TRIALS OF THERAPIES FOR PRIMARY BILIARY CIRRHOSIS

原发性胆汁性肝硬变(PBC)是一种进行性肝病，被认为是自身免疫性的。其病因尚不清楚。它的特点是由于持续的非化脓性破坏性胆管炎影响到小的肝内胆管而导致进行性肝内胆汁淤积。它影响到大约每2000名50岁以上的女性中就有一名，这是美国肝脏移植的3到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7.5毫克和15毫克口服甲氨蝶呤的疗效，治疗将于1998年完成。28名患者随机接受两种剂量中的一种，并根据有无症状进行分层。治疗后血清碱性磷酸酶和转氨酶水平下降，IgM水平降至正常。43%的患者症状有所改善，46%的患者肝脏组织学有所改善。较高剂量与肝脏组织学改善程度较大相关，但较低剂量对相似比例的患者有效。长期治疗能够保持患者在临床或组织学上有改善的百分比。这些结果表明，长期服用调整剂量的MTX可能对改善PBC的症状和肝脏病理是有效的。目前正在对所有患者进行跟踪，并在停用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。

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.