Abnormalities of liver sinusoidal endothelial cells in primary biliary cholangitis

Liver sinusoidal endothelial cells (LSECs) may have a critical role in the pathogenesis of primary biliary cholangitis (PBC) that has not been investigated.

To investigate the role of LSECs in PBC.

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.

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.

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.