Influencing factors for suboptimal response to ursodeoxycholic acid in primary biliary cholangitis and related advances in treatment

Xinyue Wu; Wenjun Du

doi:10.12449/JCH260929

Volume 42 Issue 9

Sep. 2026

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Article Navigation > Journal of Clinical Hepatology > 2026 > 42(9): 2217-2223

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Influencing factors for suboptimal response to ursodeoxycholic acid in primary biliary cholangitis and related advances in treatment

DOI: 10.12449/JCH260929

Xinyue Wu,
Wenjun Du^{,
,}

Division of Liver Disease Center，Public Health Clinical Center Affiliated to Shandong University，Jinan 250101，China

Research funding:

Shandong Provincial Natural Science Foundation (ZR2023MH143)

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Corresponding author: Du Wenjun， crbdwj@126.com （ORCID： 0000-0002-6753-5910）
Received Date: 2026-01-07
Accepted Date: 2026-03-05
Published Date: 2026-09-25

Abstract

Abstract

Primary biliary cholangitis （PBC） is an autoimmune-mediated chronic cholestatic liver disease. Ursodeoxycholic acid （UDCA） is the first-line treatment drug for PBC， yet some patients with suboptimal biochemical response to UDCA face a significant increase in the risk of disease progression and often have a poor prognosis. This article systematically summarizes the currently established criteria for biochemical response and analyzes the factors and underlying mechanisms associated with suboptimal UDCA response from multiple perspectives including genetic background， demographic factors， immunological features， and the gut-liver axis. Furthermore， it outlines the available second-line treatment drugs and emerging therapies， in order to provide a basis for early identification of high-risk patients and optimization of treatment strategies， as well as a reference for future research directions.
- Liver Cirrhosis， Biliary,
- Ursodeoxycholic Acid,
- Treatment Outcome,
- Root Cause Analysis

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References(44)

References

[1]	Trivella J, John B V, Levy C. Primary biliary cholangitis: Epidemiology, prognosis, and treatment[J]. Hepatol Commun, 2023, 7( 6): e0179. DOI: 10.1097/HC9.0000000000000179.
[2]	Harms M H, van Buuren H R, Corpechot C, et al. Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis[J]. J Hepatol, 2019, 71( 2): 357- 365. DOI: 10.1016/j.jhep.2019.04.001.
[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. DOI: 10.1016/j.jhep.2017.03.022.
[4]	Han W J, Song T, Huang Z Y, et al. Distinct signatures of gut microbiota and metabolites in primary biliary cholangitis with poor biochemical response after ursodeoxycholic acid treatment[J]. Cell Biosci, 2024, 14( 1): 80. DOI: 10.1186/s13578-024-01253-1.
[5]	Lammers W J, Hirschfield G M, 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. DOI: 10.1053/j.gastro.2015.07.061.
[6]	Carbone M, Sharp S J, 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. DOI: 10.1002/hep.28017.
[7]	Marenco-Flores A, Rojas Amaris N, Kahan T, et al. The external validation of GLOBE and UK-PBC risk scores for predicting ursodeoxycholic acid treatment response in a large U.S. cohort of primary biliary cholangitis patients[J]. J Clin Med, 2024, 13( 15): 4497. DOI: 10.3390/jcm13154497.
[8]	Wang H X, Li Y, Pu X T, et al. MGAT5/TMEM163 variant is associated with prognosis in ursodeoxycholic acid-treated patients with primary biliary cholangitis[J]. J Gastroenterol, 2024, 59( 1): 66- 74. DOI: 10.1007/s00535-023-02045-z.
[9]	Sanchez V B, Ali S, Escobar A, et al. Transmembrane 163(TMEM163) protein effluxes zinc[J]. Arch Biochem Biophys, 2019, 677: 108166. DOI: 10.1016/j.abb.2019.108166.
[10]	Salm E J, Dunn P J, Shan L L, et al. TMEM163 regulates ATP-gated P2X receptor and behavior[J]. Cell Rep, 2020, 31( 9): 107704. DOI: 10.1016/j.celrep.2020.107704.
[11]	Chen R R, Li Y J, Zhou X M, et al. The association between bile salt export pump single-nucleotide polymorphisms and primary biliary cirrhosis susceptibility and ursodeoxycholic acid response[J]. Dis Markers, 2014, 2014: 350690. DOI: 10.1155/2014/350690.
[12]	Jiang Ting. Activation of the CCL5/CCR5 axis by omega-6 fatty acids promotes the progression of primary biliary cholangitis[D]. Kunming: Kunming Medical University, 2022. DOI: 10.27202/d.cnki.gkmyc.2022.000951. 江婷. ω-6脂肪酸激活CCL5/CCR5轴促进原发性胆汁性胆管炎进展的机制研究[D]. 昆明: 昆明医科大学, 2022. DOI: 10.27202/d.cnki.gkmyc.2022.000951.
[13]	Li Lin, Song Yi, Chen Xinyu, et al. Bioinformatic analysis of differentially expressed genes and immune cell infiltration in primary biliary cholangitis patients with poor response to ursodeoxycholic acid therapy[J]. Chin J Cell Mol Immunol, 2022, 38( 1): 16- 23. DOI: 10.13423/j.cnki.cjcmi.009282. 李麟, 宋翊, 陈新瑜, 等. 原发性胆汁性胆管炎熊去氧胆酸治疗应答不佳的差异基因及免疫细胞浸润生物信息学分析[J]. 细胞与分子免疫学杂志, 2022, 38( 1): 16- 23. DOI: 10.13423/j.cnki.cjcmi.009282.
[14]	Gao Lili, Zhang Yijin, Gao Xuesong, et al. Analysis of differential expression of lncRNA and mRNA in liver tissue of female primary biliary cholangitis patients with poor response to ursodeoxycholic acid[J/OL]. Chin J Liver Dis Electron Version, 2023, 15( 2): 47- 53. DOI: 10.3969/j.issn.1674-7380.2023.02.008. 高丽丽, 张亦瑾, 高学松, 等. 熊去氧胆酸应答不佳原发性胆汁性胆管炎女性患者肝组织lncRNA、mRNA差异表达分析[J/OL]. 中国肝脏病杂志(电子版), 2023, 15( 2): 47- 53. DOI: 10.3969/j.issn.1674-7380.2023.02.008.
[15]	Zhang F X, Luan J H, Suo L J, et al. Altered gut microbiota and metabolite profiles in community-acquired pneumonia: A metagenomic and metabolomic study[J]. Microbiol Spectr, 2025, 13( 4): e0263924. DOI: 10.1128/spectrum.02639-24.
[16]	Mohanty I, Mannochio-Russo H, Schweer J V, et al. The underappreciated diversity of bile acid modifications[J]. Cell, 2024, 187( 7): 1801- 1818. DOI: 10.1016/j.cell.2024.02.019.
[17]	Li T G, Hasan M N, Gu L J. Bile acids regulation of cellular stress responses in liver physiology and diseases[J]. eGastroenterology, 2024, 2( 2): e100074. DOI: 10.1136/egastro-2024-100074.
[18]	Chen W H, Wei Y R, Xiong A Z, et al. Comprehensive analysis of serum and fecal bile acid profiles and interaction with gut microbiota in primary biliary cholangitis[J]. Clin Rev Allergy Immunol, 2020, 58( 1): 25- 38. DOI: 10.1007/s12016-019-08731-2.
[19]	He T Y, Wang Y, Zhao L, et al. Integrated microbiota-bile acid analysis as potential NonInvasive biomarkers for ulcerative colitis staging diagnose[J]. FASEB J, 2025, 39( 15): e70859. DOI: 10.1096/fj.202501078R.
[20]	Martinez-Gili L, Pechlivanis A, McDonald J A K, et al. Bacterial and metabolic phenotypes associated with inadequate response to ursodeoxycholic acid treatment in primary biliary cholangitis[J]. Gut Microbes, 2023, 15( 1): 2208501. DOI: 10.1080/19490976.2023.2208501.
[21]	Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D, et al. The challenges of primary biliary cholangitis: What is new and what needs to be done[J]. J Autoimmun, 2019, 105: 102328. DOI: 10.1016/j.jaut.2019.102328.
[22]	Wu Y H, Chiu Y L, Lin J C, et al. New insights into sex differences in primary biliary cholangitis. Gender difference in primary biliary cholangitis[J]. J Pak Med Assoc, 2022, 72( 5): 896- 900. DOI: 10.47391/JPMA.01124.
[23]	Haij K, El Azzam N, Goujdami N, et al. Primary biliary cholangitis in men: A case report[J]. SAS J Med, 2024, 10( 9): 930- 933. DOI: 10.36347/sasjm.2024.v10i09.022.
[24]	Cheung A C, Lammers W J, Murillo Perez C F, et al. Effects of age and sex of response to ursodeoxycholic acid and transplant-free survival in patients with primary biliary cholangitis[J]. Clin Gastroenterol Hepatol, 2019, 17( 10): 2076- 2084. DOI: 10.1016/j.cgh.2018.12.028.
[25]	John B V, Khakoo N S, Schwartz K B, et al. Ursodeoxycholic acid response is associated with reduced mortality in primary biliary cholangitis with compensated cirrhosis[J]. Am J Gastroenterol, 2021, 116( 9): 1913- 1923. DOI: 10.14309/ajg.0000000000001280.
[26]	Song Zhaoyi, Wang Jingjing, Shi Qingyun. Regulation of estrogen receptor α on bile acid transporters related gene and its correlation with intrahepatic cholestasis in pregnant rats[J]. Chin J Fam Plan Gynecotokology, 2016, 8( 10): 56- 58, 62. DOI: 10.3969/j.issn.1674-4020.2016.10.16. 宋昭逸, 王晶晶, 时青云. 雌激素受体α对胆汁酸转运相关基因的调控及其与孕鼠肝内胆汁淤积症发生的相关性[J]. 中国计划生育和妇产科, 2016, 8( 10): 56- 58, 62. DOI: 10.3969/j.issn.1674-4020.2016.10.16.
[27]	Carbone M, Mells G F, 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. DOI: 10.1053/j.gastro.2012.12.005.
[28]	Yehezkel E, Israel I, Houri I, et al. Real-world management of patients with primary biliary cholangitis-a retrospective study from a tertiary medical center in Israel[J]. J Clin Med, 2021, 10( 19): 4551. DOI: 10.3390/jcm10194551.
[29]	Barron-Millar B, Ogle L, Mells G, et al. The serum proteome and ursodeoxycholic acid response in primary biliary cholangitis[J]. Hepatology, 2021, 74( 6): 3269- 3283. DOI: 10.1002/hep.32011.
[30]	Wang C, Qin Z Y, Zhang M M, et al. Autoantibodes to GP210 are a metric for UDCA responses in primary biliary cholangitis[J]. J Transl Autoimmun, 2024, 8: 100239. DOI: 10.1016/j.jtauto.2024.100239.
[31]	Ma Di, Tai Wenlin. The role and impact of macrophages in the pathogenesis of primary biliary cholangitis[J]. J Clin Hepatol, 2024, 40( 1): 157- 160. DOI: 10.12449/JCH240126. 马狄, 邰文琳. 巨噬细胞在原发性胆汁性胆管炎发病中的作用机制及影响[J]. 临床肝胆病杂志, 2024, 40( 1): 157- 160. DOI: 10.12449/JCH240126.
[32]	Mulcahy V, Liaskou E, Martin J E, et al. Regulation of immune responses in primary biliary cholangitis: A transcriptomic analysis of peripheral immune cells[J]. Hepatol Commun, 2023, 7( 4): e0110. DOI: 10.1097/HC9.0000000000000110.
[33]	Wang Z L, Liu Z C, Zheng J R, et al. The effects of low-dose IL-2 on Th17/Treg cell imbalance in primary biliary cholangitis mouse models[J]. BMC Gastroenterol, 2024, 24( 1): 87. DOI: 10.1186/s12876-024-03176-0.
[34]	Wang L F, Sun Y, Zhang Z, et al. CXCR5⁺CD4⁺ T follicular helper cells participate in the pathogenesis of primary biliary cirrhosis[J]. Hepatology, 2015, 61( 2): 627- 638. DOI: 10.1002/hep.27306.
[35]	Nevens F, Trauner M, Manns M P. Primary biliary cholangitis as a roadmap for the development of novel treatments for cholestatic liver diseases[J]. J Hepatol, 2023, 78( 2): 430- 441. DOI: 10.1016/j.jhep.2022.10.007.
[36]	Yang Y S, He X S, Rojas M, et al. Mechanism-based target therapy in primary biliary cholangitis: Opportunities before liver cirrhosis?[J]. Front Immunol, 2023, 14: 1184252. DOI: 10.3389/fimmu.2023.1184252.
[37]	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.
[38]	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[J]. JHEP Rep, 2022, 4( 11): 100544. DOI: 10.1016/j.jhepr.2022.100544.
[39]	Floreani A. Experimental pharmacological agents for the treatment of primary biliary cholangitis[J]. J Exp Pharmacol, 2020, 12: 643- 652. DOI: 10.2147/JEP.S267375.
[40]	Trauner M, Levy C, Tanaka A, et al. Cilofexor in non-cirrhotic primary sclerosing cholangitis(PRIMIS): A randomised, double-blind, multicentre, placebo-controlled, phase 3 trial[J]. Lancet Gastroenterol Hepatol, 2026, 11( 1): 46- 58. DOI: 10.1016/S2468-1253(25)00208-0.
[41]	Kowdley K V, Bonder A, Heneghan M A, et al. Final data of the phase 2a intrepid study with EDP-305, a non-bile acid farnesoid X receptor(FXR) agonist[J]. Hepatology, 2020, 72( 1 Suppl): 746A- 747A. DOI: 10.1002/hep.31579.
[42]	Hirschfield G M, Bowlus C L, Mayo M J, et al. A phase 3 trial of seladelpar in primary biliary cholangitis[J]. N Engl J Med, 2024, 390( 9): 783- 794. DOI: 10.1056/NEJMoa2312100.
[43]	Kowdley K V, Bowlus C L, Levy C, et al. Efficacy and safety of elafibranor in primary biliary cholangitis[J]. N Engl J Med, 2024, 390( 9): 795- 805. DOI: 10.1056/NEJMoa2306185.
[44]	Zhang Zishan, Zhang Yaowu, Dong Xiaoming, et al. Study on the efficacy of alfacalcidol combined with ursodeoxycholic acid in primary biliary cholangitis[J]. Chin J Clin Pharmacol Ther, 2024, 29( 10): 1161- 1167. DOI: 10.12092/j.issn.1009-2501.2024.10.009. 张梓珊, 张耀武, 董晓明, 等. 阿法骨化醇联合熊去氧胆酸对原发性胆汁性胆管炎的疗效研究[J]. 中国临床药理学与治疗学, 2024, 29( 10): 1161- 1167. DOI: 10.12092/j.issn.1009-2501.2024.10.009.

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Influencing factors for suboptimal response to ursodeoxycholic acid in primary biliary cholangitis and related advances in treatment

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Influencing factors for suboptimal response to ursodeoxycholic acid in primary biliary cholangitis and related advances in treatment

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