原发性胆汁性胆管炎的诊治现状与挑战

王璐; 韩英

doi:10.3969/j.issn.1001-5256.2021.10.001

原发性胆汁性胆管炎的诊治现状与挑战

DOI: 10.3969/j.issn.1001-5256.2021.10.001

王璐,
韩英^,

空军军医大学西京医院消化内科，西安 710032

详细信息

通信作者:
韩英，hanying@fmmu.edu.cn

中图分类号: R575.22
计量
- 文章访问数: 1157
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- 被引次数: 0
出版历程
- 收稿日期: 2021-08-22
- 录用日期: 2021-08-22
- 出版日期: 2021-10-20

Diagnosis and treatment of primary biliary cholangitis: Current status and challenges

Lu WANG,
Ying HAN^,

Department of Gastroenterology, Xijing Hospital, Air Force Medical University, Xi'an 710032, China

摘要

摘要: 原发性胆汁性胆管炎是一种女性多发的自身免疫性肝病。主要特征为血清抗线粒体抗体阳性，肝内小胆管进行性、非化脓性、炎症性破坏。目前的认识是遗传和环境的共同作用下，慢性免疫损伤和胆管上皮相互作用的结果。一线治疗药物为熊去氧胆酸。对不耐受或应答不佳者，可以考虑联合二线药物法尼酯X受体激动剂奥贝胆酸，过氧化物酶体增殖物激活受体激动剂贝特类也被视为二线替代药物。患者的基线特征(如年轻、男性和疾病晚期)和血生化指标(特别是胆红素和碱性磷酸酶)被用于疾病风险分层和疗效评估。对瘙痒和乏力等症状的管理也不容忽视。
- 肝硬化, 胆汁性 /
- 诊断 /
- 治疗学
Abstract: Primary biliary cholangitis is an autoimmune liver disease often observed in women, with the main features of positive antimitochondrial antibodies in serum and progressive non-pyogenic inflammatory destruction of small intrahepatic bile ducts. At present, primary biliary cholangitis is considered the result of interaction between chronic immune injury and biliary epithelium under the combined effect of inheritance and environment. Ursodeoxycholic acid is the first-line drug for primary biliary cholangitis; for patients who cannot tolerate ursodeoxycholic acid or have suboptimal response, the second-line drug obeticholic acid, an FXR agonist, can be considered, and the peroxisome proliferator-activated receptor agonists fibrates can be regarded as second-line alternative drugs. Baseline characteristics (such as young age, male sex, and advanced disease) and blood biochemical parameters (especially bilirubin and alkaline phosphatase) are used for disease risk stratification and response evaluation. Management of the symptoms such as pruritus and weakness cannot be ignored.
- Liver Cirrhosis, Biliary /
- Diagnosis /
- Therapeutics

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参考文献(27)

[1]	ADDISON T, GULL W. On a certain affection of the skin-vitiligoidea-α plana, β tuberosa[J]. Guy's Hosp Rep, 1851, 7: 265.
[2]	WANG L, HAN Y. Discussion on the cultivation of scientific research thinking from the research progress of primary biliary cholangitis[J]. Clin Res Prac, 2020, 5(6): 197-198. DOI: 10.19347/j.cnki.2096-1413.202006079. 王璐, 韩英. 从原发性胆汁性胆管炎的研究进展谈科研思维培养[J]. 临床医学研究与实践, 2020, 5(6): 197-198. DOI: 10.19347/j.cnki.2096-1413.202006079.
[3]	AHRENS EH Jr, PAYNE MA, KUNKEL HG, et al. Primary biliary cirrhosis[J]. Medicine (Baltimore), 1950, 29(4): 299-364. DOI: 10.1097/00005792-195012000-00002.
[4]	ASURI S, MCINTOSH S, TAYLOR V, et al. Primary Biliary Cholangitis in British Columbia First Nations: Clinical features and discovery of novel genetic susceptibility loci[J]. Liver Int, 2018, 38(5): 940-948. DOI: 10.1111/liv.13686.
[5]	ZENG N, DUAN W, CHEN S, et al. Epidemiology and clinical course of primary biliary cholangitis in the Asia-Pacific region: A systematic review and meta-analysis[J]. Hepatol Int, 2019, 13(6): 788-799. DOI: 10.1007/s12072-019-09984-x.
[6]	YAGI M, TANAKA A, ABE M, et al. Symptoms and health-related quality of life in Japanese patients with primary biliary cholangitis[J]. Sci Rep, 2018, 8(1): 12542. DOI: 10.1038/s41598-018-31063-8.
[7]	FAN X, WANG T, SHEN Y, et al. Underestimated male prevalence of primary biliary cholangitis in China: Results of a 16-yr cohort study involving 769 patients[J]. Sci Rep, 2017, 7(1): 6560. DOI: 10.1038/s41598-017-06807-7.
[8]	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. DOI: 10.1038/srep25906.
[9]	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, 70(6): 2035-2046. DOI: 10.1002/hep.30552.
[10]	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. DOI: 10.3969/j.issn.1001-5256.2018.11.020. 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. DOI: 10.3969/j.issn.1001-5256.2018.11.020.
[11]	WANG L, SUN K, TIAN A, et al. Fenofibrate improves GLOBE and UK-PBC scores and histological features in primary biliary cholangitis[J]. Minerva Med, 2021. DOI: 10.23736/S0026-4806.21.07316-X.[Online ahead of print]
[12]	EFE C, TAŞÇILAR K, HENRIKSSON I, et al. Validation of risk scoring systems in ursodeoxycholic acid-treated patients with primary biliary cholangitis[J]. Am J Gastroenterol, 2019, 114(7): 1101-1108. DOI: 10.14309/ajg.0000000000000290.
[13]	LLEO A, BOWLUS CL, YANG GX, et al. Biliary apotopes and anti-mitochondrial antibodies activate innate immune responses in primary biliary cirrhosis[J]. Hepatology, 2010, 52(3): 987-998. DOI: 10.1002/hep.23783.
[14]	MONTANO-LOZA AJ, HANSEN BE, CORPECHOT C, et al. Factors associated with recurrence of primary biliary cholangitis after liver transplantation and effects on graft and patient survival[J]. Gastroenterology, 2019, 156(1): 96-107. e1. DOI: 10.1053/j.gastro.2018.10.001.
[15]	SHIMODA S, MIYAKAWA H, NAKAMURA M, et al. CD4 T-cell autoreactivity to the mitochondrial autoantigen PDC-E2 in AMA-negative primary biliary cirrhosis[J]. J Autoimmun, 2008, 31(2): 110-115. DOI: 10.1016/j.jaut.2008.05.003.
[16]	WANG L, WANG J, SHI Y, et al. Identification of a primary biliary cirrhosis associated protein as lysosome-associated membrane protein-2[J]. J Proteomics, 2013, 91: 569-579. DOI: 10.1016/j.jprot.2013.08.019.
[17]	BANALES JM, SÁEZ E, URIZ M, et al. Up-regulation of microRNA 506 leads to decreased Cl^-/HCO3^- anion exchanger 2 expression in biliary epithelium of patients with primary biliary cirrhosis[J]. Hepatology, 2012, 56(2): 687-697. DOI: 10.1002/hep.25691.
[18]	CORDELL HJ, HAN Y, MELLS GF, et al. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways[J]. Nat Commun, 2015, 6: 8019. DOI: 10.1038/ncomms9019.
[19]	GULAMHUSEIN AF, HIRSCHFIELD GM. Primary biliary cholangitis: Pathogenesis and therapeutic opportunities[J]. Nat Rev Gastroenterol Hepatol, 2020, 17(2): 93-110. DOI: 10.1038/s41575-019-0226-7.
[20]	LINDOR KD, BOWLUS CL, BOYER J, et al. Primary biliary cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases[J]. Hepatology, 2019, 69(1): 394-419. DOI: 10.1002/hep.30145.
[21]	POUPON R. Liver alkaline phosphatase: A missing link between choleresis and biliary inflammation[J]. Hepatology, 2015, 61(6): 2080-2090. DOI: 10.1002/hep.27715.
[22]	ALI AH, LINDOR KD. Obeticholic acid for the treatment of primary biliary cholangitis[J]. Expert Opin Pharmacother, 2016, 17(13): 1809-1815. DOI: 10.1080/14656566.2016.1218471.
[23]	NEVENS F, ANDREONE P, MAZZELLA G, et al. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis[J]. N Engl J Med, 2016, 375(7): 631-643. DOI: 10.1056/NEJMoa1509840.
[24]	LEVY C, LINDOR KD. Editorial: Itching to know: Role of fibrates in PBC[J]. Am J Gastroenterol, 2018, 113(1): 56-57. DOI: 10.1038/ajg.2017.432.
[25]	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. DOI: 10.1056/NEJMoa1714519.
[26]	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. DOI: 10.1002/hep.22428.
[27]	SWAIN MG, JONES D. Fatigue in chronic liver disease: New insights and therapeutic approaches[J]. Liver Int, 2019, 39(1): 6-19. DOI: 10.1111/liv.13919.