PENTOXIFYLLINE FOR CIRRHOTIC PATIENTS WITH HEPATOPULMONARY SYNDROME

己酮可可碱治疗肝硬化肝肺综合征患者

• 批准号: 7380445
• 负责人: MICHAEL B FALLON
• 金额: $ 0.02万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7380445
• 关键词: PENTOXIFYLLINE; CIRRHOTIC; PATIENTS; HEPATOPULMONARY; SYNDROME

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chronic liver disease and its complications cause significant morbidity and mortality and rank among the top ten causes of death in the United States. One unique complication is the hepatopulmonary syndrome (HPS) which is found in 8-15% of patients with cirrhosis and results when intrapulmonary microvascular dilatation results in hypoxemia. There are no effective medical therapies for HPS. Liver transplantation is the sole treatment option, although peri-operative mortality appears higher in patients with HPS than in patients without HPS, particularly when severe. Despite the prevalence of HPS and the UNOS policy of increasing priority for transplantation once moderate hypoxemia due to HFS is present, fundamental questions and a lack of prospective data remain regarding epidemiology, natural history, pathogenesis, therapy, and the efficacy of transplantation. These questions and the unique nature of this disorder highlight the importance of developing a network of liver transplantation centers with specific experience and interest to study this syndrome. Experimental work in HPS models provides a rationale for exploring specific genetic polymorphisms as contributors to susceptibility and for defining whether pentoxifylline ameliorates gas exchange abnormalities. The broad goal of this project is to understand the epidemiology, natural history, and pathogenesis of HPS in order to maximize patient outcomes and develop effective therapies. To accomplish this goal, the following specific aims will be undertaken. In Aim 1, we will establish an alliance of academic centers with expertise in advanced liver disease, liver transplantation, and pulmonary vascular disease to study HPS by a) developing an organizational infrastructure, b) defining diagnostic criteria and c) standardizing evaluation and establishing clinical tissue and specimen acquisition. In Aim 2, we will use the alliance to investigate clinical outcomes, pathogenesis and therapy of HPS by a) initiating prospective evaluation, data and specimen collection and clinical follow up, b) defining if genetic polymorphisms in specific candidate genes are associated with susceptibility to HPS and c) designing and initiating an open label pilot trial of pentoxifylline in severe HPS. The data obtained from completion of these aims will be used to design and submit an RO-1 application by the HPS Investigative Group.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。慢性肝病及其并发症引起了显着的发病率和死亡率，并在美国的死亡原因中排名占。一种独特的并发症是肝肺综合征（HPS），在8-15％的肝硬化患者中发现，当肺内微血管扩张时会导致低氧血症。 HPS没有有效的医疗疗法。肝移植是唯一的治疗选择，尽管HPS患者的围手术期死亡率比没有HP的患者高，尤其是在严重时。尽管HPS的流行率和UNOS的政策是由于HFS引起的中度低氧血症而提高了移植优先级，但仍存在基本问题和缺乏有关流行病学，自然病史，发病机理，治疗和移植效率的预期数据。这些问题和这种疾病的独特性强调了开发具有特定经验和研究这种综合征的肝移植中心网络的重要性。 HPS模型中的实验工作为探索特定的遗传多态性作为对易感性的贡献和定义五氧化苯胺是否可以改善气体交换异常的理由。该项目的广泛目标是了解HPS的流行病学，自然史和发病机理，以最大程度地提高患者结局并开发有效的疗法。为了实现这一目标，将实现以下特定目标。在AIM 1中，我们将建立一个在晚期肝病，肝脏移植和肺血管疾病方面具有专业知识的学术中心联盟，以通过a）开发组织基础设施，b）定义诊断标准和c）标准化评估并确定临床组织和标本的恢复。 In Aim 2, we will use the alliance to investigate clinical outcomes, pathogenesis and therapy of HPS by a) initiating prospective evaluation, data and specimen collection and clinical follow up, b) defining if genetic polymorphisms in specific candidate genes are associated with susceptibility to HPS and c) designing and initiating an open label pilot trial of pentoxifylline in severe HPS.从完成这些目标获得的数据将用于设计和提交HPS调查小组的RO-1申请。