Thalassinos E, Notas G, Xidakis C, Drygiannakis I, Sfakianaki O, Tsomidis I, Kouroumalis E. Abnormalities of liver sinusoidal endothelial cells in primary biliary cholangitis. World J Exp Med 2026; 16(1): 114313 [DOI: 10.5493/wjem.v16.i1.114313]
Corresponding Author of This Article
Elias Kouroumalis, MD, PhD, Emeritus Professor, Liver Research Laboratory, University of Crete Medical School, 13 Kalokerinou Street, Voutes, Heraklion 71003, Greece. kouroumi@uoc.gr
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Mar 20, 2026 (publication date) through Mar 20, 2026
Times Cited of This Article
Times Cited (0)
Journal Information of This Article
Publication Name
World Journal of Experimental Medicine
ISSN
2220-315x
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Share the Article
Thalassinos E, Notas G, Xidakis C, Drygiannakis I, Sfakianaki O, Tsomidis I, Kouroumalis E. Abnormalities of liver sinusoidal endothelial cells in primary biliary cholangitis. World J Exp Med 2026; 16(1): 114313 [DOI: 10.5493/wjem.v16.i1.114313]
World J Exp Med. Mar 20, 2026; 16(1): 114313 Published online Mar 20, 2026. doi: 10.5493/wjem.v16.i1.114313
Abnormalities of liver sinusoidal endothelial cells in primary biliary cholangitis
Evangelos Thalassinos, George Notas, Costantinos Xidakis, Ioannis Drygiannakis, Ourania Sfakianaki, Ioannis Tsomidis, Elias Kouroumalis
Evangelos Thalassinos, Department of Medicine, Venizeleion General Hospital, Heraklion 71409, Crete, Greece
George Notas, Laboratory of Experimental Endocrinology, School of Medicine, University of Crete, Voutes Campus, Heraklion 70013, Crete, Greece
Costantinos Xidakis, Ourania Sfakianaki, Ioannis Tsomidis, Elias Kouroumalis, Laboratory of Gastroenterology and Hepatology, School of Medicine, University of Crete, Voutes Campus, Heraklion 70013, Crete, Greece
Ioannis Drygiannakis, Elias Kouroumalis, Department of Gastroenterology, University Hospital, Heraklion 71500, Crete, Greece
Elias Kouroumalis, Liver Research Laboratory, University of Crete Medical School, Heraklion 71003, Crete, Greece
Co-first authors: Evangelos Thalassinos and George Notas.
Author contributions: Thalassinos E and Kouroumalis E were involved in conceptualizing the study; Thalassinos E and Notas G contributed equally to this manuscript as co-first authors; Thalassinos E, Kouroumalis E, Notas G, Xidakis C, and Drygiannakis I involved in writing the draft; Notas G, Xidakis C, and Drygiannakis I were responsible for the data acquisition and statistical analysis; Sfakianaki O and Tsomidis I were involved in the revision of the draft. All authors approved the final version of the paper prior to submission.
Institutional review board statement: The study was approved by the Ethics Committee of the Venizeleion General Hospital.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Corresponding author: Elias Kouroumalis, MD, PhD, Emeritus Professor, Liver Research Laboratory, University of Crete Medical School, 13 Kalokerinou Street, Voutes, Heraklion 71003, Greece. kouroumi@uoc.gr
Received: September 18, 2025 Revised: October 19, 2025 Accepted: January 5, 2026 Published online: March 20, 2026 Processing time: 180 Days and 14.3 Hours
Abstract
BACKGROUND
Liver sinusoidal endothelial cells (LSECs) may have a critical role in the pathogenesis of primary biliary cholangitis (PBC) that has not been investigated.
AIM
To investigate the role of LSECs in PBC.
METHODS
We studied the levels of soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1 and soluble E-selectin and the tissue plasminogen activator (t-PA) and its inhibitor in the serum of 30 PBC patients before and 25 patients after treatment with ursodeoxycholic acid (UDCA). Moreover, immortalized endothelial cells (EA.hy926) were incubated with serum from patients with PBC, hepatitis C virus (HCV) and normal controls for up to 24 hours. The expression of endothelin (ET) 1, ET2, ET3, and ET receptors A and B were also measured by quantitative polymerase chain reaction.
RESULTS
Vascular cell adhesion molecule and intercellular adhesion molecule were significantly increased in PBC and HCV with the highest values found in PBC patients. UDCA had no effect. Levels were significantly higher in late PBC (stages III-IV), compared with early PBC (stages I-II). t-PA was significantly increased in PBC but not in HCV. Higher values were obtained in late PBC. UDCA decreased t-PA. Plasminogen activator inhibitor-1 levels were similar in all groups. Expression of endothelin 1, endothelin 2, and endothelin 3 significantly varied at different time points. ET receptors A was decreased at 2 hours and 6 hours in PBC, and at 2 hours and 24 hours in HCV. ET receptors B was reduced at 2 hours and 24 hours in both PBC and HCV.
CONCLUSION
Endothelial adhesion molecules are abnormal in PBC particularly in the late fibrotic stages. ET and their receptors are reduced in LSECs after incubation with PBC and HCV sera, findings that might be related to pathogenesis.
Core Tip: Liver sinusoidal endothelial cells (LSECs) are implicated in the pathogenesis of various liver diseases including primary biliary cholangitis (PBC). In the present study, we demonstrated that LSECs biomarkers are significantly altered in the serum of patients with PBC but also in patients with chronic hepatitis C virus. Moreover, we incubated the human endothelial cell line EA.hy926 with sera from patients with PBC and hepatitis C virus and found that the expression of endothelins and their receptors significantly fluctuated at different time points. Collectively, these findings indicate that LSECs may be implicated in the pathogenesis of PBC.
