TRIALS OF THERAPIES FOR PRIMARY BILIARY CIRRHOSIS

原发性胆汁性肝硬化的治疗试验

• 批准号: 2573670
• 负责人: JAY H. HOOFNAGLE
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2573670
• 关键词: alkaline phosphatase; biliary tract disorder chemotherapy; clinical research; dosage; histology; human subject; human therapy evaluation; immunosuppressive; methotrexate; primary biliary cirrhosis; transaminases

Primary biliary cirrhosis (PBC) is a progressive liver disease believed to be of autoimmune nature. Its etiology is unknown. It is characterized by progressive intrahepatic cholestasis as a result of ongoing non-suppurative destructive cholangitis that affecting small intrahepatic bile ducts. It affects approximate 1 in 2000 women above the age of 50 and it is one of the 3 or 4 major reasons for liver transplantation in the U.S. Several trials have been conducted to study the effect of immunosuppressants in PBC including methotrexate (MTX). A randomized trial conparing the effects of 7.5 vs 15 mg per week of oral MTX was started in 1991 and completed in early 1995. 28 patients were randomized to receive one of the two doses and stratified according to the presence or absence of symptoms. Therapy led to decreases in serum alkaline phosphatase and aminotransferase levels and fall to IgM levels to normal. Symptoms improved in 43% of patients and liver histology in 46%. The higher dose was associated with greater improvements in liver histology but the lower dose was effective in a similar percentage of patients. These results indicate that prolonged therapy with adjusted doses of MTX may be effective in ameliorating symptoms and liver pathology in PBC.

原发性胆汁肝硬化（PBC）是一种进行性肝病 被认为是自身免疫性的。 它的病因是未知的。 这是 由于 持续的非支持破坏性胆管炎，影响小 肝内胆管。 它影响了2000年女性的大约1个 50岁，是肝脏的3或4个主要原因之一 美国的移植已进行了几项试验 研究包括甲氨蝶呤的PBC中免疫抑制剂的影响 （MTX）。 一项随机试验，连接7.5 vs 15 mg的效果 口服MTX的一周成立于1991年，于1995年初完成。28 患者被随机接受两种剂量之一，并且 根据存在或不存在症状进行分层。 治疗 导致血清碱性磷酸酶和氨基转移酶的减少 水平并跌至IgM水平正常。 43％的症状改善 患者和肝组织学分别为46％。 较高的剂量是相关的 肝组织学有所改善，但较低的剂量是 在类似百分比的患者中有效。 这些结果表明 经过调整剂量的MTX长期治疗可能有效 PBC中的改善症状和肝脏病理学。