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

难治性原发性胆汁性胆管炎的治疗新进展

倪萍 凡小丽 文茂瑶 杨丽

引用本文:
Citation:

难治性原发性胆汁性胆管炎的治疗新进展

DOI: 10.3969/j.issn.1001-5256.2017.11.040
基金项目: 

四川省科技厅应用基础项目(2017JY0071); 

详细信息
  • 中图分类号: R575.7

New advances in the treatment of refractory primary biliary cholangitis

Research funding: 

 

  • 摘要: 原发性胆汁性胆管炎(PBC)是一种以小胆管损伤为特点的自身免疫性肝病。熊去氧胆酸(UDCA)是治疗本病的主要药物,但约40%的PBC患者对UDCA生化应答欠佳,预后较差。总结了难治性PBC患者的治疗新选择。2017年,奥贝胆酸已被欧洲肝病学会推荐作为UDCA应答不佳PBC的二线治疗药物。贝特类药物或布地奈德联合UDCA治疗难治性PBC的相关研究也取得了一定进展,但其疗效与安全性仍需大样本随机双盲对照试验进一步验证。单克隆抗体、改变胆汁酸生成或重吸收药物等尚处于实验阶段。目前,肝移植仍然是延长终末期PBC患者生存期的唯一治疗方法。

     

  • [1]TANAKA A, TAKIKAWA H, MOCHIDA S, et al.Changing nomenclature for PBC from“primary biliary cirrhosis”to“primary biliary cholangitis”[J].J Gastroenterol, 2016, 51 (7) :748-749.
    [2]CAREY EJ, ALI AH, LINDOR KD.Primary biliary cirrhosis[J].The Lancet, 2015, 386 (10003) :1565-1575.
    [3]European Association for the Study of the Liver.EASL Clinical Practice Guidelines:the diagnosis and management of patients with primary biliary cholangitis[J].J Hepatol, 2017, 67 (1) :145-172.
    [4]GRIFFITHS L, DYSON JK, JONES DEJ.The new epidemiology of primary biliary cirrhosis[J].Semin Liver Dis, 2014, 34 (3) :318-328.
    [5]LLEO A, JEPSEN P, MORENGHI E, et al.Evolving trends in female to male incidence and male mortality of primary biliary cholangitis[J].Sci Rep, 2016, 6:25906.
    [6]JONES DE.Pathogenesis of primary biliary cirrhosis[J].Postgrad Med J, 2008, 84 (987) :23-33.
    [7]European Association for the Study of the Liver.EASL Clinical Practice Guidelines:management of cholestatic liver diseases[J].JHepatol, 2009, 51 (2) :237-267.
    [8]TERBORG PC, SCHALM SW, HANSEN BE, et al.Prognosis of ursodeoxycholic acid-treated patients with primary biliary cirrhosis.Results of a 10-year cohort study involving 297 patients[J].Am J Gastroenterol, 2006, 101 (9) :2044-2050.
    [9]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.
    [10]DUAN WJ, TIAN QJ, YOU H, et al.Research advances in primary biliary cholangitis[J].J Clin Hepatol, 2016, 32 (11) :2062-2065. (in Chinese) 段维佳, 田秋菊, 尤红, 等.原发性胆汁性胆管炎的研究进展[J].临床肝胆病杂志, 2016, 32 (11) :2062-2065.
    [11]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.e7.
    [12]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.
    [13]CARBONE M, SHARP SJ, FLACK S, et al.The UK-PBC risk scores:derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cholangitis[J].Hepatology, 2016, 63 (3) :930-950.
    [14]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.e4.
    [15]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.
    [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]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]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.
    [19]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.
    [20]ZHANG LN, SHI TY, SHI XH, et al.Early biochemical response to ursodeoxycholic acid and long-term prognosis of primary biliary cirrhosis:results of a 14-year cohort study[J].Hepatology, 2013, 58 (1) :264-272.
    [21]LINDOR KD.Farnesoid X receptor agonists for primary biliary cirrhosis[J].Curr Opin Gastroenterol, 2011, 27 (3) :285-288.
    [22]ZHAO J, LI W, YAO DK.Role of farnesoid X receptor in treatment of primary biliary cholangitis[J].Chin J Gastroenterol, 2017, 22 (2) :109-111. (in Chinese) 赵健, 李伟, 姚定康.法尼醇X受体在原发性胆汁性胆管炎治疗中的作用[J].胃肠病学, 2017, 22 (2) :109-111.
    [23]FIORUCCI S, ANTONELLI E, RIZZO G, et al.The nuclear receptor SHP mediates inhibition of hepatic stellate cells by FXR and protects against liver fibrosis[J].Gastroenterology, 2004, 127 (5) :1497-1512.
    [24]VERBEKE L, FARRE R, TREBICKA J, et al.Obeticholic acid, a farnesoid X receptor agonist, improves portal hypertension by two distinct pathways in cirrhotic rats[J].Hepatology, 2014, 59 (6) :2286-2298.
    [25]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.
    [26]KOWDLEY KV, JONES D, LUKETIC V, et al.An international study evaluating the farnesoid X receptor agonist obeticholic acid as monotherapy in PBC[J].J Hepatol, 2011, 54 (9) :s13.
    [27]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.
    [28]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].JGastroenterol, 2015, 50 (6) :675-682.
    [29]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.
    [30]WU LH, HAN Y.Application and role of fibrates in treatment of primary biliary cholangitis and related mechanisms[J].J Clin Hepatol, 2016, 32 (12) :2403-2406. (in Chinese) 武李红, 韩英.贝特类药物在原发性胆汁性胆管炎中的应用及作用机制.[J].临床肝胆病杂志, 2016, 32 (12) :2403-2406.
    [31]LENS S, LEOZ M, NAZAL L, et al.Bezafibrate normalizes alkaline phosphatase in primary biliary cirrhosis patients with incomplete response to ursodeoxycholic acid[J].Liver Int, 2014, 34 (2) :197-203.
    [32]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.
    [33]GRIGORIAN AY, MARDINI HE, CORPECHOT C, et al.Fenofibrate is effective adjunctive therapy in the treatment of primary biliary cirrhosis:a meta-analysis[J].Clin Res Hepatol Gastroenterol, 2015, 39 (3) :296-306.
    [34]LEUSCHNER M, GULDUTUNA S, YOU T, et al.Ursodeoxycholic acid and prednisolone versus ursodeoxycholic acid and placebo in the treatment of early stages of primary biliary cirrhosis[J].J Hepatol, 1996, 25 (1) :49-57.
    [35]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.
    [36]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.
    [37]RAUTIAINEN H, KARKKAINEN P, KARVONEN AL, et al.Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis:a three-year randomized trial[J].Hepatology, 2005, 41 (4) :747-752.
    [38]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.
    [39]TSUDA M, MORITOKI Y, LIAN ZX, et al.Biochemical and immunologic effects of rituximab in patients with primary biliary cirrhosis and an incomplete response to ursodeoxycholic acid[J].Hepatology, 2012, 55 (2) :512-521.
    [40]WANG D, ZHANG H, LIANG J, et al.Effect of allogeneic bone marrow-derived mesenchymal stem cells transplantation in a poly I:C-induced primary biliary cirrhosis mouse model[J].Clin Exp Med, 2011, 11 (1) :25-32.
    [41]WANG L, LI J, LIU H, et al.Pilot study of umbilical cord-derived mesenchymal stem cell transfusion in patients with primary biliary cirrhosis[J].J Gastroenterol Hepatol, 2013, 28 (Suppl 1) :85-92.
    [42]WANG L, HAN Q, CHEN H, et al.Allogeneic bone marrow mesenchymal stem cell transplantation in patients with UDCA-resistant primary biliary cirrhosis[J].Stem Cells Dev, 2014, 23 (20) :2482-2489.
    [43]ZHOU M, LEARNED RM, ROSSI SJ, et al.Engineered fibroblast growth factor 19 reduces liver injury and resolves sclerosing cholangitis in Mdr2-deficient mice[J].Hepatology, 2016, 63 (3) :914-929.
    [44]MAYO M, WIGG A, ROBERTS S, et al.NGM282, a novel variant of FGF-19, demonstrates biologic activity in primary biliary cirrhosis patients with an incomplete response to ursodeoxycholic acid:results of a phase 2 multicenter, randomized, double blinded, placebo controlled trial[J].Hepatology, 2015, 62 (10) :263A.
    [45]XU L, SHEN Z, GUO L, et al.Does a betaretrovirus infection trigger primary biliary cirrhosis?[J].Proc Natl Acad Sci U S A, 2003, 100 (14) :8454-8459.
    [46]MASON AL, LINDOR KD, BACON BR, et al.Clinical trial:randomized controlled study of zidovudine and lamivudine for patients with primary biliary cirrhosis stabilized on ursodiol[J].Aliment Pharmacol Ther, 2008, 28 (7) :886-894.
    [47]KAWAMATA Y, FUJII R, HOSOYA M, et al.A G protein-coupled receptor responsive to bile acids[J].J Biol Chem, 2003, 278 (11) :9435-9440.
    [48]WANG YD, CHEN WD, YU D, et al.The G-protein-coupled bile acid receptor, Gpbar1 (TGR5) , negatively regulates hepatic inflammatory response through antagonizing nuclear factor kappa light-chain enhancer of activated B cells (NF-kappa B) in mice[J].Hepatology, 2011, 54 (4) :1421-1432.
  • 加载中
计量
  • 文章访问数:  1758
  • HTML全文浏览量:  52
  • PDF下载量:  436
  • 被引次数: 0
出版历程
  • 收稿日期:  2017-06-26
  • 出版日期:  2017-11-20
  • 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