Angiopoietin-2/angiopoietin-1 as non-invasive biomarker of cirrhosis in chronic hepatitis C

Abstract

AIMTo evaluate the efficacy of peripheral blood concentrations of angiopoietins (Ang) as cirrhosis biomarkers of chronic hepatitis C (CHC).METHODSAng1 and Ang2 serum levels were measured by enzyme-linked immunosorbent assays (ELISA) in samples from 179 cirrhotic and non-cirrhotic CHC patients, classified according to the METAVIR system. Groups were compared by non-parametric Mann-Whitney U test. Subsequently, the association of peripheral concentrations of angiopoietins with the stage of fibrosis was analyzed using Spearman correlation test. Finally, the accuracy, sensitivity and specificity of circulating angiopoietins for cirrhosis diagnosis were determined by the study of the respective area under the curve of receiver operator characteristics (AUC-ROC).RESULTSPeripheral blood concentrations of Ang1 and Ang2 in CHC patients were significantly related to fibrosis. While Ang1 was decreased in cirrhotic subjects compared to non-cirrhotic (P < 0.0001), Ang2 was significantly increased as CHC progressed to the end stage of liver disease (P < 0.0001). Consequently, Ang2/Ang1 ratio was notably amplified and significantly correlated with fibrosis (P < 0.0001). Interestingly, the individual performance of each angiopoietin for the diagnosis of cirrhosis reached notable AUC-ROC values (above 0.7, both), but the Ang2/Ang1 ratio was much better (AUC-ROC = 0.810) and displayed outstanding values of sensitivity (71%), specificity (84%) and accuracy (82.1%) at the optimal cut-off (10.33). Furthermore, Ang2/Ang1 ratio improved the performance of many other previously described biomarkers or scores of liver cirrhosis in CHC.CONCLUSIONAng2/Ang1 ratio might constitute a useful tool for monitoring the progression of chronic liver disease towards cirrhosis and play an important role as therapeutic target.

Inhibition of NF-κB signaling pathway induces apoptosis and suppresses proliferation and angiogenesis of human fibroblast-like synovial cells in rheumatoid arthritis

“…[ 27 ] The concentration of Ang1 was significantly lower in the serum of cirrhotic patients compared the concentration in the non-cirrhotic ones, and Ang2 serum levels were higher in patients with cirrhosis. [ 28 ] Zhao et al [ 29 ] demonstrated that Ang2 activated the AT1R/PI3K/Akt pathway, which further activated NF-κB, consequently leading to an increased expression of matrix metalloproteinase (MMP)-2 and MMP-9 and migration in breast cancer cells. In consistent with our findings, activated NF-κB pathway was attributed to HFLS acceleration, thus facilitating the progress of RA.…”

Clinical and prognostic significance of circulating levels of angiopoietin-1 and angiopoietin-2 in hepatocellular carcinoma

“…Consistent with our results, a retrospective study by Hernández-Bartolomé et al . [29] analyzing 179 patients had previously demonstrated that although Ang-1 was decreased in cirrhotic compared with non-cirrhotic patients, Ang-2 was significantly increased as the stage of liver disease progressed. Moreover, these authors demonstrated that the ratio of serum Ang-2 to Ang-1 displayed notable accuracy (82.1%) for the diagnosis of cirrhosis at the optimal cut-off.…”

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 ].…”