Association Between Viral Hepatitis Infection and Low Muscle Mass Among HIV-Positive Individuals

 描述（由申请人提供）：该奖项将为申请人提供作为传染病流行病学家继续发展所需的重要技能，重点是HIV感染者病毒性肝炎的营养和临床结果。拟议的培训计划包括：1）宾夕法尼亚大学临床流行病学和生物统计学中心的高级流行病学课程; 2）来自艾滋病毒，病毒性肝炎和营养方面成功研究人员的指导; 3）与两项正在进行的艾滋病毒队列研究的研究人员合作。B型肝炎病毒（HBV）和丙型肝炎病毒（HCV）感染在HIV感染者中非常普遍，病毒性肝炎导致的疾病进展加速导致这些患者的发病率和死亡率。确定合并感染患者加速疾病进展和不良结局的潜在机制对于制定有针对性的治疗策略至关重要。艾滋病毒感染者的营养不良已被证明是健康状况不佳的一个独立风险因素，外周肌肉质量的损失往往是营养不良的最初指标。重要的是，慢性病毒性肝炎合并感染也可能引起患者营养状况的不良变化，并进一步导致低肌肉质量的发展，除了HIV和肝失代偿发作之前。因此，低肌肉质量可能是病毒性肝炎和艾滋病毒合并感染者健康状况不佳的重要因素。然而，关于这些患者发生低肌肉质量的数据很少。为了开始缩小知识差距，本提案寻求：1）确定HBV或HCV感染是否与HIV感染患者的低肌肉质量相关; 2）确定合并感染患者低肌肉质量的风险因素。据推测，合并感染的患者将有一个更高的患病率低肌肉质量相比，艾滋病毒单一感染和未感染的人。低肌肉质量的潜在风险因素包括肝脏炎症、HIV疾病严重程度、物质使用、代谢综合征和/或慢性肾脏疾病。这些目标将通过妇女机构间艾滋病毒研究和多中心艾滋病队列研究内的横断面分析来实现，这两项研究都是正在进行的艾滋病毒感染者前瞻性队列研究。病毒性肝炎和肌肉质量损失之间的关联表明，临床医生应该筛查合并感染的低肌肉质量患者。这项工作将通过确定可能改善艾滋病毒/病毒性肝炎合并感染患者生存结局的可改变的宿主因素，特别是在资源有限的情况下，获得有限的抗病毒治疗或移植，对公共卫生产生重要影响。在完成这些目标后，主要研究者将对病毒性肝炎的营养影响有深入的了解，并准备在病毒性肝炎和营养流行病学方面做出进一步的实质性贡献。

 DESCRIPTION (provided by applicant): This award will provide the applicant with important skills necessary for her continued development as an Infectious Diseases epidemiologist, with a focus on nutritional and clinical outcomes of viral hepatitis in HIV- infected persons. The proposed training plan includes: 1) advanced epidemiologic coursework at the Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania; 2) mentorship from successful researchers in HIV, viral hepatitis and nutrition; and 3) collaboration with investigators from two ongoing HIV cohort studies. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are highly prevalent among individuals with HIV, and accelerated disease progression from viral hepatitis contributes to the morbidity and mortality observed in these patients. Identifying mechanisms underlying the accelerated disease progression and adverse outcomes in coinfected patients is critical to developing targeted therapeutic strategies. Malnutrition in HIV-infected patients has been shown to be an independent risk factor for poor health outcomes, with loss of peripheral muscle mass often an initial indicator of poor nutrition. Importantly, coinfection with chronic viral hepatitis may also induce adverse changes in a patient's nutritional status and further contribute to the development of low muscle mass, apart from HIV and prior to the onset of hepatic decompensation. Thus, low muscle mass may be an important mediator of poor health outcomes among individuals coinfected with viral hepatitis and HIV. However, there are few data on the occurrence of low muscle mass in these patients. To begin to close the knowledge gap, this proposal seeks to: 1) determine if HBV or HCV infection is associated with low muscle mass among HIV-infected patients; and 2) identify risk factors for low muscle mass in coinfected patients. It is hypothesized that coinfected patients wil have a higher prevalence of low muscle mass compared to HIV-monoinfected and uninfected persons. Potential risk factors for low muscle mass include hepatic inflammation, HIV disease severity, substance use, metabolic syndrome and/or chronic kidney disease. The aims will be accomplished through a cross-sectional analysis within the Women's Interagency HIV Study and Multicenter AIDS Cohort Study, both of which are ongoing, prospective cohorts of HIV-infected persons. An association between viral hepatitis and loss of muscle mass would indicate that clinicians should screen coinfected patients for low muscle mass. This work will have important public health impact by identifying modifiable host factors that may improve survival outcomes among HIV/viral hepatitis-coinfected patients, particularly in resource-constrained settings with limited access to antiviral therapy or transplantation. Upon completion of these aims, the principal investigator will have advanced understanding of the nutritional impact of viral hepatitis and be poised to make further substantive contributions in viral hepatitis and nutritional epidemiology.