Intrahepatic angiopoietin‐2 correlates with chronic hepatitis C progression and is induced in hepatitis C virus replicon systems

Abstract

Hepatitis C virus induces Ang2 expression in hepatocytes through different signalling routes which may lead to the disregulation of vascular homeostasis in the liver. Thus, pharmacologic intervention on Ang2 signalling might constitute an important therapeutic tool.

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

“…The decrease of Ang2 showed some correlation with dynamics in HVPG but also VWF (both correlations not statistically significant after Bonferroni correction) -a marker of endothelial dysfunction, which has been linked to clinical events in patients with CSPH, independently from HVPG [ 34 , 45 ]. Although hepatocytes have been suggested as a cellular source of Ang2 in CHC [43] , recent observations in NASH patients identified endothelial cells are the main contributors [20] .…”

“…Of note, the AUROC of Ang2 for pronounced PH (i.e., HVPG ≥16 mmHg) tended to be even higher with a value exceeding 0.8 at FU. However, Ang2 is not merely a marker of ACLD/PH, as blockade of Ang2 prevents structural changes in the hepatic microvasculature in a rat model of CCl4-induced cirrhosis and ameliorates hepatic inflammation and fibrosis [43] and endothelial dysfunction and hepatocarcinogenesis in non-alcoholic liver disease (NASH) models [20] . The decrease of Ang2 showed some correlation with dynamics in HVPG but also VWF (both correlations not statistically significant after Bonferroni correction) -a marker of endothelial dysfunction, which has been linked to clinical events in patients with CSPH, independently from HVPG [ 34 , 45 ].…”

Profibrotic Signaling and HCC Risk during Chronic Viral Hepatitis: Biomarker Development

“…In patients with HCV-associated cirrhosis and HCC, several angiogenesis soluble factors were significantly upregulated in the blood plasma, including TIMP-1, TIMP-2, HGF, angiopoietin 1, angiopoietin 2, VEGFA, IP-10, PDGF, KGF and FGF. AUROC analysis highlighted especially the potential of angiopoietin 2, a growth factor that belongs to the angiopoietin/Tie signaling pathway [ 119 , 120 , 121 ]. Additionally, CCL20, a secreted chemokine detected in HCCs, promotes blood vessel formation during chronic HCV infection [ 122 ].…”