Changes in Bone Quality, Sarcopenia and Fat Distribution in HIV/HCV Patients after HCV Therapy

项目摘要/摘要 与丙型肝炎病毒(丙型肝炎病毒)混合感染在艾滋病毒感染患者中很常见。艾滋病毒加剧了丙型肝炎病毒- 相关的代谢并发症，合并感染的患者发生骨质疏松症、内脏肥胖症、 肝脏脂肪变性和骨折的患者比单独感染丙型肝炎病毒、单独感染艾滋病病毒或未感染的人更多。重要的是 这些代谢并发症中的每一种都与艾滋病毒+/丙型肝炎+患者的发病率和死亡率有关。 尽管这些异常在艾滋病毒+/丙型肝炎+患者中的高流行率及其对 存活、石棺减少、脂肪改变和骨骼脆性的基础还没有确定。 了解肌肉质量/力量、脂肪质量/分布和骨强度之间的关系 HIV+/丙型肝炎病毒阳性患者，他们与丙型肝炎病毒阳性和非感染者有何不同，以及他们与病毒水平的关系 炎性细胞因子(白介素6和18；肿瘤坏死因子-α)和胰岛素样生长因子-1 将阐明艾滋病毒/丙型肝炎病毒感染与肌肉骨骼健康、脂肪分布以及 炎症的作用。此外，尚不清楚用直接作用抗病毒(DAA)疗法治愈丙型肝炎病毒是否有所改善。 这些异常，以及艾滋病毒+/丙型肝炎病毒+和丙型肝炎病毒+患者的改善程度是否相似。 为了解决这些知识差距，我们将召集三组患者：1)丙型肝炎病毒治疗--幼稚 艾滋病毒+/丙型肝炎+混合感染患者开始DAA治疗，2)治疗-单纯丙型肝炎+单一感染患者 启动DAA治疗，以及3)非感染者。我们将前瞻性地跟踪这两个感染丙型肝炎病毒的队列 丙型肝炎治愈后12个月(18个月)和未感染队列开始DAA治疗 超过18个月。我们假设艾滋病毒和丙型肝炎相关炎症(由白介素6介导， 白介素18、肿瘤坏死因子-α和胰岛素样生长因子-1是体内异常的关键决定因素 人类免疫缺陷病毒/丙型肝炎病毒阳性患者的组成与骨脆性我们进一步假设丙型肝炎病毒的治愈将导致 这些细胞因子的显著减少和IGF-1的增加将导致肌肉的改善 体重/强度、内脏肥胖、肝脏脂肪变性和骨强度，但对于HIV+/丙型肝炎+患者则较少。 目标1将比较肌肉质量(通过双能X射线吸收测量法)，肌肉力量；MRI测量 皮下、内脏和肝内脂肪；以及高分辨率外周骨骼微结构/强度 在登记时对队列进行定量CT，并评估细胞因子和IGF-1作为决定因素 这些结果。目的探讨丙型肝炎病毒(丙型肝炎病毒)经DAA治疗后对细胞因子和IGF-1水平的影响。 HIV+/丙型肝炎病毒阳性和丙型肝炎病毒阳性患者及其与肌肉、脂肪和骨骼随后变化的关系 与同一时间内未感染人群的变化进行比较。这些目标的实现将解决 关于石棺减少、脂肪、炎症细胞因子和胰岛素样生长因子-1等决定因素的关键知识空白 HIV+/HCV+患者的改变和骨骼脆性，提供了关于艾滋病毒/丙型肝炎病毒可逆性的基本信息 丙型肝炎病毒治愈后的异常，并确定肌肉、脂肪和骨骼强度改善的决定因素。

PROJECT SUMMARY/ABSTRACT Coinfection with hepatitis C virus (HCV) is common among HIV infected patients. HIV exacerbates HCV- related metabolic complications, and coinfected patients have a higher risk of sarcopenia, visceral adiposity, hepatic steatosis, and bone fracture than those with HCV alone, HIV alone, or uninfected persons. Importantly, each of these metabolic complications is associated with morbidity and mortality in HIV+/HCV+ patients. Despite the high prevalence of these abnormalities among HIV+/HCV+ patients and their adverse impact on survival, the underpinnings for the sarcopenia, fat alterations, and skeletal fragility have not been established. Understanding the associations among muscle mass/strength, fat mass/distribution, and bone strength in HIV+/HCV+ patients, how they differ from those of HCV+ and uninfected persons, and their relations with levels of inflammatory cytokines (interleukin-6 and -18; tumor necrosis factor-α) and insulin-like growth factor-1 (IGF-1) will shed light on the relations between HIV/HCV infections and musculoskeletal health, fat distribution, and the role of inflammation. Further, it is unknown if cure of HCV with direct-acting antiviral (DAA) therapy ameliorates these abnormalities, and if the degree of improvement is similar for HIV+/HCV+ and HCV+ patients. To address these knowledge gaps, we will assemble three cohorts of patients: 1) HCV treatment-naïve HIV+/HCV+ coinfected patients initiating DAA therapy, 2) treatment-naïve HCV+ monoinfected patients initiating DAA therapy, and 3) uninfected persons. We will prospectively follow both HCV infected cohorts from the start of DAA therapy through 12 months after cure of HCV (18-month period) and the uninfected cohort over 18 months. We hypothesize that HIV and HCV-associated inflammation (mediated by interleukin-6, interleukin-18, and tumor necrosis factor-α) and IGF-1 are key determinants of the abnormalities in body composition and bone fragility in HIV+/HCV+ patients. We further hypothesize that cure of HCV will result in significant decreases in these cytokines and an increase in IGF-1 that will lead to improvements in muscle mass/strength, visceral adiposity, hepatic steatosis, and bone strength, but less so for HIV+/HCV+ patients. Aim 1 will compare muscle mass (by dual-energy X-ray absorptiometry), muscle strength; MRI measures of subcutaneous, visceral, and intra-hepatic fat; and bone microarchitecture/strength by high resolution-peripheral quantitative CT across the cohorts at enrollment and evaluate the cytokines and IGF-1 as determinants of these outcomes. Aim 2 will examine the effect of cure of HCV with DAAs on the cytokine and IGF-1 levels in HIV+/HCV+ and HCV+ patients and their associations with subsequent changes in muscle, fat, and bone compared to changes in uninfected persons over the same time. The completion of these aims will address critical knowledge gaps on the determinants (particularly inflammatory cytokines and IGF-1) of sarcopenia, fat alterations, and skeletal fragility in HIV+/HCV+ patients, yield fundamental information on the reversibility of the abnormalities after cure of HCV, and identify determinants of improvement in muscle, fat, and bone strength.