TRIALS OF THERAPIES FOR PRIMARY BILIARY CIRRHOSIS

摘要原发性胆汁性肝硬变是一种进行性肝病。 据信是自身免疫性的。其病因尚不清楚。它是 以进行性肝内胆汁淤积为特征的 持续的非化脓性破坏性胆管炎，影响小 肝内胆管。大约每2000名以上女性中就有1人患有此病。 50岁，是导致肝病的3到4个主要原因之一 移植在美国已经进行了几次试验，以 包括甲氨蝶呤在内的免疫抑制剂在PBC中的作用 (MTX)。一项随机试验，比较7.5毫克和15毫克每克的疗效 口服甲氨蝶呤周始于1991年，1995年初完成。28 患者随机接受两种剂量中的一种， 根据症状的存在或不存在而分层。治疗法 导致血清碱性磷酸酶和转氨酶下降 并降至正常的免疫球蛋白M水平。43%的患者症状有所改善 患者和肝组织学检查占46%。较高的剂量与 肝脏组织学有较大改善，但剂量较低 对类似比例的患者有效。这些结果表明 用调整剂量的MTX延长治疗时间可能对 改善PBC的症状和肝脏病理。

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.