Clinical Core

慢性丙型肝炎病毒感染的自然病史差异很大，回顾研究发现，进展缓慢的患者需要40年才能发展为肝硬变，而进展迅速的患者可能在短短10-20年内发展为晚期纤维化。与疾病进展相关的潜在病理生理机制尚不清楚，并代表了这个丙型肝炎中心的中心焦点。我们将研究疾病进展速度不同的患者队列。丙型肝炎病毒疾病进展临床中心将提供肝组织、标本、临床专业知识、生物统计学和病理学核心，以与 丙型肝炎病毒中心提案中的基本调查人员。该临床中心将利用现有的队列，并开发新的疾病进展缓慢或快速的患者队列，以研究与肝纤维化进展相关的潜在免疫学、病毒学和代谢因素。具体来说，我们将开发：1)丙型肝炎患者疾病进展和纤维化机制的临床研究基础 2)对4组不同的纤维化进展速度不同的患者进行评估： A)单纯接受治疗的丙型肝炎患者代表以进展缓慢为主的对照组B)丙型肝炎和血吸虫病患者迅速发展为肝硬变 C)艾滋病毒/丙型肝炎患者；其中一部分患者免疫功能低下，CD4细胞计数低，病情进展更快；D)肝移植后丙型肝炎复发的患者 这些研究可能有助于确定纤维化进展的机制，并导致合理使用资源来识别和治疗疾病进展风险较高的患者。

The natural history of chronic HCV infection is very variable and retrospective studies have identified both slow progressors who take 40 years to develop cirrhosis and rapid progressors who may develop advanced fibrosis in as little as 10 - 20 years. The underlying pathophysiological mechanisms associated with disease progression are poorly understood and represent the central focus of this HCV Center. We will study cohorts of patients with variable rates of disease progression. The Clinical Center for HCV disease progression will provide liver tissues, specimens, clinical expertise, biostatistics and a pathology core to interact with the basic Investigators in this HCV Center proposal. The clinical center will utilize both existing cohorts and develop novel cohorts of patients with either slow or fast disease progression to study the underlying immunological, virological and metabolic factors associated with progression of liver fibrosis. In particular we will develop: 1) the Infrastructure for clinical investigation into mechanisms of disease progression and fibrosis in patients with HCV 2) Evaluation of 4 distinct cohorts of patients who have variable rates of fibrosis progression: A) Patients with HCV naive to treatment representing a control group of predominantly slow progressors B) Patients with HCV and Schistosomiasis who rapidly develop cirrhosis C) Patients with HIV/HCV; a subset of whom are immunocompromised with low CD4 counts and may progress more rapidly D) Patients post liver transplant who have recurrent HCV These studies may help identify the mechanism of fibrosis progression and lead to rational use of reources to identify and treat patients at higher risk of disease progression.