Heathcote E J, Cauch-Dudek K, Walker V, Bailey R J, Blendis L M, Ghent C N, Michieletti P, Minuk G Y, Pappas S C, Scully L J
Department of Medicine, University of Toronto, Ontario, Canada.
Hepatology. 1994 May;19(5):1149-56.
Ursodeoxycholic acid, a dihydroxyl bile acid normally present in human beings in minimal amounts, becomes incorporated into the bile salt pool when taken orally. In cholestasis, bile acids are retained in the liver and are hepatotoxic. Ursodeoxycholic acid is the least-known hepatotoxic bile acid, has choleretic properties and is reported to benefit patients with chronic cholestasis. In a nationwide Canadian controlled trial, 222 patients with primary biliary cirrhosis were treated with ursodeoxycholic acid (14 mg/kg/body wt/day) or placebo for 24 mo. Only patients with a diagnosis confirmed by liver biopsy and serum positive for antimitochondrial antibodies were enrolled; 88% were symptomatic on entry. The primary outcome measure was percent change in total serum bilirubin from baseline to final follow-up. Treated patients (111) and controls (111) were comparable with regard to age, gender, biochemical parameters and liver histological condition. Although treatment was not associated with any improvement in symptoms, ursodeoxycholic acid therapy caused the bilirubin to fall significantly within the first 3 mo of therapy (p < 0.001). Significant falls in serum alkaline phosphatase, aminotransferases, cholesterol and IgM levels were also noted in the treated group. Improvement in some histological features was observed but there was no difference between the groups in the number of patients who reached the endpoints of death or liver transplantation. Ursodeoxycholic acid, given to patients with primary biliary cirrhosis, leads to an improvement in serum markers of cholestasis. A larger sample size is needed to determine whether ursodeoxycholic acid therapy has a beneficial effect on the survival of patients with primary biliary cirrhosis.
熊去氧胆酸是一种二羟基胆汁酸，正常情况下在人体内含量极少，口服后会融入胆盐池。在胆汁淤积时，胆汁酸会潴留在肝脏中，具有肝毒性。熊去氧胆酸是最不为人知的具有肝毒性的胆汁酸，具有利胆特性，据报道对慢性胆汁淤积患者有益。在一项加拿大全国性对照试验中，222例原发性胆汁性肝硬化患者接受熊去氧胆酸（14毫克/千克体重/天）或安慰剂治疗24个月。仅纳入经肝活检确诊且抗线粒体抗体血清阳性的患者；88%的患者在入组时有症状。主要结局指标是从基线到最终随访时总血清胆红素的变化百分比。治疗组患者（111例）和对照组患者（111例）在年龄、性别、生化参数和肝脏组织学状况方面具有可比性。虽然治疗与症状的任何改善均无关联，但熊去氧胆酸治疗在治疗的前3个月内使胆红素显著下降（p<0.001）。治疗组还观察到血清碱性磷酸酶、转氨酶、胆固醇和IgM水平显著下降。观察到一些组织学特征有所改善，但在达到死亡或肝移植终点的患者数量上两组之间没有差异。给予原发性胆汁性肝硬化患者熊去氧胆酸可使胆汁淤积的血清标志物得到改善。需要更大的样本量来确定熊去氧胆酸治疗对原发性胆汁性肝硬化患者的生存是否具有有益作用。
