The North Carolina Hepatitis Beta Clinical Research Network

北卡罗来纳州乙型肝炎临床研究网络

• 批准号: 8139899
• 负责人: MICHAEL W FRIED
• 金额: $ 22.02万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 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/8139899
• 关键词: Adherence; Antiviral Agents; Antiviral Response; Antiviral Therapy; Antiviral resistance; Appearance; Biological Assay; Chronic Hepatitis B; Cirrhosis; Clinical; Clinical Research; Clinical Trials; Collaborations; Combined Modality Therapy; Comorbidity; Data; Databases; Detection; Disadvantaged; Disease Progression; Eligibility Determination; Enrollment; Ensure; Equilibrium; Evolution; Future; Guidelines; Health Insurance Portability and Accountability Act; Hepatitis; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B Therapy; Hepatitis B Virus; Hepatitis B e Antigens; Immunology; Incidence; Individual; Institutional Review Boards; Liver; Liver diseases; Longitudinal Studies; Measures; Medical; Medical center; Methods; Minor; Multicenter Trials; Mutation; Natural History; North Carolina; Outcome; Participant; Pathogenesis; Patients; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Phenotype; Population; Primary carcinoma of the liver cells; Principal Investigator; Protocols documentation; Publishing; Race; Recommendation; Regimen; Registries; Relative (related person); Research; Research Design; Resistance; Resistance development; Risk; Risk Factors; Role; Safety; Sampling; Serological; Serum; Site; Source; Specimen; Tenofovir; Testing; Therapeutic; Tissues; Universities; Variant; Viral; Viremia; Virus; arm; cohort; cooperative study; data sharing; design; entecavir; epidemiologic data; experience; follow-up; insight; intrahepatic; meetings; member; novel; novel marker; patient population; prevent; programs; repository; response; therapy development; translational study; viral resistance; virology

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.

描述（由申请人提供）：慢性B型肝炎的最佳治疗仍存在争议。从几个来源发表的指南建议开始抗病毒治疗，一般来说，当血清ALT活性异常时，当存在显著的肝脏疾病时。这些建议在很大程度上是通过平衡短期研究中测量的应答可能性与扩展治疗期间发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，高水平的HBV病毒血症本身的存在是一个重要的危险因素，随后肝硬化和肝细胞癌，这表明严格遵守治疗指南可能会对许多患者不利，长期的病毒抑制可能是有益的。目前，多种有效的抗病毒药物具有良好的安全性和似乎较低的耐药风险，这为优化慢性B型肝炎的治疗策略提供了机会。 该提案将重点关注1）研究数据库和标本库的设计，以及2）协作多中心试验的设计，以证实当前的治疗指南，同时比较单药治疗与联合治疗的长期疗效和安全性。研究设计将进一步完善扩展治疗期间B型肝炎病毒耐药性的识别和管理，并提供与治疗相关的长期结局的重要信息。我们作为临床中心参与这项合作研究的提案将强调查佩尔山的北卡罗来纳州大学肝脏项目的经验、独特属性和患者人群，与杜克大学和科琳娜斯医学中心合作，这将确保作为B型肝炎临床研究网络的成员成功完成这些研究。