Hepatitis B Clinical Research Network Clinical Center: Michigan-Hawaii consortium

描述（由申请方提供）：急性B型肝炎病毒（HBV）感染发生率的降低尚未转化为慢性感染患病率的相应降低。目前，来自流行国家的移民约占美国所有慢性HBV感染新发病例的90%。美国人群种族/民族的多样性和许多HBV基因型的存在为研究宿主-病毒关系及其与临床结局的相关性提供了机会。目前，有6种获批的B型肝炎治疗方法，但这些治疗方法不能根除病毒。大多数患者需要长时间（或无限期）治疗以维持病毒抑制，导致抗病毒药物耐药性和负担能力的问题。关于B型肝炎治疗的关键问题是：何时开始，应使用哪种抗病毒药物，何时停止，以及对抗病毒药物耐药的患者怎么办？本临床中心申请包括2个研究中心：密歇根大学（安阿伯）和夏威夷医学中心东/夏威夷大学（檀香山）。Lok博士是B型肝炎的国际权威，在B型肝炎研究方面有着长期的成功记录，她将担任PI。蔡医生对B型肝炎有长期的临床和研究兴趣，并在社区外展计划方面有丰富的经验，他将担任该中心的主任。本临床中心申请的目的是进一步了解慢性B型肝炎病毒（HBV）感染的自然史、自发和治疗相关的病毒清除机制、抗病毒药物耐药HBV突变的流行病学和临床影响，并确定慢性B型肝炎患者的最佳治疗。为了实现这一目标，我们将与其他临床中心、数据协调中心、免疫学中心、病毒学中心和NIDDK项目办公室密切合作;并将遵守HBV临床研究网络（CRN）指导委员会的决定和所有HBV CRN委员会的政策。将建立一个数据库，以确定美国慢性HBV感染的谱、与疾病进展相关的因素以及临床实践中抗病毒药物耐药性的发生率。一项随机试验比较了恩替卡韦+替诺福韦与恩替卡韦与替诺福韦在核苷初治HBeAg+和HBeAg-的代偿性肝病患者中的重新组合，并将基因型耐药作为主要终点。其他重要主题的临床试验，如在免疫耐受期的患者的治疗和抗病毒耐药HBV患者的最佳管理也进行了讨论。

DESCRIPTION (provided by applicant): Decrease in incidence of acute hepatitis B virus (HBV) infection has not been translated into a corresponding decrease in prevalence of chronic infection. Currently, immigration from endemic countries accounts for roughly 90% of all new cases of chronic HBV infection in the US. The diversity of race/ethnicity of the US population and the presence of many HBV genotypes presents an opportunity to study host-virus relationships and their association with clinical outcomes. Currently, there are 6 approved treatments for hepatitis B, but these treatments do not eradicate the virus. Most patients require long (or indefinite) durations of treatment to maintain virus suppression, leading to problems with antiviral resistance and affordability. The key questions regarding hepatitis B treatment are: when to start, which antiviral agent(s) should be used, when to stop, and what to do in patients with antiviral resistance? This Clinical Center application comprises 2 sites: University of Michigan in Ann Arbor and Hawaii Medical Center East/University of Hawaii in Honolulu. Dr. Lok is an international authority on hepatitis B and has a long record of success in hepatitis B research, she will be the PI. Dr. Tsai has a long standing clinical and research interest in hepatitis B and has extensive experience in community outreach programs, he will be the co-l. The goals of this Clinical Center application are to further our understanding of the natural history of chronic hepatitis B virus (HBV) infection, the mechanisms of spontaneous and treatment related virus clearance, the epidemiological and clinical impact of antiviral drug-resistant HBV mutations, and to determine the optimal treatment for patients with chronic hepatitis B. To achieve this goal, we will work in close collaboration with the other Clinical Centers, the Data Coordinating Center, the Immunology Center, the Virology Center, and the NIDDK Project Office; and will comply with the decisions of the HBV Clinical Research Network (CRN) Steering Committee and the policies of all HBV CRN committees. A database will be established to determine the spectrum of chronic HBV infection in the US, factors associated with disease progression, and incidence of antiviral drug resistance in clinical practice. A randomized trial comparing de novo combination of entecavir + tenofovir vs. entecavir vs. tenofovir in nucleoside na¿ve HBeAg+ and HBeAg- patients with compensated liver disease with genotypic resistance as the primary endpoint is proposed. Clinical trials on other important topics such as treatment of patients in the immune tolerance phase and optimal management of patients with antiviral-resistant HBV are also discussed.