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)导致慢性 具有世界重要性的传染病。因为他们有共同的肠外因子 传播，超过三分之一的艾滋病毒患者通常合并感染 丙型肝炎病毒和美国近40万人两者均呈阳性 病毒。合并感染的患者有更具侵袭性的肝病和 与单纯丙型肝炎患者相比，肝硬变的发生率更高。虽然原因是 对于这一点尚不清楚，有可能是酒精中毒并存于此 人口至少要对此负部分责任。酒精可进一步调节宿主 免疫抑制，并对宿主免疫防御产生特定影响 在病毒复制增加和丙型肝炎病毒变异压力方面。总目标 这项建议的目的是研究和澄清酒精对丙型肝炎病毒和 合并感染艾滋病毒的患者中的进行性肝病。这个 具体目标是：1)我们将评估一组丙型肝炎病毒/艾滋病毒阳性患者 并确定其社会人口学、组织学和临床变量 这些受过量饮酒影响的人和大多数 可能对进行性肝病很重要。2)然后我们将排序 并将从这些患者中分离的丙型肝炎病毒的重要基因组区域与 确定准种多样性对丙型肝炎病毒病理的意义。3)我们 将研究抗病毒治疗对细菌组成和多样性的影响 确定其对患者预后和预后的重要性 对治疗的反应。我们的工作将阐明流行病学，自然病史， 以及酒精在这些患者中的病理变化。它还将提供更多的 对该人群中进行性肝病的了解将有助于 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.