Mentoring Junior Faculty: Viral hepatitis Clinical Research

描述(申请人提供)：慢性病毒性肝炎是全球发病率和死亡率的主要原因。在过去的十年里，慢性丙型肝炎和乙肝的新治疗方法的开发取得了重大进展，尽管这些疾病的管理策略仍在不断演变。接受聚乙二醇干扰素和利巴韦林治疗的慢性丙型肝炎患者中，超过一半的人可以实现持续的病毒学应答。然而，许多患者仍然无法实现永久的病毒根除，或者由于内科或心理社会并存而不适合接受初始抗病毒治疗，这是聚乙二醇干扰素和利巴韦林治疗的禁忌症。相比之下，使用核苷类似物治疗慢性乙肝的耐受性更好，尽管疗效通常是通过延长病毒抑制时间来衡量的，而不是永久治愈。对于这两种疾病，更好地了解治疗反应减弱的机制，开发优化的治疗方案，和/或确定替代或新的药物是至关重要的。北卡罗来纳大学肝病项目在迈克尔·弗里德博士的指导下，非常积极地开展以慢性病毒性肝炎治疗为重点的研究。在本申请中，我们将讨论由NCCAM/NIDDK资助的一项正在进行的I/II阶段研究，该研究调查水飞蓟素(牛奶蓟)作为传统抗病毒治疗无效的慢性丙型肝炎患者的替代疗法(U01-AT003560，SYNCH)。此外，我们还将回顾由NIDDK(U01 DK082867)资助的一项新的慢性乙型肝炎研究--乙肝临床研究网络。最后，我们将提供研究人员发起的一项研究的详细概要，该研究使用新的方法检查外周血单核细胞中的干扰素信号通路。这些研究为积极参与其设计、实施和分析的初级教员和研究员提供了指导计划的支柱。如本申请所示，被辅导者已融入这些研究活动，这为他们在指导环境中发展研究技能和维护他们对个别项目的所有权提供了许多机会。 公共卫生相关性：在K24导师奖的竞争续签申请中，我将详细介绍我在以患者为导向的研究方面的背景，以及作为该奖项的直接结果而直接开发的成功的临床研究和综合导师计划。我还将继续致力于临床研究，并向我担任主要导师的一群有才华的初级调查人员展示我的持续奉献精神。最后，我们将提供几个新的研究倡议的例子，这些新的研究倡议将继续确保有效的指导研究机会，以及发展能够进行转化性研究的跨学科研究团队的计划。

DESCRIPTION (provided by applicant): Chronic viral hepatitis is a major global cause of morbidity and mortality. Over the last decade, significant progress has occurred in the development of new treatments for chronic hepatitis C and hepatitis B, although management strategy of these diseases continues to evolve. More than half of patients undergoing treatment with peginterferon and ribavirin for chronic hepatitis C can achieve a sustained virological response. However, numerous patients still fail to achieve permanent viral eradication or are not candidates for initial antiviral therapy due to medical or psychosocial comorbidities which are contraindications to peginterferon and ribavirin therapy. In contrast, treatments for chronic hepatitis B with nucleoside analogues, as examples, are better tolerated, although efficacy is generally measured by prolonged viral suppression, rather than permanent cure. For both these diseases, a better understanding of mechanisms of diminished response to therapy, development of optimized treatment regimens, and/or the identification of alternative or novel medications is of critical importance. The UNC Liver Diseases Program, under the direction of Dr. Michael Fried, is extremely active in pursuing studies that focus on treatment of chronic viral hepatitis. For the purposes of this application, we will discuss an ongoing phase I/II study, funded by NCCAM/NIDDK, that investigates silymarin (milk thistle) as an alternative treatment for patients with chronic hepatitis C who failed to respond to conventional antiviral therapy (U01-AT003560, SyNCH). Furthermore, we will review a new study for chronic hepatitis B, the Hepatitis B Clinical Research Network, funded by NIDDK (U01 DK082867). Finally, we will present a detailed synopsis of an investigator initiated study that examines interferon signaling pathways in peripheral blood mononuclear cells utilizing novel methodologies. These studies provide the backbone of the mentoring program for junior faculty and fellows who are actively involved in their design, implementation, and analysis. As demonstrated within this application, mentees have been integrated into these research activities which have provided them with numerous opportunities in a mentored environment within which to develop research skills and to assert their ownership of individual projects. PUBLIC HEALTH RELEVANCE: In this competing renewal application for the K24 Mentoring Award, I will provide detailed information regarding my background in patient-oriented research and the successful clinical research and integrated mentoring program that has been developed directly as a result of this award. I will also demonstrate my continued dedication to clinical research and to a diverse group of talented junior investigators for whom I serve as primary mentor. Finally, we will provide examples of several new research initiatives that will continue to ensure effective mentored research opportunities, as well as a plan for the development of interdisciplinary research teams capable of performing translational research studies.