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

原发性硬化性胆管炎药物治疗进展

盛夏 纪庆明 李昕宇 王丽宏 牛俊奇

引用本文:
Citation:

原发性硬化性胆管炎药物治疗进展

DOI: 10.12449/JCH240526
基金项目: 

国家自然科学基金 (82200666)

利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:盛夏负责文献检索,撰写论文;纪庆明负责资料分析;李昕宇、王丽宏、牛俊奇负责指导及最终定稿。
详细信息
    通信作者:

    李昕宇, xinyuli@jlu.edu.cn (ORCID: 0000-0001-6215-4708)

    王丽宏, whlhebykdx@163.com (ORCID: 0009-0009-6263-0028)

    牛俊奇, junqiniu@jlu.edu.cn (ORCID: 0000-0001-5415-2024)

Advances in drug therapy for primary sclerosing cholangitis

Research funding: 

National Natural Science Foundation of China (82200666)

More Information
  • 摘要: 原发性硬化性胆管炎(PSC)是一种以慢性进行性胆管炎症为特征的胆汁淤积性疾病,在我国发病率低,预后差,尚无药物治疗能改变PSC的进程,肝移植是唯一有效治疗手段,移植后5年生存率可达85%。基于PSC现状,药物治疗面临巨大挑战。目前治疗PSC的药物尚处于临床试验阶段,初步显示出应用前景,其中熊去氧胆酸是研究最广泛、最常用的药物。除此之外,还有很多新兴药物正在研究中。本文将围绕PSC最新药物治疗进展进行概述。

     

  • [1] European Association for the Study of the Liver. EASL Clinical Practice Guidelines on sclerosing cholangitis[J]. J Hepatol, 2022, 77( 3): 761- 806. DOI: 10.1016/j.jhep.2022.05.011.
    [2] LILLEMOE KD, PITT HA, CAMERON JL. Primary sclerosing cholangitis[J]. Surg Clin N Am, 1990, 70( 6): 1381- 1402. DOI: 10.1016/s0039-6109(16)45290-4.
    [3] LINDOR KD. Ursodiol for primary sclerosing cholangitis. mayo primary sclerosing cholangitis-ursodeoxycholic acid study group[J]. N Engl J Med, 1997, 336( 10): 691- 695. DOI: 10.1056/NEJM199703063361003.
    [4] OLSSON R, BOBERG KM, de MUCKADELL OS, et al. High-dose ursodeoxycholic acid in primary sclerosing cholangitis: A 5-year multicenter, randomized, controlled study[J]. Gastroenterology, 2005, 129( 5): 1464- 1472. DOI: 10.1053/j.gastro.2005.08.017.
    [5] LINDOR KD, KOWDLEY KV, LUKETIC VAC, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis[J]. Hepatology, 2009, 50( 3): 808- 814. DOI: 10.1002/hep.23082.
    [6] EATON JE, SILVEIRA MG, PARDI DS, et al. High-dose ursodeoxycholic acid is associated with the development of colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis[J]. Am J Gastroenterol, 2011, 106( 9): 1638- 1645. DOI: 10.1038/ajg.2011.156.
    [7] TRIANTOS CK, KOUKIAS NM, NIKOLOPOULOU VN, et al. Meta-analysis: Ursodeoxycholic acid for primary sclerosing cholangitis[J]. Aliment Pharmacol Ther, 2011, 34( 8): 901- 910. DOI: 10.1111/j.1365-2036.2011.04822.x.
    [8] TRAUNER M, FUCHS CD, HALILBASIC E, et al. New therapeutic concepts in bile acid transport and signaling for management of cholestasis[J]. Hepatology, 2017, 65( 4): 1393- 1404. DOI: 10.1002/hep.28991.
    [9] FICKERT P, WAGNER M, MARSCHALL HU, et al. 24-norUrsodeoxycholic acid is superior to ursodeoxycholic acid in the treatment of sclerosing cholangitis in Mdr2(Abcb4) knockout mice[J]. Gastroenterology, 2006, 130( 2): 465- 481. DOI: 10.1053/j.gastro.2005.10.018.
    [10] FICKERT P, HIRSCHFIELD GM, DENK G, et al. norUrsodeoxycholic acid improves cholestasis in primary sclerosing cholangitis[J]. J Hepatol, 2017, 67( 3): 549- 558. DOI: 10.1016/j.jhep.2017.05.009.
    [11] KOWDLEY KV, VUPPALANCHI R, LEVY C, et al. A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis[J]. J Hepatol, 2020, 73( 1): 94- 101. DOI: 10.1016/j.jhep.2020.02.033.
    [12] TRAUNER M, GULAMHUSEIN A, HAMEED B, et al. The nonsteroidal farnesoid X receptor agonist cilofexor(GS-9674) improves markers of cholestasis and liver injury in patients with primary sclerosing cholangitis[J]. Hepatology, 2019, 70( 3): 788- 801. DOI: 10.1002/hep.30509.
    [13] LOOMBA R, NOUREDDI M, KOWDLEY KV, et al. Combination therapies including cilofexor and firsocostat for bridging fibrosis and cirrhosis attributable to NASH[J]. Hepatology, 2021, 73( 2): 625- 643. DOI: 10.1002/hep.31622.
    [14] SANYAL AJ, LING L, BEUERS U, et al. Potent suppression of hydrophobic bile acids by aldafermin, an FGF19 analogue, across metabolic and cholestatic liver diseases[J]. JHEP Rep, 2021, 3( 3): 100255. DOI: 10.1016/j.jhepr.2021.100255.
    [15] HIRSCHFIELD GM, CHAZOUILLÈRES O, DRENTH JP, et al. Effect of NGM282, an FGF19 analogue, in primary sclerosing cholangitis: A multicenter, randomized, double-blind, placebo-controlled phase II trial[J]. J Hepatol, 2019, 70( 3): 483- 493. DOI: 10.1016/j.jhep.2018.10.035.
    [16] ASSIS DN, ABDELGHANY O, CAI SY, et al. Combination therapy of all-trans retinoic acid with ursodeoxycholic acid in patients with primary sclerosing cholangitis: A human pilot study[J]. J Clin Gastroenterol, 2017, 51( 2): e11- e16. DOI: 10.1097/MCG.0000000000000591.
    [17] MIZUNO S, HIRANO K, TADA M, et al. Bezafibrate for the treatment of primary sclerosing cholangitis[J]. J Gastroenterol, 2010, 45( 7): 758- 762. DOI: 10.1007/s00535-010-0204-x.
    [18] LEMOINNE S, PARES A, REIG A, et al. Primary sclerosing cholangitis response to the combination of fibrates with ursodeoxycholic acid: French-Spanish experience[J]. Clin Res Hepatol Gastroenterol, 2018, 42( 6): 521- 528. DOI: 10.1016/j.clinre.2018.06.009.
    [19] HATAMI B, MOSALA M, HASSANI AH, et al. Fenofibrate in primary sclerosing cholangitis; a randomized, double-blind, placebo-controlled trial[J]. Pharmacol Res Perspect, 2022, 10( 4): e00984. DOI: 10.1002/prp2.984.
    [20] van den HOEK AM, VERSCHUREN L, CASPERS MPM, et al. Beneficial effects of elafibranor on NASH in E3L.CETP mice and differences between mice and men[J]. Sci Rep, 2021, 11( 1): 5050. DOI: 10.1038/s41598-021-83974-8.
    [21] HEGADE VS, JONES DEJ, HIRSCHFIELD GM. Apical sodium-dependent transporter inhibitors in primary biliary cholangitis and primary sclerosing cholangitis[J]. Dig Dis, 2017, 35( 3): 267- 274. DOI: 10.1159/000450988.
    [22] BOWLUS CL, EKSTEEN B, CHEUNG AC, et al. Safety, tolerability, and efficacy of maralixibat in adults with primary sclerosing cholangitis: Open-label pilot study[J]. Hepatol Commun, 2023, 7( 6): e0153. DOI: 10.1097/hc9.0000000000000153.
    [23] CABALLERO FJ, RODRIGUES PM, LIZASO AA, et al. A3907, a systemic ASBT inhibitor, improves cholestasis in mice by inhibiting multi-organ bile acid transport and shows translational relevance to human[J]. J Hepatol, 2023, 78: S62. DOI: 10.1016/s0168-8278(23)00528-7.
    [24] FÄRKKILÄ M, KARVONEN AL, NURMI H, et al. Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: A randomized placebo-controlled trial[J]. Hepatology, 2004, 40( 6): 1379- 1386. DOI: 10.1002/hep.20457.
    [25] TABIBIAN JH, WEEDING E, JORGENSEN RA, et al. Randomised clinical trial: Vancomycin or metronidazole in patients with primary sclerosing cholangitis-a pilot study[J]. Aliment Pharmacol Ther, 2013, 37( 6): 604- 612. DOI: 10.1111/apt.12232.
    [26] DAVIES YK, COX KM, ABDULLAH BA, et al. Long-term treatment of primary sclerosing cholangitis in children with oral vancomycin: An immunomodulating antibiotic[J]. J Pediatr Gastroenterol Nutr, 2008, 47( 1): 61- 67. DOI: 10.1097/MPG.0b013e31816fee95.
    [27] WILSON HJ, KHOKHAR F, ENOCH DA, et al. Point-prevalence survey of carbapenemase-producing Enterobacteriaceae and vancomycin-resistant enterococci in adult inpatients in a university teaching hospital in the UK[J]. J Hosp Infect, 2018, 100( 1): 35- 39. DOI: 10.1016/j.jhin.2018.06.024.
    [28] LINDOR KD, KOWDLEY KV, HARRISON ME, et al. ACG clinical guideline: Primary sclerosing cholangitis[J]. Am J Gastroenterol, 2015, 110( 5): 646- 659; quiz660. DOI: 10.1038/ajg.2015.112.
    [29] CAREY EJ, EATON J, CLAYTON M, et al. A pilot study of vidofludimus calcium for treatment of primary sclerosing cholangitis[J]. Hepatol Commun, 2022, 6( 7): 1589- 1597. DOI: 10.1002/hep4.1926.
    [30] LIU X, WANG HL, LIU XY, et al. Efficacy and safety of immune-modulating therapy for primary sclerosing cholangitis: A systematic review and meta-analysis[J]. Pharmacol Ther, 2022, 237: 108163. DOI: 10.1016/j.pharmthera.2022.108163.
    [31] ANGULO P, BATTS KP, JORGENSEN RA, et al. Oral budesonide in the treatment of primary sclerosing cholangitis[J]. Am J Gastroenterology, 2000, 95( 9): 2333- 2337. DOI: 10.1111/j.1572-0241.2000.02323.x.
    [32] LINDOR KD, WIESNER RH, COLWELL LJ, et al. The combination of prednisone and colchicine in patients with primary sclerosing cholangitis[J]. Am J Gastroenterol, 1991, 86( 1): 57- 61.
    [33] EKSTEEN B, BOWLUS CL, MONTANO-LOZA AJ, et al. Efficacy and safety of cenicriviroc in patients with primary sclerosing cholangitis: PERSEUS study[J]. Hepatol Commun, 2020, 5( 3): 478- 490. DOI: 10.1002/hep4.1619.
    [34] SEGAL-SALTO M, BARASHI N, KATAV A, et al. A blocking monoclonal antibody to CCL24 alleviates liver fibrosis and inflammation in experimental models of liver damage[J]. JHEP Rep, 2020, 2( 1): 100064. DOI: 10.1016/j.jhepr.2019.100064.
    [35] BARASHI N, SEGAL M, AHARON A, et al. CCL24 modulates fibrosis development in primary sclerosing cholangitis: Correlation of human serum CCL24 levels with fibrosis markers and data from the Mdr2-/- mouse model[J]. J Hepatol, 2020, 73: S486. DOI: 10.1016/s0168-8278(20)31452-5.
    [36] LOFTUS EV Jr, FEAGAN BG, PANACCIONE R, et al. Long-term safety of vedolizumab for inflammatory bowel disease[J]. Aliment Pharmacol Ther, 2020, 52( 8): 1353- 1365. DOI: 10.1111/apt.16060.
    [37] LYNCH KD, CHAPMAN RW, KESHAV S, et al. Effects of vedolizumab in patients with primary sclerosing cholangitis and inflammatory bowel diseases[J]. Clin Gastroenterol Hepatol, 2020, 18( 1): 179- 187. e 6. DOI: 10.1016/j.cgh.2019.05.013.
    [38] LABORDA TJ, RICCIUTO A, AUMAR M, et al. Vedolizumab therapy in children with primary sclerosing cholangitis: Data from the pediatric primary sclerosing cholangitis consortium[J]. J Pediatr Gastroenterol Nutr, 2020, 71( 4): 459- 464. DOI: 10.1097/MPG.0000000000002855.
    [39] KOWDLEY KV, FORMAN L, EKSTEEN B, et al. A randomized, dose-finding, proof-of-concept study of berberine ursodeoxycholate in patients with primary sclerosing cholangitis[J]. Am J Gastroenterol, 2022, 117( 11): 1805- 1815. DOI: 10.14309/ajg.0000000000001956.
    [40] DECARIS ML, SCHAUB JR, CHEN C, et al. Dual inhibition of αvβ6 and αvβ1 reduces fibrogenesis in lung tissue explants from patients with IPF[J]. Respir Res, 2021, 22( 1): 265. DOI: 10.1186/s12931-021-01863-0.
    [41] LITTLE R, WINE E, KAMATH BM, et al. Gut microbiome in primary sclerosing cholangitis: A review[J]. World J Gastroenterol, 2020, 26( 21): 2768- 2780. DOI: 10.3748/wjg.v26.i21.2768.
  • 加载中
计量
  • 文章访问数:  343
  • HTML全文浏览量:  257
  • PDF下载量:  66
  • 被引次数: 0
出版历程
  • 收稿日期:  2023-08-29
  • 录用日期:  2023-10-30
  • 出版日期:  2024-05-25
  • 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