不同剂量熊去氧胆酸治疗原发性硬化性胆管炎疗效比较的meta分析

目的系统评价不同剂量的熊去氧胆酸(ursodeoxycholic acid,UDCA)治疗原发性硬化性胆管炎(primary sclerosing cholangitis,PSC)的临床疗效。方法从PubMed、Embase、中国知网和万方等数据库中检索相关文献,按照低(13~15 mg/kg)、中(17~23 mg/kg)及高(28~30 mg/kg)剂量分层,使用Cochrane协作网提供的Review Manager 5.3软件进行meta分析。结果本研究最终纳入9篇相关的随机对照研究,样本量840例。meta分析显示,熊去氧胆酸能够降低碱性磷酸酶(alkaline phosphatase,ALP)标准化均数差(standardized mean difference,SMD)=-0.50,95%可信区间(confidence interval,CI):-0.70^-0.31)]和谷草转氨酶(aspartate aminotransferase,AST),SMD=-0.59,95%CI:-0.85^-0.32]水平,改善肝功能。亚组分析显示,低剂量的熊去氧胆酸可能降低结直肠肿瘤的发生率比值比(odds ratio,OR)=0.22,95%CI:0.05~0.94];高剂量的熊去氧胆酸反而会增加肝移植(OR=2.21,95%CI:1.12~4.36)、死亡或肝移植(OR=1.90,95%CI:1.08~3.34)、静脉曲张(OR=4.08,95%CI:1.87~8.91)及结直肠肿瘤(OR=5.25,95%CI:1.24~22.24)等不良事件的发生风险。结论低剂量的熊去氧胆酸可降低PSC患者ALP及AST水平,改善肝功能,预防结直肠肿瘤的发生;高剂量的熊去氧胆酸反而会增加静脉曲张及结直肠肿瘤等严重不良事件的发生风险。

Efficacy of different doses of ursodeoxycholic acid in the treatment of primary sclerosing cholangitis:a meta-analysis

Objective To systematically evaluate the clinical efficacy of different doses of ursodeoxycholic acid(UDCA) in the treatment of primary sclerosing cholangitis(PSC).Methods The relevant literatures were searched from the databases of PubMed,Embase,China national knowledge infrastructure and Wanfang database,and stratified according to low(13~15 mg/kg),medium(17~23 mg/kg) and high(28~30 mg/kg) doses.Meta-analysis was performed using Review Manager 5.3 software from the Cochrane Collaboration.Results The study finally included 9 related randomized controlled trials with a sample size of 840.The meta-analysis showed that UDCA can reduce ALPSMD=-0.50,95% confidence interval(CI):-0.70^-0.31]and AST(SMD=-0.59,95%CI:-0.85^-0.32) to improve liver function.Subgroup analysis showed that low doses of UDCA may reduce the incidence of colorectal tumorsodds ratio(OR)=0.22,95%CI:0.05~0.94];high doses of UDCA may increase the risk of adverse events such as liver transplantation(OR=2.21,95%CI:1.12~4.36),death or liver transplantation(OR=1.90,95%CI:1.08~3.34),varices(OR=4.08,95%CI:1.87~8.91) and colorectal tumors(OR=5.25,95%CI:1.24~22.24).Conclusion Low dose of UDCA can reduce ALP and AST levels,improve liver function and prevent colorectal tumors in patients with PSC.High dose of UDCA may increase the risk of serious adverse events such as varicose veins and colorectal tumors.