Mentoring Junior Faculty: Hepatitis C Clinical Research

描述(由申请人提供)： 临床医生在管理慢性丙型肝炎患者方面面临两大挑战。第一，慢性丙型肝炎的自然历史仍然知之甚少，因此我们正在护理的单个患者的病程预测仍然不准确。流行病学研究表明，许多宿主因素，如性别、饮酒和艾滋病毒合并感染，与快速发展的疾病有关。然而，这些相互作用改变疾病发病机制的机制仍不清楚。第二个挑战是试图优化针对不同人群的丙型肝炎患者的治疗方案。尽管治疗丙型肝炎的新疗法越来越有效，但有大量证据表明，某些患者群体对抗病毒治疗的反应不如其他人群。到目前为止，还没有针对这些问题或发生这种情况的机制的前瞻性研究。在我的指导下，北卡罗来纳大学肝病项目目前正在积极开展各种研究，这些研究集中在丙型肝炎的这两个重要主题上。这些研究为积极参与其设计、执行和分析的初级教职员工和研究员提供了指导计划的支柱。在本申请中，我将重点介绍由NIDDK资助的一项涉及特殊人群的正在进行的研究，该研究调查患有慢性丙型肝炎的非裔美国人的抗病毒反应和耐药性(UO1-DK60327-01，VIRAHEP-C)。我还将提供其他正在进行的研究的概要，这些研究构成了我们的丙型肝炎研究计划的核心。我的直接职业目标是在北卡罗来纳大学保持以患者为中心的研究轨迹。从长远来看，我希望领导一个由临床研究人员和基础科学家组成的多学科团队，他们可以在慢性病毒性肝炎发病机制的翻译研究方面密切合作。最后，我在综合临床研究中心(GCRC)的工作经历非常有利，我希望更积极地参与到这个项目中来。K-24奖将允许我通过解除我的一些临床承诺来实现我的目标，从而使我能够进一步专注于以患者为导向的研究。它将为我提供更多的时间来指导初级教员和研究员，并继续在蓬勃发展的以患者为导向的研究计划的背景下促进他们的发展。

DESCRIPTION (provided by applicant): Clinicians face two major challenges in managing patients with chronic hepatitis C. First, the natural history of chronic hepatitis C remains poorly understood so that predicting the course for an individual patient for whom we are caring remains imprecise. Epidemiologic studies have implicated a number of host factors, such as gender, alcohol consumption, and HIV co-infection, as being associated with rapidly progressive disease. However, the mechanisms by which these interact to alter disease pathogenesis remain unknown. The second challenge is trying to optimize therapy for a diverse population of patients infected with hepatitis C. Although newer therapies for HCV are increasingly effective, there is a large body of evidence to suggest that certain patient populations respond less well to antiviral therapy than others. To date, there have been no prospective studies addressing these issues or the mechanisms by which this may occur. The UNC Liver Diseases Program, under my direction, is currently active in pursuing various studies that focus on these two important themes in hepatitis C. These studies provide the backbone of my mentoring program for junior faculty and fellows who are actively involved in their design, execution, and analysis. For the purposes of this application, I will focus on one ongoing study involving special populations, funded by NIDDK, that investigates antiviral response and resistance in African Americans with chronic hepatitis C (UO1-DK60327- 01, VIRAHEP-C). I will also provide a synopsis of other ongoing studies that form the core of our HCV research program. My immediate career goal is to maintain the trajectory of patient-oriented research at UNC. In the long-term, I would like to direct a multi-disciplinary team of clinical investigators and basic scientists who can work together closely on translational studies of the pathogenesis of chronic viral hepatitis. Finally, my experiences working within the General Clinical Research Center (GCRC) have been very favorable and I would like to become more actively involved in that program. The K-24 award will allow me to attain my goals by relieving me of some of my clinical commitments, thus allowing me to concentrate further on patient-oriented research. It will provide me with additional time to mentor junior faculty and fellows and continue to foster their development within the context of a burgeoning patient-oriented research program.