HIV, HCV and the Menopausal Transition: Effects on Steatosis and Fibrosis Progression

HIV、HCV 和绝经过渡：对脂肪变性和纤维化进展的影响

• 批准号: 9913999
• 负责人: Phyllis C Tien
• 金额: $ 68.3万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9913999
• 关键词: Acceleration; Address; Adipose tissue; Affect; Age; Area; Cause of Death; Central obesity; Cessation of life; Computer software; Cross-Sectional Studies; Development; Disease Progression; Estrogens; Fatty Liver; Fibrosis; Goals; HIV; HIV Infections; HIV/HCV; Hepatitis C; Hepatitis C co-infection; Hepatitis C virus; High Prevalence; Hormonal Change; Infection; Infection Control; Inflammation; Integration Host Factors; Intestinal permeability; Liver; Liver Fibrosis; Liver diseases; Measures; Menopause; Metabolic; Patient Self-Report; Patients; Persons; Phase; Premature Menopause; Premenopause; Prospective Studies; Reporting; Research; Risk; Risk Factors; Role; Site; Testing; Viral hepatitis; Woman; Women’s Interagency HIV Study; attenuation; co-infection; early onset; elastography; inflammatory disease of the intestine; men; microbial; mullerian-inhibiting hormone; multidisciplinary; non-alcoholic fatty liver disease; ovarian reserve; public health relevance; sex

 DESCRIPTION (provided by applicant): Liver disease is a leading cause of non‐AIDS‐ related death in HIV‐infected men and women. While coinfection with HCV is a common cause of liver disease, 25‐44% of all liver‐related deaths occurs in HIV‐ monoinfected persons and may be related to non‐alcoholic fatty liver disease (NAFLD) or hepatic steatosis. NAFLD is common in HIV‐infected persons, but the factors associated with its progression and its role in liver fibrosis progression remains elusive. Women now represent about 25% of all HIV‐infected persons in the US. HIV‐infected women are living longer and many are transitioning to menopause. Both HIV and HCV infection are associated with early menopause; HIV/HCV coinfection may be associated with even earlier onset of menopause. Cross‐sectional studies indicate that menopause is associated with a higher prevalence of steatosis, but there are no studies of progression. Visceral obesity and metabolic perturbations increase during the menopausal transition and are risk factors for steatosis. The hormonal changes that characterize menopause may induce inflammation through increased gut permeability. HIV infection is also associated with gut microbial translocation and inflammation, as well as changes in metabolic parameters. We hypothesize that the menopausal transition will accelerate steatosis and fibrosis progression especially in HIV/HCV‐coinfected women, who will have longer cumulative effects of visceral obesity and systemic inflammation from gut microbial translocation due to earlier onset of menopause. In order to test our hypothesis, we propose a prospective study that leverages the research platform provided by the Women's Interagency HIV Study. The first Aim will examine the effects of the menopausal transition and its onset on steatosis progression in women with HIV, HCV, and neither infection. The second Aim will investigate the effects of visceral obesity and gut‐associated microbial translocation o steatosis progression during the menopausal transition in women with HIV, HCV, and neither infection. The third Aim will determine the effects of the menopausal transition and its onset on fibrosis progression in women. In a prior cross‐sectional study in three WIHS sites, we established the use of transient elastography (TE) to measure fibrosis. With the addition of new Continuous Attenuation Parameter software to TE, we will be able to quantify steatosis and fibrosis simultaneously to address our aims in 1,650 women with HIV monoinfection, HIV/HCV coinfection, HCV monoinfection, and neither infection. We will also measure Anti‐Mullerian Hormone (AMH) levels which yield a better estimate of ovarian reserve and thus estrogen depletion than self‐report of menopause. This study will lead to: 1) new information about how menopause affects steatosis and fibrosis progression in the context of HIV, HCV and neither infection; 2) provide quantitative, longitudinal assessments of steatosis and fibrosis, in patients at risk for progression; and 3) inform the development and optimal timing of focused sex‐ and age‐specific approaches to steatosis and fibrosis in HIV and HCV‐infected women.

 描述（由适用提供）：肝病是艾滋病毒感染的男性和女性无关死亡的主要原因。虽然与HCV的共同感染是肝病的常见原因，但所有与肝脏相关的死亡中有25-44％发生在HIV单感染的人中，可能与非酒精性脂肪肝病（NAFLD）或肝炎脂肪变性有关。 NAFLD在受艾滋病毒感染者中很常见，但是与其进展及其在肝纤维化进展中的作用相关的因素仍然难以捉摸。现在，妇女占美国所有艾滋病毒感染者的25％。感染艾滋病毒的妇女的寿命更长，许多人正在过渡到更年期。艾滋病毒和HCV感染都与早期更年期有关。 HIV/HCV共感染可能与更年期的更早发作有关。横断面研究表明，更年期与较高的脂肪变性有关，但没有进展研究。绝经期间内脏肥胖和代谢扰动增加，是脂肪变性的危险因素。更年期特征的马变化可能会通过增加肠道渗透性引起炎症。 HIV感染还与肠道微生物翻译和感染以及代谢参数的变化有关。我们假设绝经过渡将加速脂肪变性和纤维化进展，尤其是在艾滋病毒/HCV生产的妇女中，由于牙科观察和全身感染的累积影响更长，因为肠道微生物翻译而引起的全身感染。为了检验我们的假设，我们提出了一项前瞻性研究，该研究利用了妇女间艾滋病毒研究平台。第一个目的将研究更年期过渡的影响及其对艾滋病毒，HCV女性且既不感染的女性的脂肪变性进展的影响。第二个目标将研究内脏肥胖和与肠道相关的微生物易位O脂肪变化在更年期过渡期间HIV，HCV和既不感染的女性。第三个目标将决定更年期过渡的影响及其对女性纤维化进展的影响。在先前在三个WIHS站点进行的横截面研究中，我们确定了瞬时弹性图（TE）的使用来测量纤维化。通过将新的连续衰减参数软件添加到TE中，我们将能够量化脂肪变性和纤维化，只是为了解决1,650名HIV单感染，HIV/HCV共感染，HCV单感染，既没有感染的目标又解决我们的目标。我们还将测量抗乳房激素（AMH）水平，该水平比对绝经的自我报告更好地估计了卵巢储备，因此可以更好地估计卵巢储备。这项研究将导致：1）有关更年期如何影响脂肪变性和纤维化进展的新信息，而HIV，HCV且既不感染又不感染； 2）对患者进行脂肪变性和纤维化的定量，纵向评估 有进步的风险； 3）为艾滋病毒和HCV感染的妇女的脂肪变性和纤维化的聚焦性和年龄特异性方法的发展和最佳时机提供信息。