TRIALS OF THERAPIES FOR PRIMARY BILIARY CIRRHOSIS

原发性胆汁性肝硬化的治疗试验

• 批准号: 6105841
• 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/6105841
• 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 affects small intrahepatic bile ducts. It affects approximate 1 in 2,000 women above the age of 50 and it is one of the 3 or 4 major reasons for liver transplantation in the US. Several trials have been conducted to study the effect of immunosuppressants in PBC including methotrexate (MTX). A randomized trial comparing the effects of 7.5 vs 15 mg per week of oral MTX was started in 1991 and will be completed in 1998. 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 falls of IgM levels to normal. Symptoms improved in 43 per cent of patients and liver histology in 46 per cent. The higher dose was associated with greater improvements in liver histology but the lower dose was effective in a similar percentage of patients. Prolonged therapy was able to maintain improvements in the percentage of patients who had a clinical or histological improvement in disease. These results indicate that prolonged therapy with adjusted doses of MTX may be effective in ameliorating symptoms and liver pathology in PBC.

原发性胆道肝硬化（PBC）是进行性肝 被认为具有自身免疫性的疾病。它的病因是 未知。它的特征是进行性肝内胆汁淤积 由于持续的非支持破坏性胆管炎的结果 影响小肝内胆管。它影响大约1 2,000名50岁以上的妇女是3或4大专业之一 在美国进行肝移植的原因。几次试验 进行研究以研究免疫抑制剂在PBC中的影响 包括甲氨蝶呤（MTX）。比较的随机试验 1991年开始，7.5 vs每周口服MTX的效果 并将在1998年完成。28例患者被随机分配给 接受两种剂量之一，并根据 存在或不存在症状。治疗导致减少 血清碱性磷酸酶和氨基转移酶的水平和下降 IgM水平正常。症状改善了43％ 患者和肝组织学占46％。较高的剂量是 与肝组织学的改善相关，但 较低剂量在类似百分比的患者中有效。 长时间的治疗能够维持 患有临床或组织学的患者百分比 疾病的改善。这些结果表明延长 用调整剂量的MTX治疗可能有效 PBC中的改善症状和肝脏病理学。