Occult Hepatitis B

描述(由申请人提供)： 这项建议的目标是在适当的科学环境中为迈克尔·托本森医学博士提供一段时间的指导，以便他能够获得成为一名独立临床医生兼科学家所需的技能。托本森博士在诊断肝脏病理学方面有很强的背景，对病毒性肝炎特别感兴趣。这项建议的重点是隐匿性乙肝，这是一种具有潜在重大医学意义的新兴传染病。隐匿性乙肝与晚期肝纤维化、丙型肝炎合并感染、治疗丙型肝炎的干扰素耐药和肝细胞癌有关。Torbenson博士建议的总体目标是评估注射吸毒者高危患者人群中隐匿性乙肝的患病率和临床意义。这项研究利用了导师正在进行的研究中预先存在的纵向血清和肝组织的独特资源，从而能够评估随着时间的推移隐匿性乙肝的患病率，并估计这些人的纤维化进展速度。第一个目的是检查隐匿性乙肝的总体流行情况，并调查人类免疫缺陷病毒状态对隐匿性乙肝存在的影响。第二个目的是通过将隐匿性乙肝的存在与肝活检的炎症和纤维化程度相关联来评估隐匿性乙肝的临床意义。肝纤维化进展率将通过比较初次肝活检和后续肝活检的纤维化量来调查。此外，目标2将研究隐匿性乙肝在艾滋病毒进展中的作用。第三个目标集中在隐匿性乙肝的潜在机制上，并试图确定相关的乙肝基因突变。作为这一目标的最后一个要素，将通过分析mRNA和蛋白质的表达来研究精心挑选的信号通路(基于已知参与典型的乙肝病毒感染)，以研究宿主与病毒的相互作用。

DESCRIPTION (provided by applicant): The goal of this proposal is to provide Michael Torbenson, MD with a period of mentorship in the proper scientific environment so that he can acquire the necessary skills to become an independent clinician-scientist. Dr. Torbenson has a strong background in diagnostic liver pathology and has a specific interest in viral hepatitis. This proposal focuses on occult hepatitis B, an emerging infectious entity of potentially large medical significance. Occult hepatitis B has been associated with advanced liver fibrosis, coinfection with hepatitis C, IFN alpha resistance in treatment of hepatitis C, and hepatocellular carcinoma. The overall aim of Dr. Torbenson's proposal is to assess the prevalence and clinical significance of occult hepatitis B in high risk patient population of injection drug users. This study utilizes the unique resources of a pre-existing longitudinal collection of sera and liver tissue from the mentor's ongoing research, allowing assessment of the prevalence of occult hepatitis B over time and estimation of the rate of fibrosis progression in these individuals. The first aim examines the overall prevalence of occult hepatitis B and investigates the impact of Human Immunodeficiency Virus status on the presence of occult hepatitis B. The second aim assess the clinical significance of occult hepatitis B by correlating the presence of occult hepatitis B with the amount of inflammation and fibrosis on liver biopsy. The rate of fibrosis progression will be investigated by comparing the amount of fibrosis on initial liver biopsy to that on follow-up biopsies. In addition, aim 2 will examine the role of occult hepatitis B in HIV progression. The third aim focuses on potential mechanisms of occult hepatitis B and seeks to identify relevant hepatitis B gene mutations. As a final element of this aim, carefully selected (based on known involvement in typical hepatitis B viral infection) signaling pathways will be investigated by analysis of mRNA and protein expression to investigate host-viral interactions.