TRIALS OF THERAPIES FOR PRIMARY BILIARY CIRRHOSIS

摘要原发性胆汁性肝硬变是一种未知的自身免疫性疾病。 以慢性进行性肝内胆汁淤积为特征的病因 小肝内胆汁的非化脓性炎性破坏 风管。因为其他一些自身免疫性疾病似乎反应良好 对某些免疫抑制剂，选择免疫抑制剂的试验 正在对PBC患者进行药物治疗。在随机化的 百菌清治疗的对照试验，用该药治疗 随着血清胆红素升高率的降低， 升高的血清IgM水平正常化和改善 肝活检组织中的炎性细胞浸润。这些令人鼓舞的消息 这一发现促使人们寻找更安全、更有效的药物 致癌潜力低于氯氨丁苯的免疫抑制药物。 这种类型的一种很有前途的药物是甲氨蝶呤。10名患者患有 将有症状的PBC纳入一次低剂量(15 Mg)的开放试验 每周口服甲氨蝶呤。2例晚期(III-IV期)患者 4-5个月后病情消失。剩下的7人被跟踪了8年- 24个月。在这些患者中，甲氨蝶呤的治疗与 升高的血清免疫球蛋白M和碱性显著降低 磷酸酶和超过50%的疲劳和症状评分下降 瘙痒。血清ALT水平最初升高(4mo和8mo)。但 随后下降到比基线低10%。在4例患者中，谁有肝脏 在治疗前和治疗一年后进行活组织检查，提示甲氨蝶呤 启动两个剂量的甲氨蝶呤(7.5和 每周15毫克)，用于无症状和有症状的PBC患者。

Primary biliary cirrhosis (PBC) is an autoimmune disease of unknown etiology characterized by slowly progressive intrahepatic cholestasis due to non-suppurative inflammatory destruction of small intrahepatic bile ducts. Because some other autoimmune diseases appear to respond favorably to certain immunosuppressive agents, trials of selected immunosuppressive drugs are being undertaken in patients with PBC. In a randomized controlled trial of chlorambucil therapy, treatment with the drug was associated with a decrease in the rate of increase of serum bilirubin, normalization of elevated serum IgM levels and an improvement in inflammatory cell infiltration in liver biopsies. These encouraging findings have prompted a search for safer and more effective immunosuppressive drugs with less carcinogenic potential than chlorambucil. One promising drug of this type is methotrexate. Ten patients with symptomatic PBC were admitted to an open trial of low-dose (15 mg) once weekly oral methotrexate. Two patients with advanced (stage III-IV) disease dropped out after 4-5 months. The remaining 7 were followed for 8- 24 months. Methotrexate therapy in these patients was associated with significant decreases in elevated serum levels of IgM and alkaline phosphatase and a more than 50% decrease in symptom scores for fatigue and pruritus. Serum ALT levels initially increased (4 and 8 mo.) but subsequently fell to 10% below baseline. In 4 patients, who had liver biopsies before and after one year of treatment, methotrexate was prompted the initiation of a randomized trial of two doses of methotrexate (7.5 and 15 mg/week) for asymptomatic as well as symptomatic patients with PBC.