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时面临两大挑战。首先，慢性丙型肝炎的自然史仍然知之甚少，因此预测我们所关心的个体患者的病程仍然不准确。流行病学研究表明，许多宿主因素，如性别、饮酒和HIV合并感染，与疾病的快速进展有关。然而，这些相互作用以改变疾病发病机制的机制仍然未知。第二个挑战是试图为感染丙型肝炎的不同人群优化治疗。虽然HCV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。到目前为止，还没有前瞻性研究解决这些问题或可能发生的机制。在我的指导下，肝病项目目前正在积极开展各种研究，重点关注丙型肝炎的这两个重要主题。这些研究为我的指导计划提供了支柱，这些指导计划针对的是积极参与设计、执行和分析的初级教师和研究员。出于本申请的目的，我将重点关注一项由NIDDK资助的涉及特殊人群的正在进行的研究，该研究调查了非裔美国人慢性丙型肝炎患者的抗病毒反应和耐药性（UO 1-DK 60327 - 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HCV研究计划的核心。我的近期职业目标是在斯坦福大学保持以患者为导向的研究轨迹。从长远来看，我想指导一个多学科的临床研究人员和基础科学家团队，他们可以在慢性病毒性肝炎发病机制的转化研究上密切合作。最后，我在综合临床研究中心（GCRC）的工作经历非常有利，我想更积极地参与该计划。K-24奖将使我能够通过减轻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。这将为我提供更多的时间来指导初级教师和研究员，并继续促进他们的发展范围内的一个新兴的以病人为导向的研究计划。

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.