原发性胆汁性胆管炎的药物治疗进展

郝娟; 吕靖; 邢枫; 杨全军; 刘成海

doi:10.3969/j.issn.1001-5256.2020.01.053

原发性胆汁性胆管炎的药物治疗进展

DOI: 10.3969/j.issn.1001-5256.2020.01.053

1. 上海中医药大学附属上海市中西医结合医院
2. 上海中医药大学附属曙光医院肝病研究所
3. 上海交通大学附属第六人民医院药剂科
4. 上海市中医临床重点实验室

基金项目:

国家自然科学基金资助项目(81803874)；

详细信息

中图分类号: R575.7
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- 被引次数: 0
出版历程
- 出版日期: 2020-01-20

Advances in drug therapy for primary biliary cholangitis

Shanghai Integrated Traditional Chinese and Western Medical Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China

Research funding:

摘要

摘要:
原发性胆汁性胆管炎是一种病因及发病机制尚不明确的胆汁淤积性肝病。熊去氧胆酸和奥贝胆酸是美国食品药品监督管理局批准使用的治疗药物,两者均有减轻肝内胆汁淤积的作用,但仍有部分患者对其治疗无生化应答,亟需探索新的治疗药物或方法。贝特类药物、免疫抑制剂及中医药对原发性胆汁性胆管炎患者有一定疗效,但临床安全性及作用机制尚需进一步研究。
- 肝硬化,胆汁性 /
- 药物疗法 /
- 中西医结合疗法
Abstract:
Primary biliary cholangitis(PBC) is a cholestatic liver disease with unclear etiology and pathogenesis. Ursodeoxycholic acid and obeticholic acid are the therapeutic drugs for PBC approved by the US Food and Drug Administration,both of which have the effect of alleviating intrahepatic cholestasis. However,some patients still have poor biochemical response to them,and it is urgent to explore new therapeutic drugs or methods. Fibrates,immunosuppressants,and traditional Chinese medicine have a certain effect in the treatment of patients with PBC,but further studies are needed to analyze their clinical safety and mechanism of action.
- liver cirrhosis,biliary /
- drug therapy /
- TCM WM therapy

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参考文献(52)

[1] LIEO A,COLAPIETRO F. Changes in the epidemiology of primary biliary cholangitis[J]. Clin Liver Dis,2018,22(3):429-441.

[2] CAREY EJ,ALI AH,LINDOR KD. Primary biliary cirrhosis[J].Lancet,2015,386(10003):1565-1575.

[3] KAPLAN MM,BONDER A,RUTHAZER R,et al. Methotrexate in patients with primary biliary cirrhosis who respond incompletely to treatment with ursodeoxycholic acid[J]. Dig Dis Sci,2010,55(11):3207-3217.

[4] POUPON R. Ursodeoxycholic acid and bile-acid mimetics as therapeutic agents for cholestatic liver diseases:An overview of their mechanisms of action[J]. Clin Res Hepatol Gastroenterol,2012,36(Suppl 1):s3-s12.

[5] TABIBIAN JH,LINDOR KD. Primary biliary cirrhosis:Safety and benefits of established and emerging therapies[J]. Expert Opin Drug Saf,2015,14(9):1435-1444.

[6] Chinese Society of Hepatology,Chinese Medical Association;Chinese Society of Gastroenterology,Chinese Medical Association; Chinese Society of Infectious Diseases,Chinese Medical Association. Consensus on the diagnosis and management of primary biliary cirrhosis(cholangitis)(2015)[J]. J Clin Hepatol,2015,31(12):1980-1988.(in Chinese)中华医学会肝病学分会，中华医学会消化病学分会，中华医学会感染病学分会．原发性胆汁性肝硬化(又名原发性胆汁性胆管炎)诊断和治疗共识(2015)[J]．临床肝胆病杂志，2015,31(12):1980-1988.

[7] LOCKE GR,THERNEAU TM,LUDWIG J,et al. Time course of histological progression in primary biliary cirrhosis[J]. Hepatology,1996,23(1):52-56.

[8] POUPON RE,POUPON R,BALKAU B. Ursodiol for the longterm treatment of primary biliary cirrhosis. The UDCA-PBC Study Group[J]. N Engl J Med,1994,330(19):1342-1347.

[9] ZHU JY,LI ZS,YAN W,et al. A two-year follow-up study on the efficacy of ursodeoxycholic acid on primary biliary cirrhosis in different stages[J]. Chin J Hepatol,2010,18(10):735-739.(in Chinese)朱疆依，李增山，晏伟，等．熊去氧胆酸治疗不同临床分期原发性胆汁性肝硬化的2年随访观察[J]．中华肝脏病杂志，2010,18(10):735-739.

[10] TANG R,WEI Y,LI Y,et al. Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy[J]. Gut,2018,67(3):534-541.

[11] DUSZYNSKI CC,AVATI V,LAPOINTE AP,et al. Near infrared spectroscopy reveals brain hypoxia and cerebrovascular dysregulation in primary biliary cholangitis[J]. Hepatology,2019.[Epub ahead of print]

[12] HARMS MH,van BUUREN HR,CORPECHOT C,et al. Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis[J]. J Hepatol,2019,71(2):357-365.

[13] 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.

[14] 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.

[15] 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.

[16] 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.

[17] HARMS MH,LAMMERS WJ,THORBURN D,et al. Major hepatic complications in ursodeoxycholic acid-treated patients with primary biliary cholangitis:Risk factors and time trends in incidence and outcome[J]. Am J Gastroenterol,2018,113(2):254-264.

[18] ORNOLFSSON KT,LUND SH,OLAFSSON S,et al. Biochemical response to ursodeoxycholic acid among PBC patients:a nationwide population-based study[J]. Scand J Gastroenterol,2019,54(5):609-616.

[19] ter BORG PC,SCHALM SW,HANSEN BE,et al. Prognosis of ursodeoxycholic Acid-treated patients with primary biliary cirrhosis. Results of a 10-yr cohort study involving 297 patients[J]. Am J Gastroenterol,2006,101(9):2044-2050.

[20] SURAWEERA D,RAHAL H,JIMENEZ M,et al. Treatment of primary biliary cholangitis ursodeoxycholic acid non-responders:A systematic review[J]. Liver Int,2017,37(12):1877-1886.

[21] MARKHAM A,KEAM SJ. Obeticholic acid:First global approval[J]. Drugs,2016,76(12):1221-1226.

[22] NEUSCHWANDER-TETRI BA,LOOMBA R,SANYAL AJ,et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic,non-alcoholic steatohepatitis(FLINT):A multicentre,randomised,placebo-controlled trial[J]. Lancet,2015,385(9972):956-965.

[23] ZHOU J,HUANG N,GUO Y,et al. Combined obeticholic acid and apoptosis inhibitor treatment alleviates liver fibrosis[J]. Acta Pharm Sin B,2019,9(3):526-536.

[24] HIRSCHFIELD GM,MASON A,LUKETIC V,et al. Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid[J]. Gastroenterology,2015,148(4):751-761. e8.

[25] 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.

[26] SAMUR S,KLEBANOFF M,BANKEN R,et al. Long-term clinical impact and cost-effectiveness of obeticholic acid for the treatment of primary biliary cholangitis[J]. Hepatology,2017,65(3):920-928.

[27] GAO XS,ZHANG YN,LIU T,et al. Osteoporosis in patients with primary biliary cirrhosis[J/CD]. Chin J Liver Dis(Electr Version),2018,10(3):56-60.(in Chinese)高学松，张耀南，刘婷，等．原发性胆汁性肝硬化患者合并骨质疏松症临床研究[J/CD]．中国肝脏病杂志(电子版)，2018,10(3):56-60.

[28] LEUSCHNER M,MAIER KP,SCHLICHTING J,et al. Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis:Results of a prospective double-blind trial[J]. Gastroenterology,1999,117(4):918-925.

[29] 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.

[30] HEMPFLING W,GRUNHAGE F,DILGER K,et al. Pharmacokinetics and pharmacodynamic action of budesonide in earlyand late-stage primary biliary cirrhosis[J]. Hepatology,2003,38(1):196-202.

[31] SILVEIRA MG,LINDOR KD. Obeticholic acid and budesonide for the treatment of primary biliary cirrhosis[J]. Expert Opin Pharmacother,2014,15(3):365-372.

[32] GONG Y,CHRISTENSEN E,GLUUD C. Azathioprine for primary biliary cirrhosis[J]. Cochrane Database Syst Rev,2007,3:CD006000.

[33] TALWALKAR JA,ANGULO P,KEACH JC,et al. Mycophenolate mofetil for the treatment of primary biliary cirrhosis in patients with an incomplete response to ursodeoxycholic acid[J]. J Clin Gastroenterol,2005,39(2):168-171.

[34] GILJACA V,POROPAT G,STIMAC D,et al. Methotrexate for primary biliary cirrhosis[J]. Cochrane Database Syst Rev,2010,5:CD004385.

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

[36] HONDA A,IKEGAMI T,NAKAMUTA M,et al. Anticholestatic effects of bezafibrate in patients with primary biliary cirrhosis treated with ursodeoxycholic acid[J]. Hepatology,2013,57(5):1931-1941.

[37] 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.

[38] WANG L,CHANG YH,HAN Y. The pathogenesis and treatment progress of primary biliary cholangitis[J]. Int J Dig Dis,2019,39(2):81-85.(in Chinese)王璐，常英昊，韩英．原发性胆汁性胆管炎的发病机制及治疗进展[J]．国际消化病杂志，2019,39(2):81-85.

[39] FENG BL,YU HH,SHEN W. Ursodeoxycholic acid combined with bezafibrate in the treatment of refractory primary biliary cholangitis:A meta-analysis[J]. Chin J Hepatol,2019,27(4):304-311.(in Chinese)奉白蕾，俞慧宏，沈薇．熊去氧胆酸联合苯扎贝特治疗难治性原发性胆汁性胆管炎的Meta分析[J]．中华肝脏病杂志，2019,27(4):304-311.

[40] CORPECHOT C,CHAZOUILLERES 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.

[41] HONDA A,TANAKA A,KANEKO T,et al. Bezafibrate improves GLOBE and UK-PBC scores and long-term outcomes in patients with primary biliary cholangitis[J]. Hepatology,2019.[Epub ahead of print]

[42] REIG A,SESE P,PARES A. Effects of bezafibrate on outcome and pruritus in primary biliary cholangitis with suboptimal ursodeoxycholic acid response[J]. Am J Gastroenterol,2018,113(1):49-55.

[43] WANG L,SUN KS,HAN ZY,et al. Clinical effect of fenofibrate combined with ursodeoxycholic acid in treatment of primary biliary cholangitis patients with poor response to ursodeoxycholic acid alone[J]. J Clin Hepatol,2018,34(11):2368-2372.(in Chinese)王璐，孙可帅，韩者艺，等．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[J]．临床肝胆病杂志，2018,34(11):2368-2372.

[44] CHENG LB,WU F. Clinical analysis of traditional Chinese medicine for primary biliary cirrhosis[J]. Hubei J Tradit Chin Med,2011,33(2):13-14.(in Chinese)程良斌，吴凡．原发性胆汁性肝硬化中医临床分析[J]．湖北中医杂志，2011,33(2):13-14.

[45] ZHANG N,GONG M,ZHOU SN,et al. A literature retrieval on classification and characteristics of traditional Chinese medicine syndromes in patients with primary biliary cirrhosis[J]. J Prac Hepatol,2013,16(5):445-447.(in Chinese)张宁，宫嫚，周双男，等．原发性胆汁性肝硬化中医证候分型文献分析[J]．实用肝脏病杂志，2013,16(5):445-447.

[46] LIU B,CHEN BH. Tradition Chinese medicine identification and progress in the treatment of primary biliary cirrhosis[J].Shanghai Med Pharm J,2017,38(12):32-34,49.(in Chinese)刘贝，陈碧华．原发性胆汁性肝硬化的中医辨识及治疗进展[J]．上海医药，2017,38(12):32-34,49.

[47] WU SC. Professor Chang Zhanjie’s experience in treating primary biliary cirrhosis with integrated Chinese and Western medicine[J]. Mod Tradit Chin Med,2011,31(5):9-11.(in Chinese)吴绍从．常占杰教授中西医结合治疗原发性胆汁性肝硬化的经验[J]．现代中医药，2011,31(5):9-11.

[48] CHEN JL,YANG X,ZHANG Q,et al. Effect of ursodeoxycholic acid with traditional Chinese medicine on biochemical response in patients with primary biliary cholangitis:A realworld cohort study[J]. Chin J Hepatol,2018,26(12):909-915.(in Chinese)陈佳良，杨雪，张群，等．熊去氧胆酸联合中药治疗对原发性胆汁性胆管炎患者生物化学应答的影响:一项基于真实世界的队列研究[J]．中华肝脏病杂志，2018,26(12):909-915.

[49] YANG L,LI Y,YUAN XX,et al. Effect of Yangyin Tongluo Decoction on primary biliary cholangitis and its influence on cytokines[J]. Chin J Integr Trad West Med Dig,2017,25(9):646-650,655.(in Chinese)杨磊，李莹，袁星星，等．养阴通络汤对原发性胆汁性胆管炎临床疗效及对细胞因子的影响[J]．中国中西医结合消化杂志，2017,25(9):646-650,655.

[50] MA WT,CHEN DK. Immunological abnormalities in patients with primary biliary cholangitis[J]. Clin Sci(Lond),2019,133(6):741-760.

[51] LI Y,LI B,YOU Z,et al. Cytotoxic KLRG1 expressing lymphocytes invade portal tracts in primary biliary cholangitis[J].J Autoimmun,2019,103:102293.

[52] VIGNOLI A,ORLANDINI B,TENORI L,et al. Metabolic signature of primary biliary cholangitis and its comparison with celiac disease[J]. J Proteome Res,2019,18(3):1228-1236.

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