STUDIES OF THE NATURAL HISTORY AND TREATMENT OF CHRONIC HEPATITIS B

感染B型肝炎病毒是世界范围内肝病的主要原因，在美国占慢性肝病和肝硬化的5- 10%。目前已有安全有效的疫苗预防B型肝炎。然而，一旦疾病发生，其治疗是不令人满意的。α干扰素是第一个被证明对这种疾病有效的抗病毒药，并于1993年在美国获得许可用于这种适应症。获得许可的部分依据是NIH肝病科进行的研究。然而，α干扰素只对三分之一的典型慢性B型肝炎患者有效，它在这种疾病的非典型形式中的作用仍不清楚。肝病科目前的活动集中在开发更好的治疗方法以预防长期后果。拉米夫定治疗典型和非典型慢性B型肝炎的初步研究正在进行中。丁型肝炎患者对拉米夫定均无反应。与此相反，几乎所有慢性B型肝炎患者在服用拉米夫定100 mg每日一次后均出现血清生化、病毒学和组织学应答。然而，超过50%的患者出现了病毒耐药性的突破。拉米夫定的长期安全性和益处正在评估中。病毒耐药的患者将单独使用新的抗病毒药物（阿德福韦）或与拉米夫定联合使用。对抗病毒治疗有长期反应的患者将评估病毒是否仅被抑制并且仍然以低水平存在或被根除并且即使在肝脏中也不再可检测到。将在长期应答者和无应答者之间比较对肝炎抗原的免疫应答，以试图剖析从B型肝炎恢复的免疫学和病毒学决定因素。- 抗病毒/干扰素/核苷类似物/联合治疗-人类受试者

Infection with hepatitis B virus is a major cause of liver disease worldwide and accounts for 5-10 per cent of chronic liver disease and cirrhosis in the United States. Safe and effective vaccines are now available for prevention of hepatitis B. However, therapies for the disease once it has occurred are unsatisfactory. Alpha interferon was the first antiviral agent shown to be effective in this disease and was licensed for this indication in the United States in 1993. The basis for licensure were, in part, studies conducted in the Liver Diseases Section of NIH. However, alpha interferon is effective in only one- third of patients with typical chronic hepatitis B and its role in atypical forms of this disease remain unclear. Current activities in the Liver Diseases Section are focused on developing better therapies to prevent long-term consequences. A pilot study of lamivudine for typical and atypical forms of chronic hepatitis B is being conducted. Patients with delta hepatitis have uniformly failed to respond to lamivudine. In contrast virtually all patients with chronic hepatitis B have had a serum biochemical, virological and histological response to lamivudine in a dose of 100 mg once daily. However, breakthrough with viral resistance has occurred in more than 50 percent of patients. Long-term safety and benefit of lamivudine are now being evaluated. Patients with viral resistance will be evaluated using new antivirals (adefovir) alone or in combination with lamivudine. Patients who have had a long term response to antiviral therapy will be evaluated for whether the virus is merely suppressed and is still present in low level or is eradication and no longer detectable even in liver. Immune responses to hepatitis antigens will be compared between long term responders and non responders to attempt to dissect out the immunology and virologic determinants of recovery from hepatitis B. - Antiviral/Interferon/Nucleoside Analog/Combination Therapy - Human Subjects