CONTROLLED TRIAL OF CHLORAMBUCIL THERAPY IN PRIMARY BILIARY CIRRHOSIS

苯丁酸氮芥治疗原发性胆汁性肝硬化的对照试验

• 批准号: 3941106
• 负责人: E A JONES
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3941106
• 关键词: adult human (21+); alkylating agents; autoimmune disorder; biliary tract disorder chemotherapy; bilirubin; biopsy; blood cell count; chlorambucil; copper; corticosteroids; dosage; drug adverse effect; histopathology; human subject; human therapy evaluation; immunoglobulin G; immunoglobulin M; immunosuppressive; liver cirrhosis; longitudinal human study; orphan disease /drug; serology /serodiagnosis

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.

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 入选本试验：13例随机接受 苯丁酸氮芥治疗组（0.5-4.0 mg/d）和对照组（11例）（无 治疗组。 调整了氯丁酸氮芥的剂量， 外周血淋巴细胞计数减少50%， 保持多形性白细胞计数高于1000， 所有患者均随访2-6年（平均= 4.1 年）。 在随访期间，两名患者死亡：均为对照组。 治疗组的平均血清胆红素水平略有下降， 但在对照组中显著增加。 2年后， 治疗组的平均血清白蛋白显著改善， 患者，但在控制下降。 平均血清转氨酶 治疗患者的水平显著低于对照组。 平均血清免疫球蛋白（IgM和IgG）水平从 所有患者的数值升高至正常范围内 苯丁酸氮芥治疗的患者，但没有明显改变， 对照 1年和/或2年后的肝活检组织病理学 显示炎症明显减少，纤维化轻微减少， 治疗组的疾病阶段进展小于对照组， 对照患者。 苯丁酸氮芥治疗的潜在副作用 包括两名患者的绝经期开始，局部疱疹， 3例单纯性或带状疱疹，4例持续性白细胞减少， 需要停药的血小板减少症。 这些 研究结果强烈表明，苯丁酸氮芥治疗延缓了 建设和平委员会的进展，并为寻求 更安全（例如，无致癌性）和更有效 用于治疗这种疾病的免疫抑制方案。