DELTA HEPATITIS AND LIVER DISEASE IN HEMOPHILIACS

慢性肝病被怀疑是负责5-11%的 血友病患者的死亡案例 B型肝炎病毒的频率 (HBV)这一人群中的标记物没有明显变化， 1975年，对献血者血液进行HBsAg筛查成为强制性的。 虽然许多 血友病患者被认为患有非甲非乙型肝炎（NANB）， 虽然他们的肝脏疾病的原因，活动性感染HBV仍然占 合理比例的案件。 最近，一种新的 丁型肝炎病毒（HDV），增强了我们对 慢性肝病的免疫发病机制。 独特的 HDV的特征是它依赖于HBV的复制， 表情 B型肝炎患者重叠感染HDV通常导致 严重并最终致命的疾病。 正因为如此， 担心HDV可能导致更严重的 在患有B型肝炎的血友病患者中发现的一种慢性肝病。 从凝血因子中去除或去除该病毒的方法 浓缩物，例如通过热灭活，显然还没有被 成功 本提案的长期目标和具体目标 是为了确定HDV在大群血友病患者中的患病率， 并阐明HDV在HDV发生和发展中的作用， 这一人群中的肝脏疾病。 将建立活动性HDV感染 通过采用敏感的、非侵入性的血清学技术， 已开发了HDV RNA/cDNA探针，用于检测HDV RNA， 免疫印迹法检测HDAg。 这些测试应该可以避免 做肝活检来确认丁型肝炎病毒感染 纵向研究， 监测肝功能，评估淋巴细胞标志物的变化， 评估迟发型超敏反应将有助于确定 HBV和HDV联合感染在临床上是否比 与NANB肝炎或HBV单独相关的感染。 的存在和 血清和外周血单个核细胞中HBV DNA的物理状态 血友病患者外周血单个核细胞（PBMC）的表达与血清HDV的检测有关。 同样，本研究将确定是否存在PBMC相关的 一些“HBV免疫”患者体内的HBV DNA足以允许复制 关于HDV 最后，血友病患者的家庭成员将被检查， HBV、HDV和NANB肝炎感染的证据，以确定 这些病原体在家庭环境中传播的风险。

Chronic liver disease is suspected to be responsible for 5-11% of the deaths that occur among hemophiliacs. The frequency of hepatitis B virus (HBV) markers in this population has not changed appreciably since screening of donor blood for HBsAg became mandatory in 1975. While many hemophiliacs are believed to have non-A, non-B (NANB) hepatitis as the cause of their liver disease, active infection with HBV still accounts for a reasonable proportion of the cases. Recently, the discovery of a new viral agent, hepatitis delta virus (HDV), has enhanced our understanding of the immunopathogenesis of chronic liver disease. The unique characteristics of HDV is that it is dependent on HBV replication for its expression. Superinfection of hepatitis B patients with HDV often leads to severe and ultimately fatal disease. Because of this, there is a growing concern that HDV may be responsible for the development of more serious form of chronic liver disease seen in hemophiliacs with hepatitis B. Methods to remove or inactivate this virus from clotting factor concentrates, e.g. by heat-inactivation, apparently have not been successful. The long-term objectives and specific aims of this proposal are to determine the prevalence of HDV in a large cohort of hemophiliacs and to elucidate the role of HDV in the development and progression of liver disease in this population. Active HDV infection will be established by employing sensitive, noninvasive serologic techniques that have recently been developed, such as HDV RNA/cDNA probes to detect HDV RNA and an immunoblotting method to detect HDAg. These tests should avert the need for a liver biopsy to verify HDV infection. Longitudinal studies to monitor liver function, assess alterations in lymphocyte markers, and evaluate delayed type hypersensitivity reactions will help determine whether combined HBV and HDV infections are clinically more serious than infections associated with NANB hepatitis or HBV alone. The presence and physical state of HBV DNA in serum and peripheral blood mononuclear cells (PBMC) of hemophiliacs will be related to the detection of HDV in serum. Similarly, the study will determine whether the presence of PBMC-associated HBV DNA in some "HBV immune" patients is sufficient to permit replication of HDV. Finally, household members of hemophiliacs will be examined for evidence of HBV, HDV and NANB hepatitis infection in order to determine the risk of transmission of these agents in the home environment.