Angiopoietin 2 levels decrease after HCV-cure and reflect the evolution of portal hypertension

Portal hypertension (PH) does not resolve in a considerable proportion of patients who achieved HCV-cure. To investigate (i)whether HCV-cure impacts cytokines that orchestrate angiogenesis (i.e.,Ang1/Ang2/VEGF) and fibrogenesis (i.e.,PDGF/TGF-β) and (ii)whether their changes reflect PH-evolution and...

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Published in:Digestive and liver disease 2022-09, Vol.54 (9), p.1222-1229
Main Authors: Bauer, David, Kozbial, Karin, Schwabl, Philipp, Chromy, David, Simbrunner, Benedikt, Stättermayer, Albert F., Pinter, Matthias, Steindl-Munda, Petra, Trauner, Michael, Ferenci, Peter, Reiberger, Thomas, Mandorfer, Mattias
Format: Article
Language:English
Subjects:
Angiogenesis
Angiopoietin-2
Cirrhosis
Cytokines
HCV
Hepatic venous pressure gradient
Hepatitis C
Humans
Hypertension, Portal
Liver Cirrhosis
Portal Pressure
SVR
Transforming Growth Factor beta
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Summary:Portal hypertension (PH) does not resolve in a considerable proportion of patients who achieved HCV-cure. To investigate (i)whether HCV-cure impacts cytokines that orchestrate angiogenesis (i.e.,Ang1/Ang2/VEGF) and fibrogenesis (i.e.,PDGF/TGF-β) and (ii)whether their changes reflect PH-evolution and its complications. We measured plasma levels of cytokines and von Willebrand factor (VWF) and assessed hepatic venous pressure gradient (HVPG) before/after HCV-cure in 66 patients with pre-treatment PH and 23 patients without advanced disease, who served as controls. Following HCV-cure, we observed a decrease in Ang2/TGF-β, but no changes in the other cytokines. The differences in circulating cytokine profiles in PH patients persisted after removing the primary etiological factor. Patients with pre-treatment HVPG≥10 mmHg with HVPG-reduction≥10% had a more pronounced relative decrease in Ang2. Finally, post-treatment Ang2 predicted FU-HVPG≥16 mmHg/decompensation with AUROC-values of 0.804/0.835. HCV-cure decreases circulating Ang2 – a mediator/indicator of dysangiogenesis/endothelial dysfunction, as well as TGF-β – a profibrogenic cytokine. The dynamics of Ang2 mirrored those of PH, rendering FU-Ang2 a non-invasive test for pronounced PH at FU that also predicts hepatic decompensation. The pathophysiological significance of the persistently altered cytokine levels for mechanisms that hinder the PH-regression warrants further study.
ISSN:1590-8658
1878-3562
DOI:10.1016/j.dld.2022.02.013