CONTROLLED TRIAL OF CHLORAMBUCIL THERAPY IN PRIMARY BILIARY CIRRHOSIS

原发性胆汁性肝硬化是一种病因不明的疾病 以缓慢进行性肝内胆汁淤积为特征， 到非化脓性，可能是自身免疫性， 和较大的小叶间胆管。 因为某些其他的 自身免疫性疾病似乎对烷化剂 药物，苯丁酸氮芥治疗患者的对照试验 有症状的PBC进行了检查。 24例患者 纳入本试验：13例随机接受苯丁酸氮芥 治疗组（0.5-4.0 mg/天）和11例未接受治疗。 剂量 调整苯丁酸氮芥的剂量，以减少外周血 淋巴细胞计数减少50%，并保持多形核细胞 白细胞计数高于1000/c.mm.。在随访期间，2例患者 死亡：两者均为对照组。 平均血清胆红素水平降低 在治疗组中略有增加，但在 对照 到2年时，平均血清白蛋白增加 在治疗的患者中显著降低，但在对照组中降低。 是说 治疗组血清转氨酶水平显著降低， 患者比对照组。 平均血清免疫球蛋白（IgM和IgG） 水平从升高值降至正常值 所有苯丁酸氮芥治疗的患者中， 在控制。 一次和/或两次给药后肝活检组织病理学检查 结果显示炎症明显减少， 纤维化和疾病阶段的进展较少， 比对照组患者。 的潜在副作用 苯丁酸氮芥治疗包括两个绝经期的开始， 单纯疱疹或带状疱疹3例， 持续性白细胞减少症或血小板减少症患者， 停药。 这些发现有力地表明， 苯丁酸氮芥治疗可延缓PBC的进展， 寻找更安全（例如，非致癌）和更有效的 用于治疗这种疾病的免疫抑制方案是 可能会有回报。

Primary biliary cirrhosis (PBC) is a disease of unknown etiology characterized by slowly progressive intrahepatic cholestasis due to non-suppurative, presumably autoimmune, destruction of septal and the larger interlobular bile ducts. Because certain other autoimmune diseases appear to respond favorably to alkylating agents, a controlled trial of chlorambucil therapy for patients with symptomatic PBC has been conducted. Twenty-four patients were admitted to this trial: 13 were randomized to receive chlorambucil therapy (0.5-4.0 mg/day) and 11 to receive no treatment. The dose of chlorambucil was adjusted to reduce the peripheral blood lymphocyte count by 50% and maintain the polymorphonuclear leukocyte count above 1000 per c.mm. During follow-up, two patients died: both were controls. Mean serum bilirubin levels decreased slightly in the treated group but increased significantly in the controls. By 2 years the mean serum albumin had increased significantly in treated patients but decreased in controls. Mean serum transaminase levels became significantly less in treated patients than in controls. Mean serum immunoglobulin (IgM and IgG) levels decreased from elevated values to values within the normal range in all chlorambucil-treated patients, but remained elevated in controls. Liver biopsy histopathology after one and/or two years revealed significantly less inflammation, slightly less fibrosis and less progression of the stage of disease in the treated than in the control patients. Potential side effects of chlorambucil therapy included the onset of menopause in two patients, localized herpes simplex or zoster in 3 and, in 4 patients, persistent leukopenia or thrombocytopenia requiring discontinuation of the drug. These findings strongly suggest that chlorambucil therapy retards the progression of PBC, and that a search for safer (e.g. noncarcinogenic) and more effective immunosuppressive regimes for the treatment of this disease is likely to be rewarding.