Occult Hepatitis B

描述（由申请人提供）： 该提案的目标是为医学博士Michael Torbenson提供一段时间的指导，使他能够在适当的科学环境中获得必要的技能，成为一名独立的临床科学家。Torbenson博士在诊断肝脏病理学方面有很强的背景，并对病毒性肝炎特别感兴趣。该提案的重点是隐匿性B型肝炎，一种新出现的具有潜在重大医学意义的感染性实体。隐匿性B型肝炎与晚期肝纤维化、丙型肝炎合并感染、丙型肝炎治疗中的IFN α耐药和肝细胞癌相关。Torbenson博士提案的总体目标是评估注射吸毒者高危患者人群中隐匿性B型肝炎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血清和肝组织纵向收集的独特资源，可以评估隐匿性B型肝炎随时间的患病率，并估计这些个体的纤维化进展率。第一个目的是检查隐匿性B型肝炎的总体患病率，并调查人类免疫缺陷病毒状态对隐匿性B型肝炎的影响。第二个目的是通过将隐匿性B型肝炎的存在与肝活检的炎症和纤维化的量相关联来评估隐匿性B型肝炎的临床意义。将通过比较初始肝活检与随访活检的纤维化量来研究纤维化进展率。此外，目标2将检查隐匿性B型肝炎在HIV进展中的作用。第三个目标集中于隐匿性B型肝炎的潜在机制，并寻求确定相关的B型肝炎基因突变。作为这一目标的最后一个要素，将通过分析mRNA和蛋白质表达来研究仔细选择的（基于已知参与典型的B型肝炎病毒感染）信号传导途径，以研究宿主-病毒相互作用。

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.