The Impact of HCV Infection on Bone Turnover, Density, and Strength

 描述（由申请方提供）：本提案的总体目标是确定丙型肝炎病毒（HCV）感染是否改变骨代谢并导致骨脆性。多项流行病学研究表明，HCV感染与骨折风险增加数倍相关，无论是在HCV单一感染还是HIV/HCV合并感染的患者中。然而，目前尚不清楚这种骨折风险的增加是由于HCV感染本身，与HCV感染相关的行为因素，还是慢性肝病的后果。以往研究的另一个主要局限性是双能X线骨密度仪（DXA）的常规骨密度（BMD）一直是主要的结局指标。然而，DXA的BMD仅解释了约50%的骨折风险。较新的模式，如定量计算机断层扫描（QCT）和参考点压痕可以提供额外的信息，通过测量骨强度和骨质量的差异，超过传统的DXA骨健康。通过使用两个独立的NIH资助的研究作为平台，该项目利用约翰霍普金斯临床HCV研究的优势，并提出补充方法来回答HCV感染本身是否影响骨骼健康的问题。建议的目标如下：1）确定用直接作用抗病毒药物（DAA）成功治疗HCV是否导致HIV/HCV合并感染（Aim 1A）和HCV单一感染患者（Aim 1B）的骨转换改变和BMD改善，2）确定慢性HCV感染对骨密度、强度、和质量，并评估治疗和未治疗的HIV感染对骨结果的附加作用。最近，可以治愈大多数患者的HCV的高效口服治疗已经变得可用，但是治疗成本很高。HCV感染影响骨转换、骨密度和骨强度的发现将为扩大治疗指南提供令人信服的依据，使其超越肝纤维化，并将骨质疏松症作为HCV的肝外表现，应考虑治疗。此外，这些研究将确定哪些方面的骨骼最受慢性HCV感染的影响，以及HIV及其治疗如何增加HIV/HCV合并感染的骨折风险。通过这种方式，将更好地了解HIV和HCV中骨病的发病机制，并更好地了解未来的预防和治疗策略。

 DESCRIPTION (provided by applicant): The overall goal of this proposal is to determine whether hepatitis C virus (HCV) infection alters bone metabolism and leads to bone fragility. Multiple epidemiologic studies have shown that HCV infection is associated with a several fold increased risk of fracture, both in those with HCV monoinfection and HIV/HCV coinfection. However, it is unclear whether this increased fracture risk is due to HCV infection itself, behavioral factors associated with HCV infection, or the consequences of chronic liver disease. Another major limitation of previous studies is that conventional bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) has been the primary outcome measure. However, BMD by DXA only explains about 50% of fracture risk. Newer modalities, such as quantitative computed tomography (QCT) and reference point indentation can provide additional information about bone health beyond conventional DXA by measuring differences bone strength and bone quality. By using two separate NIH-funded studies as a platform, this project leverages the strength of clinical HCV research at Johns Hopkins and proposes complementary approaches to answer the question of whether HCV infection itself impacts bone health. The following aims are proposed: 1) To determine whether successful HCV treatment with direct-acting antivirals (DAA) leads to changes in bone turnover and improved BMD in HIV/HCV coinfected (Aim 1A) and HCV monoinfected patients (Aim 1B), 2) To determine the effect of chronic HCV infection on measures of bone density, strength, and quality using state of the art imaging methodologies and to assess the added effect of treated and untreated HIV infection on bone outcomes. Highly effective, oral treatments which can cure HCV in the majority of patients have recently become available, but the cost of treatment is high. A finding that HCV infection impacts bone turnover, density, and strength would provide a compelling basis for expanding treatment guidelines beyond liver fibrosis and include osteoporosis as an extra-hepatic manifestation of HCV for which treatment should be considered. In addition, these studies will determine which aspects of bone are most affected by chronic HCV infection and how HIV and its treatment may add to fracture risk in HIV/HCV co- infection. In this way, the pathogenesis of bone disease in HIV and HCV will be better understood and future prevention and treatment strategies will be better informed.