URSODIOL-METHOTREXATE FOR PRIMARY BILIARY CIRRHOSIS

这项随机、双盲临床试验的主要目的是 确定原发性胆道疾病患者的治疗方案 乌索二醇(熊去氧胆酸-UDCA)联合治疗肝硬变(PBC) 甲氨蝶呤(MTX)比单独使用UDCA更有效。 慢性胆汁淤积性肝病是一种慢性淤胆性肝病，主要发生在女性。 小叶间胆管和间隔胆管经历炎症和 毁灭。一旦开始，这种疾病就会持续并在 不同的利率。无论是启动机制还是永久机制都不是 很好理解。目前发病机制的概念包括(1) 胆管的破坏是持续的，可能是由 自身免疫机制；(2)体内聚集的疏水性胆汁酸 血清和肝脏引起功能性和细胞毒性肝损伤； 炎症部位释放的细胞因子和淋巴因子可能 会导致细胞损伤和纤维化。相当多的证据 表明口服UDCA可以改善肝脏检查， 在瘙痒症和肝脏组织学上。在意见上存在分歧 至于发展为肝病的并发症，肝脏 移植或非移植存活会受到影响。UDCA a 相对无毒的胆汁酸，当口服时，改变 胆酸池的组成与UDCA的富集性 对内源性胆汁的细胞毒性作用有保护作用 由于胆管破坏而积聚的酸。MTX是 被证明可以改善肝脏检查、症状和肝组织学 少数伴有PBC的肝硬变前期患者。作用机制 未知，但被认为与抗炎免疫抑制有关 甲氨蝶呤的影响。目前的试验探索了MTX是否改善了 UDCA治疗PBC的疗效观察PBC患者的血清 胆红素低于3mg%，至少已服用UDCA 6个月，并且满足一系列纳入和排除标准 根据肝组织学分期分为2组 (路德维希分类)，即早期(阶段I或阶段II)和晚期(阶段 III或IV)。然后他们被随机接受甲氨蝶呤或 它的安慰剂作为第二种药物，同时继续接受UDCA。这个 两种治疗手段的相对价值通过比较它们的 对症状、实验室测试结果、发展的影响 肝病并发症、肝、肝组织学改变 移植，以及无移植生存。每辆车的安全 治疗方案也在确定中。

The major thrust of this randomized, double-blinded clinical trial is to determine whether treatment of patients with Primary Biliary Cirrhosis (PBC) with Ursodiol (Ursodeoxycholic Acid-UDCA) plus methotrexate (MTX) is more effective than treatment with UDCA alone. PBC is a chronic cholestatic liver disease, predominantly of women, in which interlobular and septal bile ducts undergo inflammation and destruction. Once initiated, the disease persists and progresses at varying rates. Neither the initiating nor perpetuating mechanisms are well understood. Current concepts of pathogenesis include (1) destruction of bile ducts is maintained and perhaps initiated by autoimmune mechanisms; (2) hydrophobic bile acids which accumulate in serum and liver cause functional and cytotoxic liver injury; (3) cytokines and lymphokines released at sites of inflammation may contribute to cell damage and fibrosis. A considerable body of evidence indicates that UDCA when fed orally leads to improvement in liver tests, in pruritus and in liver histology. There exist differences in opinion as to whether development of complications of liver disease, liver transplantation or transplant-free survival is affected. UDCA a relatively non-toxic bile acid, when administered orally, alters the composition of the bile acid pool in factor of its enrichment with UDCA and appears to protect against the cytotoxic effects of endogenous bile acids that accumulate as a result of bile duct destruction. MTX is being shown to improve liver tests, symptoms and liver histology in a small number of precirrhotic patients with PBC. The mechanism of action is unknown but felt to be related to antiinflammatory-immunosuppressive effects of MTX. The current trial explores whether MTX improves the therapeutic effects of UDCA in PBC. Patients with PBC whose serum bilirubin is less than 3 mg percent, who have been on UDCA for at least 6 months, and who satisfy a series of inclusion and exclusion criteria are stratified into 2 groups on the basis of liver histologic stage (Ludwig classification), i.e. early (Stages I or II) versus late (Stages III or IV). They are then randomized to receive either methotrexate or its placebo as a second drug while continuing to receive UDCA. The relative value of the two treatment arms is assessed by comparing their effects on symptoms, results of laboratory tests, development of complications of liver disease, histologic changes in liver, liver transplantation, and on transplant-free survival. The safety of each therapeutic regimen is also being determined.