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

描述(申请人提供)：乙肝病毒感染仍然是慢性肝病和肝癌的重要原因，影响着大约200万美国人和全球超过3.5亿人。尽管发现了疫苗，但慢性乙肝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，免疫系统在造成肝脏损伤和根除感染方面都发挥着重要作用，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。现在已经有了能够降低病毒负担的核苷类似物，从而改善了肝脏的炎症，但突变经常出现，药物在治疗不同阶段乙肝患者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没有意识到他们的疾病或在大多数情况下产生的治疗的明显好处。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%的慢性乙肝患者是亚裔，其中许多患者的疾病需要治疗，尽管ALT值在标准参考范围内--这一群体的治疗可能是有适应症的，但到目前为止还没有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。我们的建议回顾了目前对乙肝的了解，提供了关于达拉斯沃斯堡大都会医院乙肝负担的数据，以及调查人员为未来为拟议研究招募工作所具有的优势和经验。我们还提供了一个详细数据库的特定试验设计的概要，并回答了所提出的问题，即，具有高正常转氨酶水平的活跃的病毒型亚裔美国人在多大程度上受益于一种有效的、低抗性的核苷类似物的长期治疗。

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.