HIGH DOSE UDCA FOR PRIMARY SCLEROSING CHOLANGITIS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究旨在确定高剂量熊去氧胆酸（UDCA）治疗原发性硬化性胆管炎（PSC）的安全性和有效性。 PSC是一种原因不明的慢性肝病。 它的特点是炎症和破坏肝（肝）胆管。 这种疾病是缓慢进行的，通常会导致肝硬化，高血压和肝功能衰竭超过10-15年的时间。 PSC是美国成人最常见的肝脏疾病之一，也是肝移植的重要指征。 PSC的原因不明。 在至少70%的病例中，PSC与炎症性肠病和溃疡性结肠炎有关。 目前还没有关于PSC有效药物治疗的报告。 肝脏疾病的传统治疗方法尚未被证明在PSC的治疗中有效。 毒性胆汁酸的蓄积可能是PSC损伤的重要机制。 因此，使用UDCA治疗PSC的依据包括其发挥免疫修饰作用并用毒性较低的胆汁酸（UDCA）替代胆汁酸的证据。 在PSC患者的初步研究中，UDCA在24个月的治疗中改善了肝酶。 另一项小型试验在接受UDCA治疗的患者中产生了组织改善。 一项更大规模的随机研究显示，治疗或死亡终点无显著变化，但UDCA剂量较小。 本研究的目的是确定较高剂量UDCA治疗PSC是否有效。 将对患者进行至少4年的随访研究，以确定高剂量UDCA的长期影响。 受试者访视将在GCRC进行。 将对所有受试者进行医学和体格检查、血液测量和组织样本采集。 此外，还可以进行其他常规诊断测试。 对于任何额外的手术，患者将被要求签署单独的知情同意书。 本研究期间进行的所有检查将根据PSC患者治疗的标准治疗进行。 数据将用于确定高剂量UDCA对PSC患者的有效性。

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. The purpose of the research study is to determine the safety and effectiveness of high doses of Ursodiol, a ursodeoxycholic acid (UDCA), in the treatment of primary sclerosing cholangitis (PSC). PSC is a chronic liver disease of unknown cause. It is characterized by inflammations and destruction of the hepatic (liver) bile ducts. The disease is slowly progressive and usually leads to cirrhosis, hypertension and liver failure over a 10-15 year period. PSC is one of the most common liver diseases and an important indication for liver transplantation in US adults. The cause of PSC is unknown. In at least 70% of the cases, PSC is associated with inflammatory bowel disease and ulcerative colitis. There are no reports of effective medical therapy for PSC at this time. Traditional treatments for liver disease have not been proven effective in the treatment of PSC. The accumulation of toxic bile acids may be an important mechanism of injury in PSC. Therefore, the rationale for using UDCA in the treatment of PSC includes evidence that it plays an immune modifiying role and replaces the bile acid with a less toxic bile acid (UDCA). In a pilot study of patients with PSC, UDCA improved liver enzymes over 24 months of treatment. Another small trial produced tissue improvements in those treated with UDCA. A larger randomized study showed no significant changes in treatment or death endpoints, however, the dose of UDCA was small. The purpose of this study is to determine if treatment with higher doses of UDCA is effective in the treatment of PSC. Patients will be studies for a minimum of four years of follow-up to determine the long term effects of high doses of UDCA. A subjects visits will be held in the GCRC. Medical and physical examinations, blood measurements, and tissue sample collection will be done for all subjects. In addition, other routine diagnostic tests may be performed. Patients will be required to sign separate consent forms for any additional procedures. All tests done during this study will be done according to the standard of care for treatment of patients with PSC. Data will be used to determine the effectiveness of UDCA in high doses for patients with PSC.