DELTA HEPATITIS AND LIVER DISEASE IN HEMOPHILIACS

慢性肝病被怀疑与5%-11%的 在血友病患者中发生的死亡。乙肝病毒感染的频率 (乙肝病毒)标志在这一人群中没有明显的变化 1975年，对献血者血液进行乙肝表面抗原筛查成为强制性规定。虽然很多人 血友病患者被认为患有非甲非乙型肝炎 他们肝脏疾病的原因，活动性乙肝病毒感染仍占 合理比例的案件。最近，一种新的发现 病毒制剂丁型肝炎病毒(HDV)加深了我们对 慢性肝病的免疫发病机制。独一无二的 HDV的特征是它依赖于乙肝病毒的复制 表情。乙肝患者重叠感染丁型肝炎病毒常导致 一种严重的、最终致命的疾病。正因为如此，有一个不断增长的 令人担忧的是，HDV可能会导致更严重的发展 慢性肝病，见于患有乙肝的血友病患者。 从凝血因子中去除或灭活该病毒的方法 浓缩物，例如通过热灭活，显然还没有 成功。这项建议的长期目标和具体目标 是为了确定一大群血友病患者中HDV的流行率 并阐明HDV在肿瘤的发生发展中的作用。 这一人群中的肝病。将建立活动性HDV感染 通过使用敏感的、非侵入性的血清学技术，最近 已开发出用于检测HDV RNA和AN的HDV RNA/cDNA探针 免疫印迹法检测HDAg。这些测试应该可以避免需要 做肝脏活组织检查以证实HDV感染。纵向研究： 监测肝功能，评估淋巴细胞标志物的变化，以及 评估迟发性超敏反应将有助于确定 乙肝病毒和丁型肝炎病毒的联合感染在临床上是否比 与NANB肝炎或单纯乙肝相关的感染。在场和 血清和外周血单个核细胞中HBVDNA的物理状态 血友病患者外周血单个核细胞(PBMC)的检测将与血清中HDV的检测有关。 同样，该研究将确定是否存在与PBMC相关的 一些“乙肝免疫”患者体内的HBVDNA足以进行复制 人类免疫缺陷病毒。最后，血友病患者的家庭成员将接受检查 乙肝、丁型肝炎和非乙型肝炎的证据以确定 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.