上是通过权衡在短期研究中衡量的应答可能性和在延长治疗期间产生病毒耐药性的可能性而制定的。然而，这些指南从未被前瞻性地评估，以确定它们是否真正代表了选择候选治疗的最佳策略。此外，最近的流行病学数据表明，高水平的乙肝病毒血症本身是随后的肝硬变和肝细胞癌的重要危险因素，这表明严格遵守治疗指南可能对许多患者不利，长期的病毒抑制对他们可能是有益的。目前可获得的多种高效抗病毒药物具有良好的安全性和看似较低的耐药风险，为优化治疗慢性乙肝的策略提供了机会。 这项建议将侧重于1)研究数据库和标本储存库的设计，以及2)多中心合作试验的设计，以证实当前的治疗指南，同时比较单一疗法和联合疗法的长期有效性和安全性。这项研究设计将进一步完善延长治疗期间乙肝病毒耐药性的识别和管理，并提供与治疗相关的长期结果的重要信息。我们提议作为这项合作研究的临床中心参与，将强调北卡罗来纳大学教堂山分校与杜克大学和卡罗莱纳医学中心合作的肝脏计划的经验、独特属性和患者群体，这将确保作为乙肝临床研究网络的成员成功完成这些研究。

DESCRIPTION (provided by applicant): The optimal treatment for chronic hepatitis B remains controversial. Published guidelines from several sources suggest initiating antiviral therapy, in general, when serum ALT activity is abnormal and when significant liver disease is present. These recommendations have largely been developed by balancing the likelihood of response as measured in short-term studies against the likelihood of developing viral resistance during extended therapy. However, these guidelines have never been prospectively evaluated to determine whether they truly represent the best strategy for selecting candidates for treatment. Furthermore, recent epidemiologic data indicate that the presence of high level HBV viremia itself is an important risk factor for subsequent cirrhosis and hepatocellular carcinoma, suggesting that rigid adherence to treatment guidelines may disadvantage many patients for whom long-term viral suppression may be beneficial. The current availability of multiple potent antiviral agents with good safety profiles and a seemingly low risk of resistance provide an opportunity to optimize strategies to treat chronic hepatitis B. This proposal will focus on the design of 1) a research database and specimen repository and 2) a collaborative multicenter trial to corroborate current treatment guidelines while comparing the long-term efficacy and safety of monotherapy vs. combination therapy. The study design will further refine the identification and management of hepatitis B viral resistance during extended therapy, and provide important information regarding the long-term outcomes associated with treatment. Our proposal to participate as a Clinical Center for this cooperative study will emphasize the experience, unique attributes, and patient population of the Liver Program at the University of North Carolina at Chapel Hill, in collaboration with Duke University, and Carolinas Medical Center, which will ensure successful completion of these studies as a member of the Hepatitis B Clinical Research network.