Hoofnagle J H, Davis G L, Schafer D F, Peters M, Avigan M I, Pappas S C, Hanson R G, Minuk G Y, Dusheiko G M, Campbell G
Gastroenterology. 1986 Dec;91(6):1327-34. doi: 10.1016/0016-5085(86)90183-6.
Twenty-four patients with primary biliary cirrhosis were entered into a prospective, randomized trial of chlorambucil therapy. Thirteen patients received chlorambucil (0.5-4 mg/day) and 11 patients received no therapy; all have been followed for 2-6 yr (mean, 4.1 yr). Two control but no treated patients died. Average serum bilirubin, serum aspartate aminotransferase activities, and albumin levels improved or remained unchanged in treated patients but worsened in controls. Serum alkaline phosphatase levels did not change in either group. Immunoglobulin M levels decreased and became normal in all treated patients but in only 3 control patients. Liver biopsy histology revealed an improvement in inflammatory cell infiltrate in treated patients in comparison with controls, but no significant change in degree of fibrosis or the histologic stage of disease. Side effects of therapy included bone marrow suppression necessitating discontinuation of the drug in 4 patients. These findings indicate that chlorambucil therapy may retard the progression of primary biliary cirrhosis. Whether such therapy will ultimately decrease morbidity and improve survival in this disease can only be demonstrated by large-scale, placebo-controlled trials.
24例原发性胆汁性肝硬化患者进入苯丁酸氮芥治疗的前瞻性随机试验。13例患者接受苯丁酸氮芥治疗（0.5 - 4毫克/天），11例患者未接受治疗；所有患者均随访2 - 6年（平均4.1年）。2例未接受治疗的对照患者死亡。治疗组患者的平均血清胆红素、血清天冬氨酸转氨酶活性和白蛋白水平有所改善或保持不变，而对照组患者则恶化。两组患者的血清碱性磷酸酶水平均未发生变化。所有接受治疗的患者免疫球蛋白M水平均下降并恢复正常，而对照组仅有3例患者如此。肝活检组织学显示，与对照组相比，治疗组患者的炎性细胞浸润有所改善，但纤维化程度或疾病组织学分期无显著变化。治疗的副作用包括骨髓抑制，4例患者因此需要停药。这些发现表明，苯丁酸氮芥治疗可能会延缓原发性胆汁性肝硬化的进展。这种治疗是否最终会降低该病的发病率并提高生存率，只能通过大规模、安慰剂对照试验来证明。
