Hepatitis B Research Network Clinical Centers

乙型肝炎研究网络临床中心

• 批准号: 9321421
• 负责人: William M Lee
• 金额: $ 21.41万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 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 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9321421
• 关键词: Acute Hepatitis; Acute Liver Failure; Affect; American; Ancillary Study; Antibodies; Antigens; Attention; Carrier State; Categories; Characteristics; Chronic; Chronic Hepatitis B; Clinical; Cohort Studies; Common Epitope; Communication; Data; Disease; Enrollment; Ensure; Evolution; Fruit; Genotype; Goals; Grant; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis C; Hepatitis D; Immune; Immune System Diseases; Immune System and Related Disorders; Immune Tolerance; Immune system; Immunologics; Immunology; Incentives; Infection; Institution; Knowledge; Lead; Length; Life; Link; Liver Cirrhosis; Liver diseases; Location; Maintenance; Malignant neoplasm of liver; Medical; Molecular; Molecular Virology; Mutation; Patients; Phase; Phenotype; Plasma; Pregnancy; Recruitment Activity; Research; Research Design; Retrieval; Sampling; Serological; Serotyping; Site; Structure; System; Texas; Therapeutic; Therapy Clinical Trials; Therapy trial; Time; Translational Research; Ursidae Family; Viral; Virus; Virus Diseases; Virus Replication; Work; base; cohort; compliance behavior; exhaustion; experience; improved; insight; patient registry; protocol development; public health relevance; therapeutic development; treatment trial

 DESCRIPTION (provided by applicant): The North Texas Hepatitis B Consortium (NTHBC) comprises two medical institutions, and three distinct practice locations in the Dallas Fort Worth metroplex. NTHBC has participated fully in the first 7-year grant cycle, with the third highest enrollment among the 13 participating sites, good retention and ongoing participation in the Immune Active and Immune Tolerant clinical therapy trials. Drs. Perrillo and Lee have served on a variety of committees and proposed a number of ancillary studies, some of which are already under way. One of the goals of HBRN is to better define the varied immunologic presentations of chronic infection. Along these lines, the NTHBC proposes an ancillary study of a currently poorly explored sub-phenotype, that of concurrent hepatitis B surface antigen and anti-HBs. Herein, we review what is currently known about this anomalous group of patients, and seek to compare this group with others such as patients in a parallel network, the Acute Liver Failure Study Group, that is overseen by Dr. Lee. Prior studies in hepatitis B related acute liver failure (HBVALF) suggest that more than 50% of ALF patients are concurrently HBsAg and anti-HBs positive. Data from HBRN suggest that at least 6% of chronic hepatitis B subjects display this dual serologic status but appear to lack very active liver disease. One explanation might be that concurrent positivity results from infection with different subtypes but this is not substantiated y data suggesting common epitopes across all HBsAg genotypes and serotypes. The current study aims to explore the phenotype further, correlating it with clinical disease features, length of infection and time to subsequent HBsAg clearance and disease evolution over time. Understanding this phenotype better will lay the groundwork for molecular sequencing studies to better understand the mutation profile of the concurrently positive patients as compared to those with HBV ALF (typically more frequent mutations) and those with chronic hepatitis B without concurrence. These analyses are likely to offer new and important insights into HBV-specific immunological paralysis that leads to chronic infection, yielding new strategies for viral clearance.

 描述（由适用提供）：北德克萨斯丙型肝炎财团（NTHBC）包括两个医疗机构，以及达拉斯堡沃思堡Metroplex的三个不同的练习地点。 NTHBC已完全参与了第一个7年的赠款周期，在13个参与地点的入学人数中排名第三，良好的保留率以及持续参加免疫活性和免疫耐受耐受性临床治疗试验。博士。佩里洛（Perrillo）和李（Lee）曾在各种委员会任职，并提出了许多辅助研究，其中一些已经在进行中。 HBRN的目标之一是更好地定义慢性感染的不同免疫学表现。沿着这些线路，NTHBC提出了一项辅助研究，该研究对当前探索的亚表面型，即同时丙型肝炎表面抗原和抗HB的辅助研究。在本文中，我们回顾了目前对这一异常患者的了解，并试图将该组与诸如急性肝衰竭研究组中的患者（如李博士监督）进行比较。先前在丙型肝炎相关的急性肝衰竭（HBVALF）的研究表明，超过50％的ALF患者同时是HBSAG和抗HBS阳性。来自HBRN的数据表明，至少有6％的慢性乙型肝炎受试者表现出这种双重血清学状态，但似乎缺乏非常活跃的肝病。一种解释可能是，并发阳性是由不同亚型感染引起的，但不能证实y数据表明所有HBSAG基因型和血清型中的常见表位。当前的研究旨在进一步探索表型，将其与临床疾病特征，感染的长度以及随后的HBSAG清除率和随着时间的推移进化的时间相关。与HBV ALF（通常更频繁的突变）相比，更好地了解这种表型将为分子测序研究提供基础，以更好地了解同时阳性患者的突变特征，而患有慢性乙型肝炎的患者无关。这些分析可能会对导致长期感染的HBV特异性免疫瘫痪提供新的重要见解，从而产生新的病毒清除策略。