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

描述（由申请人提供）：B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，但慢性、往往是终身的B型肝炎感染的负担在美国仍然很高，在国外更是如此。对它的自然史和发病机制的理解已经有所改善，但这种复杂的感染仍然有许多方面无法理解。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，提高免疫反应以改善病毒清除的努力都失败了。核苷类似物现在可用于降低病毒负荷，从而改善肝脏炎症，但突变频繁发生，药物在治疗不同阶段的B型肝炎患者中的作用仍存在争议。此外，许多患有严重基础肝病的患者不知道他们的疾病或在大多数情况下累积的治疗的明显益处。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，约50%的慢性B型肝炎患者为亚裔，尽管ALT值在标准参考范围内，但其中许多患者的疾病仍需要治疗-这组患者可能需要治疗，但迄今为止尚未在任何对照试验中进行过试验。目前的RFA旨在应对这些挑战。我们的提案回顾了目前对B型肝炎的认识，提供了达拉斯沃斯堡大都市B型肝炎负担的数据，以及研究者的优势和经验，以便将来为拟议的研究招募人员。我们还提供了一个详细的数据库，并回答提出的问题，即在何种程度上积极病毒血症的亚裔美国人与正常转氨酶水平高受益于一个强大的，低耐药核苷类似物的长期治疗过程中的具体试验设计的大纲。

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.