TRIALS OF THERAPIES FOR PRIMARY BILIARY CIRRHOSIS

原发性胆汁性肝硬化（PBC）是一种进行性肝病，被认为是自身免疫性的。其病因不明。其特征是进行性肝内胆汁淤积，这是由于持续的非化脓性破坏性胆管炎影响小的肝内胆管。它影响大约1/2，000 50岁以上的女性，是美国肝移植的3或4个主要原因之一。已经进行了几项试验来研究免疫抑制剂在PBC中的作用，包括甲氨蝶呤（MTX）。1991年开始了一项随机试验，比较每周口服MTX 7.5 mg与15 mg的效果，并于1998年完成治疗。28例患者随机接受两种剂量之一，并根据症状的存在或不存在进行分层。治疗导致血清碱性磷酸酶和转氨酶水平降低，IgM水平福尔斯降至正常。43%的患者症状得到改善，46%的患者肝组织学得到改善。高剂量与肝组织学的更大改善相关，但低剂量在相似比例的患者中有效。延长治疗能够维持疾病临床或组织学改善的患者百分比的改善。这些结果表明，MTX的剂量调整延长治疗可能是有效的，在PBC的症状和肝脏病理改善。目前，所有患者都在接受随访，并在停止甲氨蝶呤三年后进行重新评估，以评估临床、生化和组织学反应的持久性。- 胆汁淤积/自身免疫性疾病/免疫抑制剂-人类受试者

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 therapy was 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. At present all patients are being followed and undergo reassessment three years after stopping methotrexate to assess the durability of clinical, biochemical and histological responses. - Cholestasis/Autoimmune Disease/Immunosuppressants - Human Subjects