Hepatitis B Research Network Clinical Centers

 描述（由申请人提供）：北德克萨斯B型肝炎联盟（NTHBC）由两个医疗机构和达拉斯沃斯堡大都市的三个不同的实践地点组成。NTHBC充分参与了第一个7年的资助周期，在13个参与站点中的第三高入学率，良好的保留率和持续参与免疫活性和免疫耐受临床治疗试验。Perrillo博士和Lee博士曾在多个委员会任职，并提出了一些辅助研究，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各种免疫学表现。沿着这些路线，NTHBC提出了一个辅助研究，目前探索不足的亚表型，即并发的B表面抗原和抗-HBs。在此，我们回顾了目前对这一异常患者群体的了解，并试图将这一群体与其他群体进行比较，例如由Lee博士监督的平行网络急性肝衰竭研究组中的患者。先前对B型肝炎相关急性肝衰竭（HBVALF）的研究表明，超过50%的ALF患者同时为HBsAg和抗-HBs阳性。来自HBRN的数据表明，至少有6%的慢性B型肝炎受试者表现出这种双重血清学状态，但似乎没有非常活跃的肝病。一种解释可能是同时阳性是由不同亚型的感染引起的，但这并没有得到证实，因为数据表明所有HBsAg基因型和血清型都有共同的表位。目前的研究旨在进一步探索表型，将其与临床疾病特征，感染时间和随后的HBsAg清除时间以及随时间的疾病演变相关联。更好地了解这种表型将为分子测序研究奠定基础，以更好地了解与HBV ALF（通常更频繁的突变）和慢性B型肝炎患者相比，同时阳性患者的突变谱。这些分析可能为HBV特异性免疫麻痹导致慢性感染提供新的重要见解，产生病毒清除的新策略。

 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.