Cholestatic liver disease and portal hypertension

Li CHEN; Changqing YANG

doi:10.12449/JCH250703

Volume 41 Issue 7

Jul. 2025

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Article Navigation > Journal of Clinical Hepatology > 2025 > 41(7): 1251-1255

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Cholestatic liver disease and portal hypertension

DOI: 10.12449/JCH250703

Li CHEN,
Changqing YANG^{,
,}

Department of Gastroenterology，Tongji Hospital Affiliated to Tongji University，Shanghai 200065，China

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Corresponding author: YANG Changqing， cqyang@tongji.edu.cn （ORCID： 0000-0001-6997-0214）
Received Date: 2025-04-02
Accepted Date: 2025-05-20
Published Date: 2025-07-25

Abstract

Abstract

Cholestatic liver disease （CLD） is a group of rare chronic liver diseases with the core feature of biliary system damage， and the progression of CLD is often complicated by portal hypertension （PH）， which significantly affects the prognosis of patients. This article systematically elaborates on the pathophysiological relationship between CLD and PH， with a focus on the core mechanisms such as bile acid toxicity， fibrosis-driven mechanisms， and vascular remodeling， and it also summarizes the comprehensive management strategy based on evidence-based medicine that integrates etiological treatment and PH intervention. Further studies are needed to analyze the CLD-PH molecular network， develop precise targeted therapies， and promote the application of artificial intelligence in disease stratification and prognosis prediction， so as to improve the clinical outcomes of patients.
- Cholestasis,
- Liver Diseases,
- Hypertension， Portal

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References(45)

References

[1]	European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of cholestatic liver diseases[J]. J Hepatol, 2009, 51( 2): 237- 267. DOI: 10.1016/j.jhep.2009.04.009.
[2]	CHEN HL, WU SH, HSU SH, et al. Jaundice revisited: Recent advances in the diagnosis and treatment of inherited cholestatic liver diseases[J]. J Biomed Sci, 2018, 25( 1): 75. DOI: 10.1186/s12929-018-0475-8.
[3]	MOLINARO A, MARSCHALL HU. Bile acid metabolism and FXR-mediated effects in human cholestatic liver disorders[J]. Biochem Soc Trans, 2022, 50( 1): 361- 373. DOI: 10.1042/BST20210658.
[4]	WILLIAMS R, ALEXANDER G, ARMSTRONG I, et al. Disease burden and costs from excess alcohol consumption, obesity, and viral hepatitis: Fourth report of the Lancet Standing Commission on Liver Disease in the UK[J]. Lancet, 2018, 391( 10125): 1097- 1107. DOI: 10.1016/S0140-6736(17)32866-0.
[5]	KIM WR, LINDOR KD, LOCKE GR 3, et al. Epidemiology and natural history of primary biliary cirrhosis in a US community[J]. Gastroenterology, 2000, 119( 6): 1631- 1636. DOI: 10.1053/gast.2000.20197.
[6]	LV TT, CHEN S, LI M, et al. Regional variation and temporal trend of primary biliary cholangitis epidemiology: A systematic review and meta-analysis[J]. J Gastroenterol Hepatol, 2021, 36( 6): 1423- 1434. DOI: 10.1111/jgh.15329.
[7]	LEVY C, MANNS M, HIRSCHFIELD G. New treatment paradigms in primary biliary cholangitis[J]. Clin Gastroenterol Hepatol, 2023, 21( 8): 2076- 2087. DOI: 10.1016/j.cgh.2023.02.005.
[8]	CAREY EJ, ALI AH, LINDOR KD. Primary biliary cirrhosis[J]. Lancet, 2015, 386( 10003): 1565- 1575. DOI: 10.1016/S0140-6736(15)00154-3.
[9]	HASEGAWA S, YONEDA M, KURITA Y, et al. Cholestatic liver disease: Current treatment strategies and new therapeutic agents[J]. Drugs, 2021, 81( 10): 1181- 1192. DOI: 10.1007/s40265-021-01545-7.
[10]	ASSIS DN, BOWLUS CL. Recent advances in the management of primary sclerosing cholangitis[J]. Clin Gastroenterol Hepatol, 2023, 21( 8): 2065- 2075. DOI: 10.1016/j.cgh.2023.04.004.
[11]	ALBILLOS A, DE GOTTARDI A, RESCIGNO M. The gut-liver axis in liver disease: Pathophysiological basis for therapy[J]. J Hepatol, 2020, 72( 3): 558- 577. DOI: 10.1016/j.jhep.2019.10.003.
[12]	GUI WF, HOLE MJ, MOLINARO A, et al. Colitis ameliorates cholestatic liver disease via suppression of bile acid synthesis[J]. Nat Commun, 2023, 14( 1): 3304. DOI: 10.1038/s41467-023-38840-8.
[13]	RODRIGUES CMP, MOSHAGE H. Targeting TGR5 in cholangiocyte proliferation: Default topic[J]. Gut, 2016, 65( 3): 369- 370. DOI: 10.1136/gutjnl-2015-310812.
[14]	YOKODA RT, RODRIGUEZ EA. Review: Pathogenesis of cholestatic liver diseases[J]. World J Hepatol, 2020, 12( 8): 423- 435. DOI: 10.4254/wjh.v12.i8.423.
[15]	PENZ-ÖSTERREICHER M, ÖSTERREICHER CH, TRAUNER M. Fibrosis in autoimmune and cholestatic liver disease[J]. Best Pract Res Clin Gastroenterol, 2011, 25( 2): 245- 258. DOI: 10.1016/j.bpg.2011.02.001.
[16]	KIRKLAND JL, TCHKONIA T. Cellular senescence: A translational perspective[J]. EBioMedicine, 2017, 21: 21- 28. DOI: 10.1016/j.ebiom.2017.04.013.
[17]	ZENG J, FAN JG, ZHOU HP. Bile acid-mediated signaling in cholestatic liver diseases[J]. Cell Biosci, 2023, 13( 1): 77. DOI: 10.1186/s13578-023-01035-1.
[18]	SASAKI M, IKEDA H, YAMAGUCHI J, et al. Telomere shortening in the damaged small bile ducts in primary biliary cirrhosis reflects ongoing cellular senescence[J]. Hepatology, 2008, 48( 1): 186- 195. DOI: 10.1002/hep.22348.
[19]	JALAN-SAKRIKAR N, ANWAR A, YAQOOB U, et al. Telomere dysfunction promotes cholangiocyte senescence and biliary fibrosis in primary sclerosing cholangitis[J]. JCI Insight, 2023, 8( 20): e170320. DOI: 10.1172/jci.insight.170320.
[20]	FERREIRA-GONZALEZ S, LU WY, RAVEN A, et al. Paracrine cellular senescence exacerbates biliary injury and impairs regeneration[J]. Nat Commun, 2018, 9( 1): 1020. DOI: 10.1038/s41467-018-03299-5.
[21]	JALAN-SAKRIKAR N, GUICCIARDI ME, O’HARA SP, et al. Central role for cholangiocyte pathobiology in cholestatic liver diseases[J]. Hepatology, 2024. DOI: 10.1097/HEP.0000000000001093.[ Epub ahead of print]
[22]	FLEISHMAN JS, KUMAR S. Bile acid metabolism and signaling in health and disease: Molecular mechanisms and therapeutic targets[J]. Signal Transduct Target Ther, 2024, 9( 1): 97. DOI: 10.1038/s41392-024-01811-6.
[23]	GUIXÉ-MUNTET S, QUESADA-VÁZQUEZ S, GRACIA-SANCHO J. Pathophysiology and therapeutic options for cirrhotic portal hypertension[J]. Lancet Gastroenterol Hepatol, 2024, 9( 7): 646- 663. DOI: 10.1016/S2468-1253(23)00438-7.
[24]	KÖNIGSHOFER P, HOFER BS, BRUSILOVSKAYA K, et al. Distinct structural and dynamic components of portal hypertension in different animal models and human liver disease etiologies[J]. Hepatology, 2022, 75( 3): 610- 622. DOI: 10.1002/hep.32220.
[25]	ŽÍŽALOVÁ K, NOVÁKOVÁ B, VECKA M, et al. Serum concentration of taurochenodeoxycholic acid predicts clinically significant portal hypertension[J]. Liver Int, 2023, 43( 4): 888- 895. DOI: 10.1111/liv.15481.
[26]	KEITEL V, REINEHR R, GATSIOS P, et al. The G-protein coupled bile salt receptor TGR5 is expressed in liver sinusoidal endothelial cells[J]. Hepatology, 2007, 45( 3): 695- 704. DOI: 10.1002/hep.21458.
[27]	KLINDT C, REICH M, HELLWIG B, et al. The G protein-coupled bile acid receptor TGR5(Gpbar1) modulates endothelin-1 signaling in liver[J]. Cells, 2019, 8( 11): 1467. DOI: 10.3390/cells8111467.
[28]	DEVANE J, OTT E, OLINGER EG, et al. Progressive liver, kidney, and heart degeneration in children and adults affected by TULP3 mutations[J]. Am J Hum Genet, 2022, 109( 5): 928- 943. DOI: 10.1016/j.ajhg.2022.03.015.
[29]	JIANG CY, LIAN M, MA X. A rare case mimicking congenital hepatic fibrosis[J]. Gastroenterology, 2024, 167( 6): 1087- 1090. DOI: 10.1053/j.gastro.2024.04.018.
[30]	WU BH, SHENTU XY, NAN HT, et al. A spatiotemporal atlas of cholestatic injury and repair in mice[J]. Nat Genet, 2024, 56( 5): 938- 952. DOI: 10.1038/s41588-024-01687-w.
[31]	IMAM MH, SINAKOS E, GOSSARD AA, et al. High-dose ursodeoxycholic acid increases risk of adverse outcomes in patients with early stage primary sclerosing cholangitis[J]. Aliment Pharmacol Ther, 2011, 34( 10): 1185- 1192. DOI: 10.1111/j.1365-2036.2011.04863.x.
[32]	TRAUNER M, FICKERT P, TRIVEDI P, et al. Norucholic acid for the treatment of primary sclerosing cholangitis: Baseline data from a phase III trial[J]. J Hepatol, 2023, 78: S403. DOI: 10.1016/s0168-8278(23)01064-4.
[33]	SANYAL AJ, RATZIU V, LOOMBA R, et al. Results from a new efficacy and safety analysis of the REGENERATE trial of obeticholic acid for treatment of pre-cirrhotic fibrosis due to non-alcoholic steatohepatitis[J]. J Hepatol, 2023, 79( 5): 1110- 1120. DOI: 10.1016/j.jhep.2023.07.014.
[34]	US Food and Drug Administration. Serious liver injury being observed in patients without cirrhosis taking Ocaliva(obeticholic acid) to treat primary biliary cholangitis[EB/OL]. https://www.fda.gov/drugs/drug-safety-and-availability/serious-liver-injury-being-observed-patients-without-cirrhosis-taking-ocaliva-obeticholic-acid-treat. https: //www.fda.gov/drugs/drug-safety-and-availability/serious-liver-injury-being-observed-patients-without-cirrhosis-taking-ocaliva-obeticholic-acid-treat
[35]	ERSTAD DJ, FARRAR CT, GHOSHAL S, et al. Molecular magnetic resonance imaging accurately measures the antifibrotic effect of EDP-305, a novel farnesoid X receptor agonist[J]. Hepatol Commun, 2018, 2( 7): 821- 835. DOI: 10.1002/hep4.1193.
[36]	SORDA JA, GONZÁLEZ BALLERGA E, BARREYRO FJ, et al. Bezafibrate therapy in primary biliary cholangitis refractory to ursodeoxycholic acid: A longitudinal study of paired liver biopsies at 5 years of follow up[J]. Aliment Pharmacol Ther, 2021, 54( 9): 1202- 1212. DOI: 10.1111/apt.16618.
[37]	BOWLUS CL, GALAMBOS MR, ASPINALL RJ, et al. A phase II, randomized, open-label, 52-week study of seladelpar in patients with primary biliary cholangitis[J]. J Hepatol, 2022, 77( 2): 353- 364. DOI: 10.1016/j.jhep.2022.02.033.
[38]	FUCHS CD, TRAUNER M. Role of bile acids and their receptors in gastrointestinal and hepatic pathophysiology[J]. Nat Rev Gastroenterol Hepatol, 2022, 19( 7): 432- 450. DOI: 10.1038/s41575-021-00566-7.
[39]	HEMPFLING W, GRUNHAGE F, DILGER K, et al. Pharmacokinetics and pharmacodynamic action of budesonide in early-and late-stage primary biliary cirrhosis[J]. Hepatology, 2003, 38( 1): 196- 202. DOI: 10.1053/jhep.2003.50266.
[40]	NISHIO T, HU RL, KOYAMA Y, et al. Activated hepatic stellate cells and portal fibroblasts contribute to cholestatic liver fibrosis in MDR2 knockout mice[J]. J Hepatol, 2019, 71( 3): 573- 585. DOI: 10.1016/j.jhep.2019.04.012.
[41]	TRAUNER M, FUCHS CD. Novel therapeutic targets for cholestatic and fatty liver disease[J]. Gut, 2022, 71( 1): 194- 209. DOI: 10.1136/gutjnl-2021-324305.
[42]	BAGHDASARYAN A, CLAUDEL T, GUMHOLD J, et al. Dual farnesoid X receptor/TGR5 agonist INT-767 reduces liver injury in the Mdr2^-/-(Abcb4^-/-) mouse cholangiopathy model by promoting biliary HCO 3 - output[J]. Hepatology, 2011, 54( 4): 1303- 1312. DOI: 10.1002/hep.24537.
[43]	GRACIA-SANCHO J, MARRONE G, FERNÁNDEZ-IGLESIAS A. Hepatic microcirculation and mechanisms of portal hypertension[J]. Nat Rev Gastroenterol Hepatol, 2019, 16( 4): 221- 234. DOI: 10.1038/s41575-018-0097-3.
[44]	ZHU CP, LIU SQ, WANG KQ, et al. Targeting 5-hydroxytryptamine receptor 1A in the portal vein to decrease portal hypertension[J]. Gastroenterology, 2024, 167( 5): 993- 1007. DOI: 10.1053/j.gastro.2024.06.007.
[45]	MOUSA OY, JURAN BD, MCCAULEY BM, et al. Bile acid profiles in primary sclerosing cholangitis and their ability to predict hepatic decompensation[J]. Hepatology, 2021, 74( 1): 281- 295. DOI: 10.1002/hep.31652.

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Cholestatic liver disease and portal hypertension

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