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

王璐; 孙可帅; 韩者艺; 郭长存; 贾桂; 高可娜; 张亚维; 韩英

doi:10.3969/j.issn.1001-5256.2018.11.020

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

DOI: 10.3969/j.issn.1001-5256.2018.11.020

空军军医大学西京消化病医院消化内科

基金项目:

国家自然科学基金(81600451,81770569)；陕西省自然科学基础研究计划(2017JQ8009)；

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中图分类号: R575.7
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出版历程
- 出版日期: 2018-11-20

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

Research funding:

摘要

摘要:
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χ2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...
- 肝硬化,胆汁性 /
- 熊脱氧胆酸 /
- 非诺贝特 /
- 治疗
Abstract:
Objective To investigate the clinical effect of fenofibrate combined with ursodeoxycholic acid ( UDCA) in the treatment of primary biliary cholangitis ( PBC) patients with poor response to UDCA alone. Methods A total of 67 PBC patients with poor response to UDCA who were treated in Xijing Hospital of Digestive Diseases, Air Force Medical University, from May 2009 to December 2017 were enrolled, and according to whether fenofibrate was used in addition, they were divided into combination treatment group with 33 patients and UDCA group with 34 patients. Related clinical data at baseline ( after one year of UDCA treatment) and at 6 and 12 months after treatment were collected, and the two groups were compared in terms of serum biochemical parameters, biochemical response, and GLOBE score after treatment. The t-test was used for comparison of normally distributed continuous data between two groups; the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups. The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. Results Compared with the UDCA group at 12 months after treatment, the combination treatment group had significant reductions in the serum levels of alkaline phosphatase ( ALP) , aspartate aminotransferase, alanine aminotransferase, 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 Barcelona criteria between the two groups ( t = 4. 349, P = 0. 037) . Compared with the UDCA group at 12 months after treatment, the combination 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 improve their blood biochemical parameters, especially the serum level of ALP. The combination treatment can also reduce the GLOBE score in patients with poor response and thus may help to improve long-term prognosis.
- liver cirrhosis, biliary /
- ursodesoxycholic acid /
- fenofibrate /
- therapy

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参考文献(28)

[1] HIRSCHFIELD GM, BEUERS U, CORPECHOT C, et al. EASL clinical practice guidelines:The diagnosis and management of patients with primary biliary cholangitis[J]. J Hepatol, 2017, 67 (1) :145-172.

[2] TRIVEDI PJ, LAMMERS WJ, van BUUREN HR, et al. Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis:A multicentre international study[J]. Gut, 2016, 65 (2) :321-329.

[3] SHI YW, YOU H. Therapeutic strategies for patients with primary biliary cholangitis and suboptimal response to ursodeoxycholic acid[J]. J Clin Hepatol, 2017, 33 (11) :2101-2104. (in Chinese) 施漪雯, 尤红.对熊去氧胆酸应答不佳的原发性胆汁性胆管炎治疗策略[J].临床肝胆病杂志, 2017, 33 (11) :2101-2104.

[4] ANGULO P, JORGENSEN RA, KEACH JC, et al. Oral budesonide in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid[J]. Hepatology, 2000, 31 (2) :318-323.

[5] NISANNE SG, MEENAKSHISUNDARAM A, CAROL JS, et al.Peroxisome proliferator-activated receptorαactivates human multidrug resistance transporter 3/ATP-binding cassette protein subfamily B4 transcription and increases rat biliary phosphatidylcholine secretion[J]. Hepatology, 2014, 59 (3) :1030-1042.

[6] AKIRA H, TADASHI I, MAKOTO N, et al. Anticholestatic effects of bezafibrate in patients with primary biliary cirrhosis treated with ursodeoxycholic acid[J]. Hepatology, 2013, 57 (5) :1931-1941.

[7] GHONEM NS, ASSIS DN, BOYER JL. Fibrates and cholestasis[J]. Hepatology, 2015, 62 (2) :635-643.

[8] NEVENS F, ANDREONE P, MAZZELLA G, et al. A placebocontrolled trial of obeticholic acid in primary biliary cholangitis[J].N Engl J Med, 2016, 375 (7) :631-643.

[9] CUPERUS FJ, HALILBASIC E, TRAUNER M. Fibrate treatment for primary biliary cirrhosis[J]. Curr Opin Gastroenterol, 2014, 30 (3) :279-286.

[10] GHONEM NS, BOYER JL. Fibrates as adjuvant therapy for chronic cholestatic liver disease:Its time has come[J]. Hepatology, 2013, 57 (5) :1691-1693.

[11] CHEUNG AC, LAPOINTE-SHAW L, KOWGIER M, et al. Combined ursodeoxycholic acid (UDCA) and fenofibrate in primary biliary cholangitis patients with incomplete UDCA response may improve outcomes[J]. Aliment Pharmacol Ther, 2016, 43 (2) :283-293.

[12] CORPECHOT C, CHAZOUILLèRES O, ROUSSEAU A, et al. A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis[J]. N Engl J Med, 2018, 378 (23) :2171-2181.

[13] DUAN W, OU X, WANG X, et al. Efficacy and safety of fenofibrate add-on therapy for patients with primary biliary cholangitis and a suboptimal response to UDCA[J]. Rev Esp Enferm Dig, 2018, 110 (9) :557-563.

[14] HAN XF, WANG QX, LIU Y, et al. Efficacy of fenofibrate in Chinese patients with primary biliary cirrhosis partially responding to ursodeoxycholic acid therapy[J]. J Digest Dis, 2012, 13 (4) :219-224.

[15] LINDOR KD, GERSHWIN ME, POUPON R, et al. AASLD practice guidelines:Primary biliary cirrhosis[J]. Hepatology, 2009, 50 (1) :291-308.

[16] CORPECHOT C, ABENAVOLI L, RABAHI N, et al. Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis[J]. Hepatology, 2008, 48 (3) :871-877.

[17] CORPECHOT C, CHAZOUILLERES O, POUPON R. Early primary biliary cirrhosis:Biochemical response to treatment and prediction of long-term outcome[J]. J Hepatol, 2011, 55 (6) :1361-1367.

[18] PARES A, CABALLERIA L, RODES J. Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic acid[J]. Gastroenterology, 2006, 130 (3) :715-720.

[19] LAMMERS WJ, HIRSCHFIELD GM, CORPECHOT C, et al. Development and validation of a scoring system to predict outcomes of patients with primary biliary cirrhosis receiving ursodeoxycholic acid therapy[J]. Gastroenterology, 2015, 149 (7) :1804-1812.e1804.

[20] SPRINGER J, CAUCH-DUDEK K, O'ROURKE K, et al. Asymptomatic primary biliary cirrhosis:A study of its natural history and prognosis[J]. Am J Gastroenterol, 1999, 94 (1) :47.

[21] MAHL TC, SHOCKCOR W, BOYER JL. Primary biliary cirrhosis:Survival of a large cohort of symptomatic and asymptomatic patients followed for 24 years[J]. J Hepatol, 1994, 20 (6) :707-713.

[22] CHRISTENSEN E, CROWE J, DONIACH D, et al. Clinical pattern and course of disease in primary biliary cirrhosis based on an analysis of 236 patients[J]. Gastroenterology, 1980, 78 (2) :236-246.

[23] de VRIES E, BEUERS U. Management of cholestatic disease in2017[J]. Liver Int, 2017, 37 (Suppl 1) :123-129.

[24] KUMAGI T, GUINDI M, FISCHER SE, et al. Baseline Ductopenia and treatment response predict long-term histological progression in primary biliary cirrhosis[J]. Am J Gastroenterol, 2010, 105 (10) :2186-2194.

[25] AZEMOTO N, KUMAGI T, ABE M, et al. Biochemical response to ursodeoxycholic acid predicts long-term outcome in Japanese patients with primary biliary cirrhosis[J]. Hepatol Res, 2011, 41 (4) :310-317.

[26] LAMMERT C, JURAN B, SCHLICHT E, et al. Biochemical response to ursodeoxycholic acid predicts survival in a North American cohort of primary biliary cirrhosis patients[J]. J Gastroenterol, 2014, 49 (10) :1414-1420.

[27] KUIPER EM, HANSEN BE, de VRIES RA, et al. Improved prognosis of patients with primary biliary cirrhosis that have a biochemical response to ursodeoxycholic acid[J]. Gastroenterology, 2009, 136 (4) :1281-1287.

[28] HEGADE VS, KHANNA A, WALKER LJ, et al. Long-term fenofibrate treatment in primary biliary cholangitis improves biochemistry but not the UK-PBC risk score[J]. Digest Dis Sci, 2016, 61 (10) :3037-3044.

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