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

Background: Portal hypertension (PH) does not resolve in a considerable proportion of patients who achieved HCV-cure. Aims: To investigate (i)whether HCV-cure impacts cytokines that orchestrate angiogenesis (i.e.,Ang1/Ang2/VEGF) and fibrogenesis (i.e.,PDGF/TGF-beta) and (ii)whether their changes reflect PH-evolution and its complications. Methods: 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. Results: Following HCV-cure, we observed a decrease in Ang2/TGF-beta, 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. Conclusions: HCV-cure decreases circulating Ang2 - a mediator/indicator of dysangiogenesis/endothelial dysfunction, as well as TGF-beta - 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. (c) 2022 The Author(s). Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.