North Texas Hepatitis B Consortium: Clinical Site for the Hepatitis B Network

描述（由申请人提供）：乙型肝炎病毒感染仍然是慢性肝病和肝癌的重要原因，影响约200万美国人和全球超过3.5亿人。尽管发现了疫苗，慢性的，通常是终身的乙型肝炎感染的负担在这个国家仍然很高，在国外更是如此。对其自然历史和发病机制的了解有所改善，但这种复杂感染的许多方面仍未得到我们的理解。例如，免疫系统在引起肝损伤和根除感染方面都起着重要作用，但迄今为止，增强免疫反应以改善病毒清除的努力都失败了。核苷类似物现在能够降低病毒负担，从而改善肝脏炎症，但突变经常发生，药物在不同阶段乙型肝炎患者管理中的作用仍然存在争议。此外，许多患有严重潜在肝病的患者不知道他们的疾病，也不知道在大多数情况下治疗的明显益处。需要在患者和医生教育方面做出新的努力，以接触到许多感染并可能从护理中受益的患者。在美国，大约50%的慢性乙型肝炎患者是亚裔，尽管ALT值在标准参考范围内，但其中许多患者的疾病值得治疗，这一群体可能需要治疗，但迄今为止尚未在任何对照试验中进行过试验。目前的区域区域协定就是为了应付这些挑战。我们的建议回顾了目前关于乙型肝炎的知识，提供了达拉斯沃斯堡大都会区乙型肝炎负担的数据，以及研究人员的优势和经验，为未来的研究招募工作做准备。我们还提供了一个详细数据库的特定试验设计大纲，并回答了所提出的问题，即，在多大程度上，具有高正常转氨酶水平的活跃病毒血症亚裔美国人从有效的低耐药性核苷类似物的长期治疗中获益。

DESCRIPTION (provided by applicant): Hepatitis B viral infection remains an important cause of chronic liver disease and liver cancer, affecting approximately 2 million Americans and more than 350 million people worldwide. Despite vaccine discovery, the burden of chronic, often lifelong hepatitis B infection remains high in this country and even more so abroad. Understanding its natural history and pathogenesis has improved but there are still many aspects of this complex infection that escape our understanding. For example, the immune system plays an important role both in causing liver damage and in its eradicating infection, but efforts thus far to heighten immune responses to improve viral clearance have failed. Nucleoside analogues are now available that are capable of lowering the viral burden, with resultant improvement in inflammation in the liver, but mutations arise frequently and the role of drugs in the management of patients with various phases of hepatitis B remains controversial. In addition, many patients with serious underlying liver disease are unaware of their disease or the clear benefits of treatment that accrue in most circumstances. New efforts at patient and physician education will be needed to reach the many patients who have infection and could benefit from care. Approximately 50% of patients with chronic hepatitis B in the US are of Asian ethnicity and many of these patients have disease that warrants treatment despite ALT values that fall within the standard reference range-treatment of this group is probably indicated but has not been tried in any controlled trial to date. The present RFA is intended to meet these challenges. Our proposal reviews current knowledge about hepatitis B, provides data on the burden of hepatitis B in the Dallas Fort Worth metroplex, and the strengths and experience of the investigators for future recruiting efforts for the proposed studies. We also provide the outline of a specific trial designs for a detailed database and to answer the concern raised, that is, to what extent do actively viremic Asian Americans with high normal aminotransferase levels benefit from a prolonged course of treatment with a potent, low resistance nucleoside analog.