Lindor K D, Dickson E R, Baldus W P, Jorgensen R A, Ludwig J, Murtaugh P A, Harrison J M, Wiesner R H, Anderson M L, Lange S M
Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota.
Gastroenterology. 1994 May;106(5):1284-90. doi: 10.1016/0016-5085(94)90021-3.
BACKGROUND/AIMS: A double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) was conducted in 180 patients with primary biliary cirrhosis (PBC) to define the efficacy and safety of UDCA. Efficacy was assessed by time to treatment failure defined as death; liver transplantation; histological progression; development of varices, ascites, or encephalopathy; doubling of total serum bilirubin levels; progression of fatigue or pruritus; drug toxicity; or voluntary withdrawal.
Patients with well-defined PBC underwent complete history, physical examination, liver chemistries, ultrasonography, upper endoscopy, and liver biopsy at entry as well as at 2 years. Liver chemistries were determined every 3 months.
In patients receiving UDCA, treatment failure was delayed compared with the placebo-treated group (P = 0.0003, log rank test). Seven patients receiving UDCA died or required transplantation compared with 12 in the placebo group (P = 0.18). No patients discontinued UDCA because of side effects of toxicity.
UDCA was extraordinarily safe and well tolerated, and its use was associated with delayed progression of the disease as defined in this study. However, the lack of effects on symptoms, histology, and the need for liver transplantation or survival indicate that further evaluation is necessary to determine the ultimate role of UDCA in the treatment of PBC.
背景/目的:对180例原发性胆汁性肝硬化(PBC)患者进行了一项熊去氧胆酸(UDCA)的双盲、安慰剂对照试验,以确定UDCA的疗效和安全性。疗效通过治疗失败时间来评估,治疗失败定义为死亡、肝移植、组织学进展、出现静脉曲张、腹水或肝性脑病、血清总胆红素水平翻倍、疲劳或瘙痒进展、药物毒性或自愿退出。
确诊为PBC的患者在入组时以及2年时接受了完整的病史、体格检查、肝脏生化检查、超声检查、上消化道内镜检查和肝活检。每3个月测定一次肝脏生化指标。
与安慰剂治疗组相比,接受UDCA治疗的患者治疗失败时间延迟(P = 0.0003,对数秩检验)。接受UDCA治疗的7例患者死亡或需要移植,而安慰剂组为12例(P = 0.18)。没有患者因毒性副作用而停用UDCA。
UDCA非常安全且耐受性良好,根据本研究定义,其使用与疾病进展延迟相关。然而,对症状、组织学以及肝移植需求或生存率缺乏影响表明,有必要进一步评估以确定UDCA在PBC治疗中的最终作用。