HIV status and reproductive aging affect liver fibrosis in HIV/HCV infected women

HIV 状况和生殖衰老影响 HIV/HCV 感染女性的肝纤维化

• 批准号: 8044193
• 负责人: MARION G PETERS
• 金额: $ 20.44万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-15 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8044193
• 关键词: Address; Admission activity; Affect; Age; Aging; Anti-Retroviral Agents; Characteristics; Child; Cirrhosis; Clinical; Clinical Data; Cohort Studies; Data; Disease; Disease Progression; Female; Fibrosis; Gender; Gonadal Steroid Hormones; Grant; HCV Liver Disease; HIV; Hepatic; Hepatitis C; Hepatitis C virus; Hospitals; Immunologics; Individual; Infection; Injury; Interferons; Length; Letters; Liver Fibrosis; Liver diseases; Menopause; Mono-S; Morbidity - disease rate; Ovarian; Patients; Persons; Production; Recovery; Research Infrastructure; Research Personnel; Resources; Ribavirin; Risk Factors; Role; Serum; Severities; Severity of illness; Sex Characteristics; Specimen; Variant; Viral; Viral Load result; Virus; Virus Diseases; Visit; Woman; antiretroviral therapy; cofactor; cohort; follow-up; handicapping condition; men; mortality; older women; prospective; public health relevance; reproductive; sex; standard of care; transmission process; viral liver disease

DESCRIPTION (provided by applicant): Coinfection with hepatitis C (HCV) is common in individuals with the human immunodeficiency virus (HIV) because of shared risk factors and modes of transmission. Following the introduction of combination antiretroviral therapy, HCV infection has emerged as one of the most important causes of morbidity and mortality in HIV-infected individuals. Complications of liver disease are now leading reasons for hospital admission among HIV infected patients. Liver disease appears to be accelerated in HIV/HCV coinfected persons. However the severity of hepatic disease is highly variable, even in persons who share HCV viral characteristics, duration of infection, age and gender. The factors responsible for variability in disease course have not been fully elucidated. Most studies of HIV/HCV patients show that coinfection leads to more progressive liver disease than HCV alone but men predominate in these studies and information on women is needed since sex differences are recognized in HCV and other viral liver diseases. Women and children infected with HCV alone clear the virus at a higher rate than men, and develop liver disease at a slower rate and with fewer cases of cirrhosis. The rate of progression of liver fibrosis in women who are coinfected with HIV and HCV is not known. Progression in dually infected women may be more rapid than among those with HCV mono-infection and yet be slower than in men coinfected with HIV/HCV. The advantages of female sex, if they exist, may be lost at menopause, when production of ovarian sex steroids ceases. This study will address the critical issue of fibrosis progression in HIV/HCV coinfection among women, and the impact of menopause on this progression. We hypothesize that women with HIV and HCV will have variable fibrosis progression of liver disease related to HIV status. We further hypothesize that the rate of fibrosis will increase, coincident with completion of the menopausal transition, indicating that any sex advantage in hepatic disease will disappear in older women. This grant will utilize the established research infrastructure for longitudinal follow-up of subjects in WIHS and the availability of results from clinical data, HIV and HCV data as well as from stored biologic specimens, will serve as a platform for cutting-edge collaborative studies. The WIHS is a unique resource for addressing these aims. PUBLIC HEALTH RELEVANCE: This proposal will study the progression of liver disease in women with HIV and hepatitis C coinfection to determine the host and viral cofactors which predict progression of disease. There is great variation in the severity of disease, even in subjects with similar HCV viral characteristics, length of infection, age and gender. The causes of this variation are not fully elucidated. Most studies of patients coinfected with HIV and HCV show that coinfection leads to more progressive liver disease than HCV alone but men predominate in these cohorts. Women and children infected with HCV alone clear the virus at a higher rate than men, develop less progression of liver disease culminating in fewer cases of cirrhosis than men but the rate of progression of liver fibrosis in women co-infected with HIV and HCV is not known. We will determine the role of menopause and HIV in progression of liver disease in HIV/HCV co-infected women. This will have important consequences as women with mild or no liver fibrosis are not recommended for current therapy while those with significant fibrosis should be treated with pegylated interferon and ribavirin, the standard of care for HCV and HIV infected patients.

描述（由申请人提供）：与丙型肝炎（HCV）共同感染在人类免疫缺陷病毒（HIV）的个体中很常见，因为共同的风险因素和传播方式。在引入抗逆转录病毒疗法的联合疗法之后，HCV感染已成为HIV感染者发病和死亡率最重要的原因之一。肝病的并发症现在是HIV感染患者入院的主要原因。肝病似乎在HIV/HCV共感染的人中加速了。但是，即使在具有HCV病毒特征，感染持续时间，年龄和性别的人中，肝病的严重程度也很大。导致疾病病程变异性的因素尚未完全阐明。大多数对HIV/HCV患者的研究表明，与单独使用HCV相比，共同感染会导致肝病的进行性肝脏疾病更多，但是在这些研究中，男性占主导地位，并且需要有关女性的信息，因为在HCV和其他病毒肝病中认识到性别差异。单独感染HCV的妇女和儿童比男性更高的病毒清除病毒，并以较慢且肝硬化病例较少而发展肝病。与HIV和HCV共同感染的女性肝纤维化进展率尚不清楚。双重感染女性的进展可能比HCV单感染的女性更快，但比与HIV/HCV共同感染的男性慢。当卵巢性类固醇的产生停止时，女性的优势（如果存在）可能会在更年期失去。这项研究将解决女性HIV/HCV共同感染中纤维化进展的关键问题，以及更年期对这种进展的影响。我们假设患有HIV和HCV的女性将具有与HIV状况有关的肝病的纤维化进展。我们进一步假设，纤维化的速率将增加，这与绝经期的过渡结束相一致，这表明肝病中的任何性别优势都会在老年妇女中消失。该赠款将利用既定的研究基础设施来对WIHS中受试者的纵向随访以及临床数据，HIV和HCV数据以及存储的生物标本的结果，将作为切割边缘协作研究的平台。 WIHS是解决这些目标的独特资源。 公共卫生相关性：该提案将研究艾滋病毒和丙型肝炎女性肝病的进展，以确定预测疾病进展的宿主和病毒辅助因子。即使在具有相似HCV病毒特征，感染长度，年龄和性别的受试者中，疾病的严重程度也有很大差异。这种变化的原因未完全阐明。与HIV和HCV共同感染的大多数患者的研究都表明，与单独HCV相比，共感染会导致更多的进行性肝脏疾病，但男性在这些队列中占主导地位。单独感染HCV的妇女和儿童比男性更高的病毒清除病毒，在肝硬化较少的情况下，肝病的进展低于男性，但与HIV和HCV共同感染的女性中肝纤维化进展的速度尚不清楚。我们将确定更年期和HIV在肝病进展中的作用在艾滋病毒/HCV共感染的妇女中。这将带来重要的后果，因为不建议使用轻度或无肝纤维化的女性进行当前治疗，而患有明显的纤维化的女性应使用pegyperated干扰素和利巴韦林进行治疗，这是HCV和HIV感染患者的护理标准。