非诺贝特联合熊去氧胆酸治疗单用熊去氧胆酸应答不佳的原发性胆汁性胆管炎患者的效果评价

Clinical effect of fenofibrate combined with ursodeoxycholic acid in treatment of primary biliary cholangitis patients with poor response to ursodeoxycholic acid alone

目的探讨非诺贝特联合熊去氧胆酸(UDCA)治疗单用熊去氧胆酸应答不佳的原发性胆汁性胆管炎(PBC)患者的效果。方法选取2009年5月-2017年12月于空军军医大学西京消化病医院就诊的UDCA应答不佳PBC患者67例,根据是否加用非诺贝特分为联合治疗组33例、UDCA单药治疗组34例。收集2组患者基线(UDCA治疗1年时)和治疗后第6、12个月的临床资料,对比2组患者治疗后血清生化指标、生化应答反应、GLOBE评分。正态分布的计量资料2组间比较采用t检验;非正态分布的计量资料2组间比较采用Mann-Whitney U检验。计数资料2组间比较采用χ~2检验或Fisher精确检验分析。结果治疗后第12个月,联合治疗组血清ALP、AST、ALT和GGT水平较单药UDCA组明显降低,差异均有统计学意义(t值分别为3. 465、2. 406、2. 057、3. 208,P值分别为<0. 001、0. 019、0. 002、0. 044)。根据巴塞罗那标准、ParisⅠ、Ⅱ标准,联合治疗组治疗12个月后的生化应答率分别为54. 5%(18/15)、36. 4%(12/21)、34. 3%(11/22),巴塞罗那标准的评价结果与单药治疗组比较差异有统计学差异(t=4. 349,P=0. 037)。治疗第12个月时,联合治疗组的GLOBE评分明显低于单药治疗组[0. 921(0. 519~1. 657) vs 0. 498(-0. 026~1. 027),Z=-2. 007,P=0. 045],5、10、15年非肝移植生存率明显高于单药治疗组,差异有统计学意义(Z值分别为-2. 000、-2. 004、-2. 009,P值分别为0. 045、0. 045、0. 043)。结论非诺贝特联合UDCA可以明显改善UDCA应答不佳患者的血生化指标,尤其是血清ALP水平;同时可降低应答不佳者的GLOBE评分,可能有助于改善远期预后。

Objective To investigate the clinical effect of fenofibrate combined with ursodeoxycholic acid （ UDCA）in the treatment of primary biliary cholangitis （ PBC）patients with poor response to UDCA alone. Methods A total of 67 PBC patients with poor response to UDCA who were treated in Xijing Hospital of Digestive Diseases,Air Force Medical University,from May 2009 to December 2017 were enrolled,and according to whether fenofibrate was used in addition,they were divided into combination treatment group with 33 patients andUDCA group with 34 patients. Related clinical data at baseline （ after one year of UDCA treatment）and at 6 and 12 months after treatmentwere collected,and the two groups were compared in terms of serum biochemical parameters,biochemical response,and GLOBE score aftertreatment. The t - test was used for comparison of normally distributed continuous data between two groups;the Mann -Whitney U test wasused for comparison of continuous data with skewed distribution between two groups. The chi - square test or the Fisher′s exact test was usedfor comparison of categorical data between groups. Results Compared with the UDCA group at 12 months after treatment,the combinationtreatment group had significant reductions in the serum levels of alkaline phosphatase （ ALP） ,aspartate aminotransferase,alanine aminotransferase,and gamma - glutamyl transpeptidase （ t = 3 465, 2 406, 2 057 and 3 208,P 〈 0. 001 and P = 0. 019,0. 002,and 0. 044） .According to the Barcelona criteria and the Paris I / II criteria,the combination treatment group had a biochemical response rate of 54. 5%（ 18 / 15） ,36. 4% （ 12 / 21） ,and 34. 3% （ 11 / 22） ,respectively,and there was a significant difference in the evaluation results of the Barcelona criteria between the two groups （ t = 4 349, P = 0. 037） . Compared with the UDCA group at 12 months after treatment,the combination treatment group had a significantly lower GLOBE score[ 0 921（ 0 519 ～ 1 657） vs 0 498（- 0 026 ～ 1 027） , Z = - 2 007, P = 0 045]and significantly higher 5 - ,10 - ,and 15 - year transplant - free survival rates （ Z = - 2 000,- 2 004 and - 2 009,P = 0. 045,0 045,and 0 043） . Conclusion In patients with poor response to UDCA alone,fenofibrate combined with UDCA can significantly improve their blood biochemical parameters,especially the serum level of ALP. The combination treatment can also reduce the GLOBE score inpatients with poor response and thus may help to improve long - term prognosis.