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, 22 (44), 9744-9751

Angiopoietin-2/angiopoietin-1 as Non-Invasive Biomarker of Cirrhosis in Chronic Hepatitis C


Angiopoietin-2/angiopoietin-1 as Non-Invasive Biomarker of Cirrhosis in Chronic Hepatitis C

Ángel Hernández-Bartolomé et al. World J Gastroenterol.


Aim: To evaluate the efficacy of peripheral blood concentrations of angiopoietins (Ang) as cirrhosis biomarkers of chronic hepatitis C (CHC).

Methods: Ang1 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).

Results: Peripheral 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.

Conclusion: Ang2/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.

Keywords: Angiogenesis; Angiopoietin-1; Angiopoietin-2; Area under the curve of receiver operator characteristics; Biomarker; Chronic hepatitis C; Cirrhosis; Liver fibrosis.

Conflict of interest statement

Conflict-of-interest statement: The authors have no conflicts of interest to declare.


Figure 1
Figure 1
Distribution serum concentrations of Ang1 (A), Ang2 (B) and Ang2/Ang1 ratio values (C) in chronic hepatitis C patients. Medians are represented by horizontal lines. Statistical significance was tested using Mann-Whitney U-test. Ang1: Angiopoietin 1; Ang2: Angiopoietin 2.
Figure 2
Figure 2
The receiver operating characteristic curve analysis on the abilities of Ang1, Ang2 and the Ang-2/Ang-1 ratio to diagnose. Significant fibrosis (F > 1) (A), advanced fibrosis (F > 2) (B) and cirrhosis (F > 3) (C) in patients with chronic hepatitis C. Ang1: Angiopoietin 1; Ang2: Angiopoietin 2.

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