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

HIV/HCV 患者 HCV 治疗后骨质量、肌肉减少症和脂肪分布的变化

• 批准号: 10306385
• 负责人: VINCENT LO RE
• 金额: $ 77.61万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10306385
• 关键词: Address; Adipose tissue; Adverse effects; Antiviral Agents; Antiviral Therapy; Body Composition; Body fat; Bone Density; Chronic; Chronic Hepatitis C; Dual-Energy X-Ray Absorptiometry; Enrollment; Fatty Liver; Fatty acid glycerol esters; Finite Element Analysis; Fracture; Growth Factor; HIV; HIV/HCV; Health; Hepatitis C; Hepatitis C Therapy; Hepatitis C Viremia; Hepatitis C co-infection; Hepatitis C virus; High Prevalence; Hip region structure; Incidence; Inflammation; Inflammatory; Insulin-Like Growth Factor I; Insurance Carriers; Interleukin-18; Interleukin-6; Interleukins; Isotonic Exercise; Knowledge; Leg; Light; Magnetic Resonance Imaging; Measures; Mediating; Metabolic; Morbidity - disease rate; Muscle; Musculoskeletal; Obesity; Outcome; Patients; Peripheral; Persons; Population; Porosity; Recommendation; Resolution; Role; TNF gene; Thick; Thinness; Time; Vertebral column; Viral; Visceral; base; bone; bone fragility; bone health; bone quality; bone strength; clinical practice; co-infection; cohort; cytokine; high risk; improved; insight; intrahepatic; mortality; mortality risk; muscle form; muscle strength; prevent; prospective; radius bone structure; reduced muscle mass; response; sarcopenia; skeletal; subcutaneous; tibia

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.

项目总结/摘要 丙型肝炎病毒（HCV）合并感染在HIV感染者中很常见。HIV会加重HCV- 相关的代谢并发症，并且合并感染的患者具有更高的肌肉减少症，内脏肥胖症， 肝脂肪变性和骨折的发生率高于单纯HCV感染者、单纯HIV感染者或未感染者。重要的是， 这些代谢并发症中的每一种都与HIV+/HCV+患者的发病率和死亡率相关。 尽管这些异常在HIV+/HCV+患者中的发病率很高， 存活率、肌肉减少症、脂肪改变和骨骼脆弱性的基础尚未建立。 了解肌肉质量/强度、脂肪质量/分布和骨强度之间的关系， HIV+/HCV+患者，他们与HCV+和未感染者的区别，以及他们与水平的关系 炎性细胞因子（白细胞介素-6和-18;肿瘤坏死因子-α）和胰岛素样生长因子-1（IGF-1） 将阐明HIV/HCV感染与肌肉骨骼健康、脂肪分布和 炎症的作用。此外，目前还不清楚是否治愈丙型肝炎病毒与直接作用的抗病毒（DAA）治疗改善 这些异常，如果改善程度是类似的HIV+/HCV+和HCV+患者。 为了解决这些知识缺口，我们将收集三个队列的患者：1）HCV初治 启动DAA治疗的HIV+/HCV+合并感染患者，2）未经治疗的HCV+单一感染患者 开始DAA治疗，和3）未感染的人。我们将前瞻性地随访两个HCV感染队列， HCV治愈后12个月内开始DAA治疗（18个月）和未感染队列 超过18个月我们假设HIV和HCV相关的炎症（由白细胞介素-6介导， 白细胞介素-18和肿瘤坏死因子-α）和IGF-1是机体异常的关键决定因素， HIV+/HCV+患者的骨组成和骨脆性。我们进一步假设HCV的治愈将导致 这些细胞因子的显着减少和IGF-1的增加，这将导致肌肉的改善 质量/强度、内脏脂肪过多、肝脂肪变性和骨强度，但HIV+/HCV+患者的情况较少。 目的1将比较肌肉质量（通过双能X线吸收法）、肌肉力量; 皮下、内脏和肝内脂肪;以及通过高分辨率-外周 在入组时对队列进行定量CT，并评估细胞因子和IGF-1作为 这些结果。目的2将检测用DAA治疗HCV对细胞因子和IGF-1水平的影响， HIV+/HCV+和HCV+患者及其与随后肌肉、脂肪和骨骼变化的相关性 与同期未感染者的变化相比。这些目标的实现将解决 关于肌肉减少症的决定因素（特别是炎性细胞因子和IGF-1）的关键知识差距，脂肪 HIV+/HCV+患者的骨骼脆弱性，产生了关于逆转性的基本信息。 HCV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。

项目成果

Strategies for the elimination of hepatitis C virus infection as a public health threat in the United States.

• DOI: 10.1007/s11901-018-0394-x
• 发表时间: 2018-06
• 期刊: Current hepatology reports
• 作者: Gowda C;Lo Re V 3rd
• 通讯作者: Lo Re V 3rd

Determinants of stigma among patients with hepatitis C virus infection.

• DOI: 10.1111/jvh.13343
• 发表时间: 2020-11
• 期刊: JOURNAL OF VIRAL HEPATITIS
• 影响因子: 2.5
• 作者: Saine, M. Elle;Szymczak, Julia E.;Moore, Tyler M.;Bamford, Laura P.;Barg, Frances K.;Schnittker, Jason;Holmes, John H.;Mitra, Nandita;Lo Re, Vincent, III
• 通讯作者: Lo Re, Vincent, III

The impact of disease-related knowledge on perceptions of stigma among patients with Hepatitis C Virus (HCV) infection.

• DOI: 10.1371/journal.pone.0258143
• 发表时间: 2021
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Saine ME;Szymczak JE;Moore TM;Bamford LP;Barg FK;Forde KA;Schnittker J;Holmes JH;Mitra N;Lo Re V 3rd
• 通讯作者: Lo Re V 3rd