Occult Hepatitis B

隐匿性乙型肝炎

• 批准号: 6926122
• 负责人: MICHAEL S TORBENSON
• 金额: $ 18.09万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6926122
• 关键词: HIV infections; clinical research; comorbidity; epidemiology; fibrosis; hepatitis B; human data; human tissue; inflammation; intravenous drug abuse; longitudinal human study; pathologic process; virus virus interaction

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.

描述（由申请人提供）： 该提案的目的是为医学博士迈克尔·托宾森（Michael Torbenson）提供一段时间的指导，以便他可以获得必要的技能，成为独立的临床医生。 Torbenson博士在诊断性肝脏病理学方面具有强大的背景，并且对病毒肝炎具有特定的兴趣。该提案着重于隐匿性肝炎，这是一个具有潜在的医学意义的新兴传染病。丙型肝炎与晚期肝纤维化，与丙型肝炎共同感染，IFNα抗性在治疗丙型肝炎中和肝细胞癌。 Torbenson博士提议的总体目的是评估隐匿性乙型肝炎患者在高风险的注射吸毒者群体中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曾经存在的血清和肝组织纵向收集的独特资源，从而评估了随着时间的流逝，这些个体中隐匿性丙型肝炎的患病率以及对这些个体纤维化进展的估计的估计。第一个目的研究了隐匿性丙型肝炎的总体患病率，并研究了人类免疫缺陷病毒状况对隐匿性丙型肝炎的存在的影响。第二目的评估了神秘丙型肝炎的临床意义，通过将神秘性肝炎的存在与炎症和纤维化对肝脏生物的量相关。通过将初始肝活检的纤维化量与随访活检中的纤维化量进行比较，将研究纤维化进展的速率。此外，AIM 2将检查隐匿性丙型肝炎在HIV进展中的作用。第三个目的是隐匿性肝炎的潜在机制，并试图鉴定相关的乙型肝炎基因突变。作为该目标的最终要素，将通过分析mRNA和蛋白质表达来研究仔细选择的（基于已知的典型肝炎病毒感染）信号传导途径，以研究宿主 - 病毒相互作用。