High-dose ursodeoxycholic acid in primary sclerosing cholangitis:: A 5-year multicenter, randomized, controlled study
High-dose ursodeoxycholic acid in primary sclerosing cholangitis:: A 5-year multicenter, randomized, controlled study
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DOI：
10.1053/j.gastro.2005.08.017
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发表时间：
2005-11-01
期刊：
影响因子：
29.4
通讯作者：
Broomé, U
中科院分区：
文献类型：
--
作者：
Olsson, R;Boberg, KM;Broomé, U
背景与目的：原发性硬化性胆管炎目前尚无有效的药物治疗。本研究旨在研究比以前使用的剂量更高的熊去氧胆酸对这种疾病的生存率、症状、生物化学和生活质量的影响。方法：在三级和二级消化科进行了一项随机安慰剂对照研究。共有219例患者随机接受17 - 23 mg/kg体重/天的熊去氧胆酸（n = 110）或安慰剂（n = 109）治疗5年。随访数据可从97例随机分配至熊去氧胆酸组和101例随机分配至安慰剂组的患者中获得。生活质量的评估使用医疗结果研究36项健康调查简表。结果如下：熊去氧胆酸组97例患者中有7例（7.2%）发生了联合终点“死亡或肝移植”，而安慰剂组101例患者中有11例（10.9%）发生了联合终点“死亡或肝移植”（P = 0.368; 95%置信区间，-12.2%至4.7%）。肝移植作为单一终点的发生率显示熊去氧胆酸治疗组的阳性趋势相似（5/97 [5.2%] vs 8/101 [7.9%]; 95%置信区间，-10.4%至4.6%）。3例熊去氧胆酸组和4例安慰剂组患者死于胆管癌，1例安慰剂组患者死于肝衰竭。碱性磷酸酶和丙氨酸氨基转移酶在前6个月有下降的趋势。两组在症状或生活质量方面没有差异。血清熊去氧胆酸浓度分析没有证据表明不依从可能影响结果。结论：这项研究发现，与以前使用的剂量相比，更高剂量的熊去氧胆酸对原发性硬化性胆管炎患者的生存率或胆管癌的预防没有统计学显著的有益作用。
Background & Aims: There is no medical treatment of proven benefit for primary sclerosing cholangitis. This study aimed at studying the effect of a higher dose of ursodeoxycholic acid than previously used on survival, symptoms, biochemistry, and quality of life in this disease. Methods: A randomized placebo-controlled study was performed in tertiary and secondary gastroenterology units. A total of 219 patients were randomized to 17 to 23 mg/kg body weight per day of ursodeoxycholic acid (n = 110) or placebo (n = 109) for 5 years. Follow-up data are available from 97 patients randomized to ursodeoxycholic acid and for 101 randomized to placebo. Quality of life was assessed by using the Medical Outcomes Study 36-item Short-Form Health Survey. Results: The combined end point "death or liver transplantation" occurred in 7 of 97 (7.2%) patients in the ursodeoxycholic acid group vs 11 of 101 (10.9%) patients in the placebo group (P = .368; 95% confidence interval, -12.2% to 4.7%). The occurrence of liver transplantation as a single end point showed a similar positive trend for ursodeoxycholic acid treatment (5/97 [5.2%] vs 8/101 [7.9%]; 95% confidence interval, -10.4% to 4.6%). Three ursodeoxycholic acid and 4 placebo patients died from cholangiocarcinoma, and I placebo patient died from liver failure. Alkaline phosphatase and alanine aminotransferase tended to decrease during the first 6 months. There were no differences between the 2 groups in symptoms or quality of life. Analyses of serum ursodeoxycholic acid concentration gave no evidence that noncompliance may have influenced the results. Conclusions: This study found no statistically significant beneficial effect of a higher dose of ursodeoxycholic acid than previously used on survival or prevention of cholangiocarcinoma in primary sclerosing cholangitis.