中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

原发性胆汁性胆管炎药物治疗的基本观念及进展

金倩雯 涂传涛

引用本文:
Citation:

原发性胆汁性胆管炎药物治疗的基本观念及进展

DOI: 10.3969/j.issn.1001-5256.2017.08.039
详细信息
  • 中图分类号: R575.22

Pharmacotherapy for primary biliary cholangitis: basic concepts and research advances

  • 摘要: 原发性胆汁性胆管炎(PBC)是一种原因不明的慢性进行性胆汁淤积性肝病,其特征性表现为高特异性的血清抗线粒体抗体和免疫介导的肝内小胆管非化脓性破坏性炎症,从而导致汇管区炎症与纤维化,最终发展为肝硬化及肝衰竭。熊去氧胆酸(UDCA)是目前唯一公认的用于治疗PBC的药物,推荐剂量为1315 mg·kg-1·d-1,UDCA治疗获得生化应答患者的生存率可明显改善。然而,大约40%的PBC患者对UDCA治疗无应答,这部分存在疾病进展风险的患者亟需其他药物治疗。基于近年临床研究资料与指南,总结了目前PBC药物治疗的基本观念及最新进展,并展望正在临床试验的治疗新药,以期为UDCA治疗应答欠佳的PBC患者带来新的希望。

     

  • [1]CAREY EJ, ALI AH, LINDOR KD.Primary biliary cirrhosis[J].Lancet, 2015, 386 (10003) :1565-1575.
    [2]CZUL F, LEVY C.Novel therapies on primary biliary cirrhosis[J].Clin Liver Dis, 2016, 20 (1) :113-130.
    [3]DYSON JK, HIRSCHFIELD GM, ADAMS DH, et al.Novel therapeutic targets in primary biliary cirrhosis[J].Nat Rev Gastroenterol Hepatol, 2015, 12 (3) :147-158.
    [4]WANG L, GERSHWIN ME, WANG FS.Primary biliary cholangitis in China[J].Curr Opin Gastroenterol, 2016, 32 (3) :195-203.
    [5]MAYO MJ.Natural history of primary biliary cirrhosis[J].Clin Liver Dis, 2008, 12 (2) :277-288.
    [6]European Association for the Study of the Liver.EASL Clinical Practice Guidelines:management of cholestatic liver diseases[J].J Hepatol, 2009, 51 (2) :237-267.
    [7]TRIVEDI PJ, CORPECHOT C, PARES A, et al.Risk stratification in autoimmune cholestatic liver diseases:opportunities for clinicians and trialists[J].Hepatology, 2016, 63 (2) :644-659.
    [8]de VRIES E, BEUERS U.Management of cholestatic disease in2017[J].Liver Int, 2017, 37 (Suppl 1) :123-129.
    [9]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.
    [10]BEUERS U, TRAUNER M, JANSEN P, et al.New paradigms in the treatment of hepatic cholestasis:from UDCA to FXR, PXR and beyond[J].J Hepatol, 2015, 62 (1 Suppl) :s25-s37.
    [11]GOULIS J, LEANDRO G, BURROUGHS AK.Randomised controlled trials of ursodeoxycholic-acid therapy for primary biliary cirrhosis:a meta-analysis[J].Lancet, 1999, 354 (9184) :1053-1060.
    [12]POUPON RE, BALKAU B, ESCHWGE E, et al.A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis.UDCA-PBC Study Group[J].N Engl J Med, 1991, 324 (22) :1548-1554.
    [13]HUET PM, VINCENT C, DESLAURIER J, et al.Portal hypertension and primary biliary cirrhosis:effect of long-term ursodeoxycholic acid treatment[J].Gastroenterology, 2008, 135 (5) :1552-1560.
    [14]BATTS KP, JORGENSEN RA, DICKSON ER, et al.Effects of ursodeoxycholic acid on hepatic inflammation and histological stage in patients with primary biliary cirrhosis[J].Am J Gastroenterol, 1996, 91 (11) :2314-2317.
    [15]COMBES B, CARITHERS RL Jr, MADDREY WC, et al.A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis[J].Hepatology, 1995, 22 (3) :759-766.
    [16]POUPON RE, LINDOR KD, PARS A, et al.Combined analysis of the effect of treatment with ursodeoxycholic acid on histologic progression in primary biliary cirrhosis[J].J Hepatol, 2003, 39 (1) :12-16.
    [17]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.
    [18]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.
    [19]PARS A, CABALLERA L, RODS J.Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic Acid[J].Gastroenterology.2006, 130 (3) :715-720.
    [20]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.
    [21]CORPECHOT C, CHAZOUILLRES 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.
    [22]ANGULO P, DICKSON ER, THERNEAU TM, et al.Comparison of three doses of ursodeoxycholic acid in the treatment of primary biliary cirrhosis:a randomized trial[J].J Hepatol, 1999, 30 (5) :830-835.
    [23]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.
    [24]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.
    [25]ANGULO P, LINDOR KD, THERNEAU TM, et al.Utilization of the Mayo risk score in patients with primary biliary cirrhosis receiving ursodeoxycholic acid[J].Liver, 1999, 19 (2) :115-121.
    [26]LAMMERS WJ, van BUUREN HR, HIRSCHFIELD GM, et al.Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis:an international follow-up study[J].Gastroenterology, 2014, 147 (6) :1338-1349.
    [27]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.
    [28]GONG Y, HUANG Z, CHRISTENSEN E, et al.Ursodeoxycholic acid for patients with primary biliary cirrhosis:an updated systematic review and meta-analysis of randomized clinical trials using Bayesian approach as sensitivity analyses[J].Am J Gastroenterol, 2007, 102 (8) :1799-1807.
    [29]CARBONE M, MELLS GF, PELLS G, et al.Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid[J].Gastroenterology, 2013, 144 (3) :560-569.
    [30]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.
    [31]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.
    [32]TANAKA A, HIROHARA J, NAKANUMA Y, et al.Biochemical responses to bezafibrate improve long-term outcome in asymptomatic patients with primary biliary cirrhosis refractory to UDCA[J].J Gastroenterol, 2015, 50 (6) :675-682.
    [33]HOSONUMA K, SATO K, YAMAZAKI Y, et al.A prospective randomized controlled study of long-term combination therapy using ursodeoxycholic acid and bezafibrate in patients with primary biliary cirrhosis and dyslipidemia[J].Am J Gastroenterol, 2015, 110 (3) :423-431.
    [34]HAZZAN R, TUR-KASPA R.Bezafibrate treatment of primary biliary cirrhosis following incomplete response to ursodeoxycholic acid[J].J Clin Gastroenterol, 2010, 44 (5) :371-373.
    [35]RUDIC JS, POROPAT G, KRSTIC MN, et al.Bezafibrate for primary biliary cirrhosis[J].Cochrane Database Syst Rev, 2012, 1:CD009145.
    [36]WALKER LJ, NEWTON J, JONES DE, et al.Comment on biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis[J].Hepatology, 2009, 49 (1) :337-338.
    [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]GONG Y, GLUUD C.Colchicine for primary biliary cirrhosis:a Cochrane Hepato-Biliary Group systematic review of randomized clinical trials[J].Am J Gastroenterol, 2005, 100 (8) :1876-1885.
    [39]MYERS RP, SWAIN MG, LEE SS, et al.B-cell depletion with rituximab in patients with primary biliary cirrhosis refractory to ursodeoxycholic acid[J].Am J Gastroenterol, 2013, 108 (6) :933-941.
    [40]MOUSA HS, CARBONE M, MALINVERNO F, et al.Novel therapeutics for primary biliary cholangitis:toward a disease-stagebased approach[J].Autoimmun Rev, 2016, 15 (9) :870-876.
    [41]ADAM R, KARAM V, DELVART V, et al.Evolution of indications and results of liver transplantation in Europe.A report from the European Liver Transplant Registry (ELTR) [J].J Hepatol, 2012, 57 (3) :675-688.
    [42]BOSCH A, DUMORTIER J, MAUCORT-BOULCH D, et al.Preventive administration of UDCA after liver transplantation for primary biliary cirrhosis is associated with a lower risk of disease recurrence[J].J Hepatol, 2015, 63 (6) :1449-1458.
  • 加载中
计量
  • 文章访问数:  1677
  • HTML全文浏览量:  37
  • PDF下载量:  391
  • 被引次数: 0
出版历程
  • 收稿日期:  2017-02-21
  • 出版日期:  2017-08-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回