Risk factors and prediction of liver disease in HIV/HCV

HIV/HCV 肝病的危险因素和预测

• 批准号: 7596931
• 负责人: VINCENT LO RE
• 金额: $ 13.3万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-15 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7596931
• 关键词: Address; Aging; Alcohol consumption; Award; Binding; Biometry; Blood Coagulation Disorders; Caring; Chronic Hepatitis C; Clinical; Cohort Studies; Collaborations; Confidence Intervals; Data; Disease Progression; Doctor of Philosophy; Epidemiologist; Epidemiology; Future; HIV; HIV Seropositivity; Hepatitis C; Hepatitis C virus; High Prevalence; Infection; Infectious Disease Epidemiology; Knowledge; Laboratories; Liver diseases; Medical center; Mentorship; Morbidity - disease rate; Natural History; Outcome; Patients; Pharmacy facility; Predictive Value; Principal Investigator; Publishing; Research Personnel; Risk; Risk Factors; Site; Specific qualifier value; Staging; Training; United States Department of Veterans Affairs; Veterans; Virus Diseases; Woman; career; clinical epidemiology; clinical practice; clinically relevant; disorder risk; indexing; liver biopsy; men; mortality; prospective; sex

DESCRIPTION (provided by applicant): This award will prepare the principal investigator for a career as an independent investigator in Infectious Disease epidemiology, with a particular focus on the clinical outcomes of hepatitis C virus (HCV) infection in those co-infected with HIV. The training component of this proposal will include: 1) advanced epidemiologic coursework at the Center for Clinical Epidemiology and Biostatistics at Penn leading to a Ph.D. in Epidemiology, 2) mentorship from an internationally recognized epidemiologist, 3) collaboration with researchers at Penn in HIV epidemiology, chronic HCV infection, and biostatistics, and 4) collaboration with investigators from two ongoing HIV cohort studies. HCV co-infection is highly prevalent among HIV-infected patients, and end-stage liver disease (ESLD), the main clinical outcome of HCV infection, now represents the major cause of morbidity and mortality among HIV patients in the developed world. Despite the high prevalence of HIV/HCV co-infection and impact of ESLD, the risk factors for this clinical outcome have not been well examined among HIV/HCV patients. Published studies have evaluated primarily predictors of histological outcomes, but few HIV/HCV patients undergo liver biopsy because they refuse or are not offered due to contraindications (e.g., active alcohol use or coagulopathy). These studies are therefore unable to determine accurately the true effects of relevant risk factors for liver disease progression among HIV/HCV patients. In contrast, studies focused on a clinical outcome such as ESLD are far preferable because they can include the typical patients with HIV/HCV co-infection. Since data show that liver disease progression is substantially slower in women versus men, the risk factors and predictors of ESLD are likely to be different in HIV/HCV-co-infected women than in men and should be examined separately. To begin to address these issues, this proposal has three Specific Aims: 1) To determine the risk factors for ESLD among HIV/HCV-co-infected men, 2) To derive and internally validate a clinical predictive index to stratify HIV/HCV-co-infected men by risk of progression to ESLD, and 3) To validate the ability of specified combinations of clinical, laboratory, and pharmacy data collected by the Women's Interagency HIV Study to identify HIV/HCV-co-infected women with ESLD. Specific Aims 1 and 2 will utilize data from the Veterans Aging Cohort Study, a multi-center, prospective cohort study of HIV-positive and -negative veterans in care at eight Veterans Administration medical centers. Specific Aim 3 will utilize data from three sites in the Women's Interagency HIV Study, a prospective cohort study of HIV-positive and -negative women. Upon completion of these aims, the PI will have made substantive contributions to knowledge of the natural history and risk factors for HCV co-infection in HIV-infected men and be poised to make similar contributions in the future to knowledge of the natural history of HCV co-infection in HIV-infected women.

描述（由申请人提供）：该奖项将为主要研究者作为传染病流行病学独立研究者的职业生涯做好准备，特别关注丙型肝炎病毒（HCV）感染在合并感染HIV的患者中的临床结果。该建议的培训内容包括：1）在宾夕法尼亚大学临床流行病学和生物统计学中心学习高级流行病学课程，获得博士学位。在流行病学，2）从国际公认的流行病学家的指导，3）在艾滋病毒流行病学，慢性丙型肝炎病毒感染和生物统计学在宾夕法尼亚大学的研究人员合作，和4）从两个正在进行的艾滋病毒队列研究的研究人员合作。HCV合并感染在HIV感染患者中非常普遍，而终末期肝病（ESLD）是HCV感染的主要临床结局，现在是发达国家HIV患者发病和死亡的主要原因。尽管HIV/HCV合并感染的高患病率和ESLD的影响，这种临床结果的危险因素尚未得到很好的检查HIV/HCV患者。已发表的研究主要评估了组织学结局的预测因素，但很少有HIV/HCV患者接受肝活检，因为他们拒绝或因禁忌症（例如，主动饮酒或凝血障碍）。因此，这些研究无法准确确定HIV/HCV患者中肝脏疾病进展相关风险因素的真实影响。相比之下，专注于临床结局（如ESLD）的研究更可取，因为它们可以包括典型的HIV/HCV合并感染患者。由于数据显示女性肝病进展比男性慢得多，因此HIV/HCV合并感染女性的ESLD风险因素和预测因素可能与男性不同，应单独检查。为了开始解决这些问题，本提案有三个具体目标：1）确定HIV/HCV共感染男性中ESLD的风险因素，2）推导并内部验证临床预测指数，以根据进展为ESLD的风险对HIV/HCV共感染男性进行分层，以及3）验证临床、实验室、妇女机构间艾滋病毒研究收集的数据和药房数据，以确定艾滋病毒/HCV合并感染ESLD的妇女。具体目标1和2将利用退伍军人老龄化队列研究的数据，这是一项多中心前瞻性队列研究，对八个退伍军人管理局医疗中心的艾滋病毒阳性和阴性退伍军人进行护理。具体目标3将利用来自妇女机构间艾滋病毒研究的三个地点的数据，这是一项对艾滋病毒阳性和阴性妇女的前瞻性队列研究。在完成这些目标后，PI将对HIV感染男性中HCV合并感染的自然史和风险因素的知识做出实质性贡献，并准备在未来对HIV感染女性中HCV合并感染的自然史知识做出类似贡献。