A MULTICENTER, CONTROLLED TRIAL OF URSODIOL FOR THE TREATMENT OF PRIMARY BILIARY-CIRRHOSIS
A MULTICENTER, CONTROLLED TRIAL OF URSODIOL FOR THE TREATMENT OF PRIMARY BILIARY-CIRRHOSIS
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DOI：
10.1056/nejm199105303242204
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发表时间：
1991-05-30
影响因子：
158.5
通讯作者：
POUPON, R
中科院分区：
文献类型：
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作者：
POUPON, RE;BALKAU, B;POUPON, R
背景。在原发性胆汁性肝硬化中，肝脏病变可能至少部分是由潜在毒性内源性胆汁酸在细胞内积聚引起的。初步研究表明，熊二醇（也称为熊去氧胆酸）是一种无肝毒性的亲水性胆汁酸，可改善原发性胆汁性肝硬化患者的病情。我们进行了一项为期两年的多中心双盲试验，比较熊二醇与安慰剂的疗效。经活检证实的原发性胆汁性肝硬化患者被随机分配接受熊二醇（每天每公斤体重13至15毫克）（n = 73）或安慰剂（n = 73）。治疗失败的定义为胆红素水平翻倍至每升70 μ mol以上或出现严重并发症（腹水或静脉曲张出血）或不良反应。乌索二醇组治疗失败6例，安慰剂组治疗失败13例（Cox回归模型P < 0.01）。每组均有1例患者因轻微不良反应退出治疗。治疗2年后，只有熊二醇组出现临床显性疾病的比例下降（P < 0.02）。接受熊二醇治疗的患者血清胆红素、碱性磷酸酶、丙氨酸转氨酶、天冬氨酸转氨酶、γ -谷氨酰转移酶、胆固醇和IgM水平均有显著改善（均P < 0.001）；抗线粒体抗体滴度（P < 0.01）；Mayo风险评分（P < 0.001）。对95例肝活检标本的随访分析显示，除肝纤维化外，乌索酚组的平均组织学评分和所有特征性组织学特征均有显著改善（P < 0.002）。熊二醇是一种安全有效的治疗原发性胆汁性肝硬化的药物。
Background. In primary biliary cirrhosis the hepatic lesions may result, at least in part, from the intracellular accumulation of potentially toxic endogenous bile acids. Preliminary work suggests that the administration of ursodiol (also called ursodeoxycholic acid), a hydrophilic bile acid without hepatotoxicity, leads to improvement in the condition of patients with primary biliary cirrhosis.Methods. We conducted a two-year, multicenter, double-blind trial to compare the efficacy of ursodiol with that of placebo. Patients with biopsy-proved primary biliary cirrhosis were randomly assigned to receive either ursodiol (13 to 15 mg per kilogram of body weight per day) (n = 73) or placebo (n = 73). Treatment failure was defined as a doubling of bilirubin levels to more than 70-mu-mol per liter or the occurrence of a severe complication (ascites or variceal bleeding) or an adverse reaction.Results. Treatment failed in 6 patients in the ursodiol group, as compared with 13 in the placebo group (P < 0.01 by Cox regression model). A single patient in each group withdrew because of minor adverse effects. After two years of treatment, the proportion of patients with clinically overt disease decreased only in the ursodiol group (P < 0.02). The patients treated with ursodiol had significant improvements in serum levels of bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, cholesterol, and IgM (all P < 0.001); the antimitochondrial-antibody titer (P < 0.01); and the Mayo risk score (P < 0.001). Follow-up analysis of 95 liver-biopsy specimens showed a significant improvement in the mean histologic score (P < 0.002) and in all the characteristic histologic features except fibrosis only in the group given ursodiol.Conclusions. Ursodiol is a safe and effective treatment for primary biliary cirrhosis.