The North Carolina Hepatitis Beta Clinical Research Network

描述（由申请人提供）：慢性乙型肝炎的最佳治疗方法仍有争议。来自多个来源的已发表指南建议，一般来说，当血清ALT活性异常和存在显著肝脏疾病时，应开始抗病毒治疗。这些建议在很大程度上是通过平衡短期研究中测量的反应可能性与长期治疗期间产生病毒耐药性的可能性而制定的。然而，这些指南从未进行过前瞻性评估，以确定它们是否真正代表了选择治疗候选人的最佳策略。此外，最近的流行病学数据表明，高水平HBV病毒血症本身是随后肝硬化和肝细胞癌的一个重要危险因素，这表明严格遵守治疗指南可能会使许多长期病毒抑制可能有益的患者处于不利地位。目前可获得的多种有效抗病毒药物具有良好的安全性和看似低的耐药风险，为优化慢性乙型肝炎治疗策略提供了机会。

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.