Zhu Gui-Qi, Shi Ke-Qing, Huang Sha, Huang Gui-Qian, Lin Yi-Qian, Zhou Zhi-Rui, Braddock Martin, Chen Yong-Ping, Zheng Ming-Hua
From the Department of Infection and Liver Diseases (G-QZ, K-QS, SH, G-QH, Y-QL, Y-PC, M-HZ), Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University; School of the First Clinical Medical Sciences (G-QZ, SH); Institute of Hepatology (K-QS, Y-PC, M-HZ), Wenzhou Medical University; Renji School of Wenzhou Medical University (G-QH, Y-QL), Wenzhou; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, and Department of Oncology(Z-RZ), Shanghai Medical College, Fudan University, Shanghai, China; and Global Medicines Development (MB), AstraZeneca R&D, Alderley Park, United Kingdom.
Medicine (Baltimore). 2015 Mar;94(11):e609. doi: 10.1097/MD.0000000000000609.
Major ursodeoxycholic acid (UDCA)-based therapies for primary biliary cirrhosis (PBC) include UDCA only, or combined with either methotrexate (MTX), corticosteroids (COT), colchicine (COC), or bezafibrate (BEF). As the optimum treatment regimen is unclear and warrants exploration, we aimed to compare these therapies in terms of patient mortality or liver transplantation (MOLT) and adverse events (AE).PubMed, the Cochrane Library, and Scopus were searched for randomized controlled trials up to August 31, 2014. We estimated the hazard ratios (HRs) for MOLT and odds ratios (ORs) for AE. A sensitivity analysis based on the dose of UDCA was also executed.Thirty-one eligible articles were included. Compared with COT plus UDCA, UDCA (HR 0.38, 95% confidence interval [CI] 0.09-1.39), BEF plus UDCA (HR 0.29, 95% CI 0.02-4.83), COC plus UDCA (HR 0.39, 95% CI 0.07-2.25), MTX plus UDCA (HR 0.28, 95% CI 0.05-1.63), or OBS (HR 0.49, 95% CI 0.11-2.01) all provided an increased risk of MOLT. With respect to drug AE profile, although not differing appreciably, BEF plus UDCA was associated with more AEs compared with UDCA (OR 3.16, 95% CI 0.59-20.67), COT plus UDCA (OR 2.27, 95% CI 0.15-33.36), COC plus UDCA (OR 1.00, 95% CI 0.09-12.16), MTX plus UDCA (OR 2.03, 95% CI 0.23-17.82), or OBS (OR 3.00, 95% CI 0.53-20.75). The results of sensitivity analyses were highly consistent with previous analyses.COT plus UDCA was the optimal UDCA-based regimen for both MOLT and AEs. BEF plus UDCA was most likely to cause AEs, whereas monotherapy with UDCA and coadministriation of COT plus UDCA appeared to be associated with the fewest AEs for PBC treatment.
用于原发性胆汁性肝硬化(PBC)的主要基于熊去氧胆酸(UDCA)的疗法包括单用UDCA,或与甲氨蝶呤(MTX)、皮质类固醇(COT)、秋水仙碱(COC)或苯扎贝特(BEF)联合使用。由于最佳治疗方案尚不清楚且有待探索,我们旨在比较这些疗法在患者死亡率或肝移植(MOLT)以及不良事件(AE)方面的情况。检索了PubMed、考克兰图书馆和Scopus,查找截至2014年8月31日的随机对照试验。我们估计了MOLT的风险比(HRs)和AE的比值比(ORs)。还进行了基于UDCA剂量的敏感性分析。纳入了31篇符合条件的文章。与COT加UDCA相比,UDCA(HR 0.38,95%置信区间[CI] 0.09 - 1.39)、BEF加UDCA(HR 0.29,95% CI 0.02 - 4.83)、COC加UDCA(HR 0.39,95% CI 0.07 - 2.25)、MTX加UDCA(HR 0.28,95% CI 0.05 - 1.63)或观察(HR 0.49,95% CI 0.11 - 2.01)均增加了MOLT的风险。关于药物AE情况,虽然差异不明显,但与UDCA相比,BEF加UDCA与更多AE相关(OR 3.16,95% CI 0.59 - 20.67)、COT加UDCA(OR 2.27,95% CI 0.15 - 33.36)、COC加UDCA(OR 1.00,95% CI 0.09 - 12.16)、MTX加UDCA(OR 2.03,95% CI 0.23 - 17.82)或观察(OR 3.00,95% CI 0.53 - 20.75)。敏感性分析结果与先前分析高度一致。COT加UDCA是基于UDCA的MOLT和AE的最佳方案。BEF加UDCA最有可能引起AE,而UDCA单药治疗以及COT加UDCA联合使用似乎是PBC治疗中AE最少的方案。