A PROSPECTIVE TRIAL OF COLCHICINE FOR PRIMARY BILIARY-CIRRHOSIS
A PROSPECTIVE TRIAL OF COLCHICINE FOR PRIMARY BILIARY-CIRRHOSIS
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DOI：
10.1056/nejm198612043152304
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发表时间：
1986-12-04
影响因子：
158.5
通讯作者：
EAGEN, KA
中科院分区：
文献类型：
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作者：
KAPLAN, MM;ALLING, DW;EAGEN, KA
我们将60例原发性胆汁性肝硬化患者纳入一项双盲随机对照试验，以确定秋水仙碱是否有效。30例患者患有早期疾病（1期和2期），30例患有晚期疾病（3期和4期）。15名早期疾病患者和15名晚期疾病患者接受秋水仙碱（0.6 mg，每日两次），其余患者接受安慰剂。大约每两个月对患者进行一次研究;那些在两年后仍处于盲期的患者进行重复肝活检，然后接受开放标签的秋水仙碱（0.6 mg，每日两次）。除少数例外情况外，早期疾病患者的结果与晚期疾病患者的结果相似;因此，在主要分析中合并了所有阶段患者的数据。在两年的研究期间，与安慰剂治疗的患者相比，秋水仙碱治疗的患者的血清白蛋白、血清胆红素、碱性磷酸酶、胆固醇和转氨酶水平有所改善。然而，症状或体格检查结果的严重程度没有改善;此外，两个治疗组的活检组织学变化没有显著差异。在进入后四年，肝脏疾病的累积死亡率在给予秋水仙碱的患者中为21%，在给予安慰剂的患者中为47%（P = 0.05）。秋水仙碱的唯一副作用是腹泻，在三名患者中观察到。一些肝病标志物的一致和显著改善以及肝病死亡率的明显降低表明秋水仙碱可能为原发性胆汁性肝硬化患者提供一些长期的临床获益。然而，秋水仙碱未能减少肝脏炎症和纤维化，因此不确定该药物对这种疾病的长期结局的影响。
We entered 60 patients with primary biliary cirrhosis in a double-blind randomized controlled trial to determine whether colchicine is therapeutically effective. Thirty patients had early disease (stages 1 and 2), and 30 had advanced disease (Stages 3 and 4). Fifteen patients with early disease and 15 with advanced disease received colchicine (0.6 mg twice daily), and the remainder received placebo. Patients were studied about every two months; those remaining in the blind phase at two years underwent repeat liver biopsy and were then placed on open-label colchicine (0.6 mg twice daily). With a few exceptions, the results in patients with early disease were similar to those in patients with advanced disease; hence, data on patients in all stages were combined in the main analysis. During the two-year study period the colchicine-treated patients, as compared with the placebo-treated patients, had improvement in levels of serum albumin, serum bilirubin, alkaline phosphatase, cholesterol, and aminotransferase. However, there was no such improvement in the severity of symptoms or physical findings; moreover, there was no significant difference in the histologic changes noted at their biopsy in the two treatment groups. At four years after entry, the cumulative mortality from liver diseases was 21 percent in patient given colchicine and 47 percent in those given placebo (P = 0.05). The only side effect of colchicine was diarrhea, noted in three patients. The consistent and significant improvement in a number of marks of liver disease and the apparent decreased mortality from liver disease suggest that colchicine may provide some long-term clinical benefit in patients with primary biliary cirrhosis. However, the failure of colchicine to reduce hepatic inflammation and fibrosis leaves uncertain the effect of the drug on the long-term outcome of this disease.