ALCOHOL EFFECTS ON LIVER DISEASE IN HCV AND HIV COINFECT

描述：（申请人摘要） 丙型肝炎（HCV）和人类免疫缺陷病毒（HIV）引起慢性 全球性的感染。因为它们有共同的胃肠外因素， 在艾滋病毒传播方面，超过三分之一的艾滋病毒感染者通常同时感染 在美国，有近40万人对这两种病毒都呈阳性 病毒合并感染的患者有更严重的肝病， 肝硬化的发病率比单纯HCV感染的患者高。虽然原因 因为这是不清楚的，这是可能的，共存的酒精中毒， 人口至少有部分责任。酒精可以进一步调节宿主 免疫抑制，并对宿主免疫防御产生特异性影响， 增加病毒复制和对HCV的突变压力。总目标 这项建议的目的是研究和澄清酒精对HCV的影响， 合并感染HIV的患者中的进行性肝病。的 具体目标是：1）我们将评估一组HCV/HIV阳性患者 并确定社会人口统计学，组织学和临床变量， 这些人受到过量饮酒的影响， 可能对进行性肝病很重要。2)然后我们将测序 并比较从这些患者中分离的HCV的重要基因组区域， 确定准种多样性对HCV病理学的意义。3)我们 将研究抗病毒治疗对组成和多样性的影响， HCV基因组区域，并确定其对患者预后的重要性， 对治疗的反应。我们的工作将阐明流行病学，自然史， 和酒精病理学的关系。它还将提供更多的 了解该人群中的进行性肝病， 未来的管理和抗病毒治疗。

DESCRIPTION: (Applicant's Abstract) Hepatitis C (HCV) and Human Immunodeficiency virus (HIV) cause chronic infections of worldwide importance. Because they share parenteral factors for transmission, over one third of patients with HIV are usually co-infected with HCV and nearly 400,000 individuals in the United States are positive for both viruses. Patients with co-infection have more aggressive liver disease and increased incidence of cirrhosis than patients with HCV only. While the reasons for this are unclear, it is possible that co-existent alcoholism in this population is at least partially responsible. Alcohol may further modulate host immune suppression and have specific effects on host immune defenses resulting in increased viral replication and mutational pressure on HCV. The overall goal of this proposal is to study and clarify the effects of alcohol on HCV and progressive liver disease in patients who are co-infected with HIV. The specific aims are: 1) We will evaluate a cohort of HCV/HIV positive patients and identify the sociodemographic, histological, and clinical variables of these individuals that are affected by excess alcohol consumption and most likely to be important for progressive liver disease. 2) We will then sequence and compare important genomic regions of HCV isolated from these patients and determine the significance of quasispecies diversity for HCV pathology. 3) We will study the effects of antiviral therapy on the composition and diversity of HCV genomic regions and determine their importance for patient prognosis and response to therapy. Our work will clarify the epidemiology, natural history, and pathology of alcohol in these patients. It will also provide an increased understanding of progressive liver disease in this population that will aid in future management and antiviral therapy.