难治性原发性胆汁性胆管炎研究进展*

doi:10.3969/j.issn.1672-5069.2025.01.040

摘要/Abstract

摘要： 原发性胆汁性胆管炎(PBC),也称原发性胆汁性肝硬化,是一种慢性自身免疫性肝内胆汁淤积性疾病。熊去氧胆酸(UDCA)是目前治疗PBC的一线药物,可改善生化学指标,延缓疾病进程。但仍有30～40%患者对UDCA应答差,此类患者被称为难治性PBC,其肝硬化及相关并发症的发生率较高。针对该类患者的早期预警、治疗和预后评估仍是目前一大难题。本文主要综述了难治性PBC的临床特征、影响因素、治疗药物和预后相关的研究进展,以期提高临床医师对难治性PBC的认识。

关键词: PBC, 熊去氧胆酸, 不应答, 影响因素, 治疗, 预后

Abstract: Primary biliary cholangitis (PBC), also known as primary biliary cirrhosis, is a chronic intrahepatic autoimmune cholestatic disease. Ursodeoxycholic acid (UDCA) is first line of treatment for PBC, which can improve biochemical indicators and slow down disease progress, while 30% to 40% of patients with PBC still have poor response to UDCA therapy, which is called refractory PBC. These patients have a higher incidence of cirrhosis and related complications, and early warning, institution treatment and prognosis evaluation for these patients remain a major challenge. The aim of this review is to present the latest research on the clinical features, influencing factors, therapeutic medicines and prognosis of patients with refractory PBC.

Key words: Primary biliary cholangitis, Ursodeoxycholic acid, Poor response, Influencing factors, Treatment, Prognosis

杨爽, 高学松, 段雪飞. 难治性原发性胆汁性胆管炎研究进展^*[J]. 实用肝脏病杂志, 2025, 28(1): 156-159.

Yang Shuang, Gao Xuesong, Duan Xuefei. Refractory primary biliary cholangitis:current landscape and perspective[J]. Journal of Practical Hepatology, 2025, 28(1): 156-159.

参考文献

[1] Goel A,Kim WR.Natural history of primary biliary cholangitis in the ursodeoxycholic acid era:role of scoring systems.Clin Liver Dis,2018,22(3):563-578.
[2] Yang C,Guo G,Li B,et al.Prediction and evaluation of high-risk patients with primary biliary cholangitis receiving ursodeoxycholic acid therapy:an early criterion.Hepatol Int,2023,17(1):237-248.
[3] 刘会敏,张洪文,林睿,等.难治型原发性胆管炎性胆管炎患者临床特点分析.世界华人消化杂志,2019,27(4): 238-244.
[4] 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.Gastroenterology,2013,144(3):560-569.
[5] 刘一锋,凡小丽,沈怡,等.PBC治疗应答的影响因素及预后预测作用研究.四川大学学报(医学版),2023,54(5):930-936.
[6] Guo GY,Shi YQ,Wang L,et al.Serum vitamin D level is associated with disease severity and response to ursodeoxycholic acid in primary biliary cirrhosis.Aliment Pharmacol Ther,2015,42(2):221-230.
[7] Barron-Millar B,Ogle L,Mells G,et al.The serum proteome and ursodeoxycholic acid response in primary biliary cholangitis.Hepatology,2021,74(6):3269-3283.
[8] 张晓倩,杨慧,孟蝶,等.PBC患者血清核因子相关因子2、血红素加氧酶1的含量与熊去氧胆酸短期应答的相关性.中华临床医师杂志(电子版),2020,14(5):364-369.
[9] 李麟,宋翊,陈新瑜,等.PBC熊去氧胆酸治疗不应答的差异基因及免疫细胞浸润生物信息学分析.细胞与分子免疫学杂志.2022,38(1):16-23.
[10] 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 Hepatol,1999,30(5):830-835.
[11] 黄桂芳,杨晋辉.自身抗体与熊去氧胆酸治疗PBC生化应答的关系探讨.解放军医学杂志,2022,47(02):143-149.
[12] 张骏飞,许何明,宋海燕,等.自身免疫性肝炎-PBC重叠综合征:巴黎标准诊断中国患者灵敏度低,实用肝脏病杂志,2019,22(4):537-540.
[13] Trauner M,Nevens F,Shiffman ML,et al.Long-term efficacy and safety of obeticholic acid for patients with primary biliary cholangitis:3-year results of an international open-label extension study.Lancet Gastroenterol Hepatol,2019,4(6):445-453.
[14] Kowdley KV,Luketic V,Chapman R,et al.A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis.Hepatology,2018,67(5):1890-1902.
[15] Trauner M,Nevens F,Shiffman ML,et al.Long-term efficacy and safety of obeticholic acid for patients with primary biliary cholangitis:3-year results of an international open-label extension study.Lancet Gastroenterol Hepatol,2019,4(6):445-453.
[16] Schramm C,Wedemeyer H,Mason A,et al.Farnesoid X receptor agonist tropifexor attenuates cholestasis in a randomised trial in patients with primary biliary cholangitis.JHEP Rep,2022,4(11):100544.
[17] Schwabl P,Hambruch E,Seeland BA,et al.The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction.J Hepatol,2017,66(4):724-733.
[18] 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.Hepatology,2019,70(3):788-801.
[19] Zhang H,Li S,Feng Y,et al.Efficacy of fibrates in the treatment of primary biliary cholangitis:a meta-analysis.Clin Exp Med,2023,23(5):1741-1749.
[20] Liu Y,Guo G,Zheng L,et al.Effectiveness of fenofibrate in treatment-naive patients with primary biliary cholangitis:a randomized clinical trial.Am J Gastroenterol,2023,118(11):1973-1979.
[21] Schattenberg JM,Pares A,Kowdley KV,et al.A randomized placebo-controlled trial of elafibranor in patients with primary biliary cholangitis and incomplete response to UDCA.J Hepatol,2021,74(6):1344-1354.
[22] Hirschfield GM,Shiffman ML,Gulamhusein A,et al.Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: enhance, a phase 3,randomized,placebo-controlled study.Hepatology,2023,78(2):397-415.
[23] Soret PA,Lam L,Carrat F,et al.Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult-to-treat primary biliary cholangitis.Aliment Pharmacol Ther,2021,53(10):1138-1146.
[24] Hirschfield GM,Beuers U,Kupcinskas L,et al.A placebo-controlled randomised trial of budesonide for PBC following an insufficient response to UDCA.J Hepatol,2021,74(2):321-329.
[25] 何学元,马建勋,杨屹立,等.布地奈德治疗熊去氧胆酸治疗不应答的PBC患者疗效及血清氧化应激指标的变化.实用肝脏病杂志,2023,26(3):376-379.
[26] Invernizzi P,Carbone M,Jones D,et al.Setanaxib, a first-in-class selective NADPH oxidase 1/4 inhibitor for primary biliary cholangitis:A randomized, placebo-controlled, phase 2 trial.Liver Int,2023,43(7):1507-1522.

难治性原发性胆汁性胆管炎研究进展^*

Refractory primary biliary cholangitis:current landscape and perspective

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