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。 以缓慢进行性肝内胆汁淤积为特征的病因学 小肝内非化脓性炎性破坏 胆管。因为其他一些自身免疫性疾病似乎对 对某些免疫抑制剂有利，选定的试验 PBC患者正在接受免疫抑制药物的治疗。一 这种类型很有前景的药物是甲氨蝶呤。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8个已经被跟踪 长达36个月。这些患者的甲氨蝶呤治疗是 与升高的血清IgM水平显著下降有关 和碱性磷酸酶，症状评分下降超过50% 用于治疗疲劳和瘙痒。血清ALT水平最初升高(在4和 8个月。)但平均数随后下降到比基线低10%。在8年内 患者在治疗前和治疗一年后都进行了肝脏活检， 甲氨蝶呤与肝脏的显著减少有关 炎症反应，但纤维化无明显变化。第III期患者 疾病在治疗的第二年和甲氨蝶呤进展 其中3名患者停药。两种剂量的随机试验 甲氨蝶呤(7.5和15毫克/周)治疗无症状和 已经启动了有症状的PBC患者。已经有25名患者被 承认参加了这场审判。

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. 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 8 have been followed for up to 36 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 (at 4 and 8 mo.) but the mean subsequently fell to 10% below baseline. In 8 patients, who had liver biopsies before and after one year of treatment, methotrexate was associated with a substantial decrease in hepatic inflammation but no obvious change in fibrosis. Patients with Stage III disease progressed during the second year of treatment and methotrexate was discontinued in 3 of these patients. A randomized trial of two doses of methotrexate (7.5 and 15 mg/week) for asymptomatic as well as symptomatic patients with PBC has been initiated. 25 patients have been admitted to this trial.