Hepatitis B Research Network Clinical Centers

 描述(由申请人提供)：北得克萨斯州乙肝联盟(NTHBC)由两家医疗机构和达拉斯沃斯堡大都会中心的三个不同的诊所组成。NTHBC全面参与了第一个为期7年的赠款周期，在13个参与网站中登记人数第三高，良好的保留率和持续参与免疫主动和免疫耐受临床治疗试验。Perrillo博士和Lee博士曾在各种委员会任职，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不同免疫学表现。沿着这些思路，NTHBC提出了一项关于目前探索不足的亚型的辅助研究，即同时存在乙肝表面抗原和抗-HBs。在这里，我们回顾了目前已知的关于这一异常患者组的情况，并试图将这一组患者与其他患者进行比较，比如由李博士监督的平行网络中的急性肝功能衰竭研究组。以往对乙肝相关性急性肝功能衰竭(HBVALF)的研究表明，超过50%的ALF患者同时存在HBs Ag和抗-HBs阳性。来自HBRN的数据表明，至少6%的慢性乙肝患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。一种解释可能是同时阳性是由于感染了不同的亚型，但这并没有得到证实，因为有数据表明所有的乙肝表面抗原基因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HBs Ag清除的时间以及疾病随时间的演变联系起来。更好地了解这一表型将为分子测序研究奠定基础，以便更好地了解同时阳性患者与HBVALF患者(通常更频繁的突变)和那些没有合并的慢性乙肝患者相比的突变情况。这些分析可能为导致慢性感染的乙肝病毒特异性免疫瘫痪提供新的重要见解，产生新的病毒清除策略。

 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.