CONTROLLED TRIAL OF CHLORAMBUCIL THERAPY IN PRIMARY BILIARY CIRRHOSIS

摘要原发性胆汁性肝硬变是一种病因不明的疾病。 以慢性进行性肝内胆汁淤积为特征 到非化脓性的，可能是自身免疫性的隔膜破坏 和较大的小叶间胆管。因为某些其他人 自身免疫性疾病似乎对烷化反应有利 氯氨丁苯治疗药物的对照试验 对有症状的患者进行了PBC。24名患者 被允许参加这项试验：13人被随机接受 氯苯丁尼(0.5-4.0 mg/d)和对照组(11例)。 治疗)组。氯氨丁苯的剂量调整为 将外周血淋巴细胞计数降低50%， 将多形核白细胞计数维持在1000个以上 C.嗯。所有患者均随访2-6年，平均为4.1 年)。在随访期间，两名患者死亡：均为对照组。 平均血清胆红素水平在治疗后略有下降 但在对照组中显著升高。在2岁的时候 平均血清白蛋白在治疗后显著改善 而对照组则有所下降。平均血清转氨酶 治疗组患者的血药浓度明显低于对照组。 意味着血清免疫球蛋白(IgM和Ig G)水平从 将值提升到正常范围内的值 接受氯苯丁腈治疗的患者，但在 控制。一年和/或两年后的肝活检组织病理学 显示炎症明显减轻，纤维化轻微减轻， 在接受治疗的患者中，疾病阶段的进展比在 控制病人。氯氨丁苯治疗的潜在副作用 包括开始绝经的两名患者，局限性疱疹 3例为单纯性或带状疱疹，4例为持续性白细胞减少或 需要停药的血小板减少症。这些 研究结果有力地表明，氯苯丁腈疗法延缓了 PBC的进展，它们提供了寻找 更安全(例如，非致癌)和更有效 治疗这种疾病的免疫抑制疗法。

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 the control (no treatment) group. The dose of chlroambucil was adjusted to reduce the peripheral blood lymphocyte count by 50% and maintain the poly-morphonuclear leukocyte count above 1000 per c.mm. All patients have been followed for 2-6 years (mean = 4.1 years). 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. At 2 years the mean serum albumin was significantly improved in treated patients but was decreased in controls. Mean serum transaminase levels were significantly less in treated patients than in controls. Means serum immunoglobulin (IgM and IgG) levels decreased from elevated values to values within the normal range in all chlorambucil-treated patients, but did not change appreciably 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 they provide an impetus to search for safer (e.g. noncarcinogenic) and more effective immunosuppressive regimes for the treatment of this disease.