van Hoogstraten H J, Wolfhagen F H, van de Meeberg P C, Kuiper H, Nix G A, Becx M C, Hoek A C, van Houte D P, Rijk M C, Salemans J M, Scherpenisse J, Schrijver M, Smit A M, Spoelstra P, Stadhouders P H, Tan T G, Hop W C, ten Kate F J, vanBerge-Henegouwen G P, Schalm S W, van Buuren H R
Erasmus University Hospital Rotterdam, The Netherlands.
J Hepatol. 1998 Sep;29(3):417-23. doi: 10.1016/s0168-8278(98)80059-7.
BACKGROUND/AIMS: Ursodeoxycholic acid has been reported to be of potential benefit for primary sclerosing cholangitis but little is known about the long-term biochemical, histological and radiological efficacy or the optimum frequency of ursodeoxycholic acid administration.
A 2-year multicentre randomised controlled trial was initiated to assess the effects of ursodeoxycholic acid (10 mg kg(-1).d(-1), given in either single or multiple daily doses, on symptoms, serum liver tests, cholangiographic and histological findings and the occurrence of treatment failure. Liver biopsies were taken and endoscopic retrograde cholangiography was performed at entry and after 2 years; follow-up examinations were at 3-month intervals. Treatment failure was defined as death, liver transplantation, 4-fold increase in serum bilirubin, variceal bleeding, de novo ascites or cholangitis. Actuarial survival was compared with predicted survival using the revised Mayo natural history model for primary sclerosing cholangitis.
Forty-eight patients were enrolled. In one case, ursodeoxycholic acid had to be discontinued because of gastro-intestinal complaints. No other side-effects were observed. After 2 years of follow-up, treatment was not associated with a beneficial effect on either symptoms or liver histology. Serum liver tests (alkaline phosphatase, y-glutamyl transferase, aspartate aminotransferase) improved significantly in both groups, while serum bilirubin (which was near normal at entry) and IgG remained stable. No major changes in radiographic bile duct appearance seemed to be present. After 2 years, actuarial survival was 91% (95 CI 83%-99%), which is comparable to the predicted 97% survival rate. Treatment failure occurred in 15% of cases. No significant differences in any of the study endpoints (symptoms, serum liver tests, cholangiographic findings, histology, disease progression) were found between the two groups.
Ursodeoxycholic acid is well tolerated in primary sclerosing cholangitis. Significant effects on biochemical parameters were found and symptoms, bilirubin and histology did not deteriorate. No advantage of a multiple daily dose over a single dose was observed.
背景/目的：据报道，熊去氧胆酸对原发性硬化性胆管炎可能有益，但对于其长期的生化、组织学和放射学疗效或熊去氧胆酸给药的最佳频率知之甚少。
启动了一项为期2年的多中心随机对照试验，以评估熊去氧胆酸（10mg·kg⁻¹·d⁻¹，每日单次或多次给药）对症状、血清肝功能检查、胆管造影和组织学结果以及治疗失败发生率的影响。在入组时和2年后进行肝活检并进行内镜逆行胆管造影；随访检查每3个月进行一次。治疗失败定义为死亡、肝移植、血清胆红素升高4倍、静脉曲张出血、新发腹水或胆管炎。使用修订后的原发性硬化性胆管炎梅奥自然史模型将实际生存率与预测生存率进行比较。
48例患者入组。1例患者因胃肠道不适不得不停用熊去氧胆酸。未观察到其他副作用。经过2年的随访，治疗对症状或肝脏组织学均无有益影响。两组的血清肝功能检查（碱性磷酸酶、γ-谷氨酰转移酶、天冬氨酸转氨酶）均有显著改善，而血清胆红素（入组时接近正常）和IgG保持稳定。胆管造影显示胆管外观似乎没有重大变化。2年后，实际生存率为91%（95%CI 83%-99%），与预测的97%生存率相当。15%的病例出现治疗失败。两组在任何研究终点（症状、血清肝功能检查、胆管造影结果、组织学、疾病进展）方面均未发现显著差异。
原发性硬化性胆管炎患者对熊去氧胆酸耐受性良好。发现对生化参数有显著影响，症状、胆红素和组织学未恶化。未观察到每日多次给药比单次给药有优势。
