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Angiopoietin-2 levels correlates with disease activity in children with nonalcoholic fatty liver disease

Abstract

Background

Nonalcoholic fatty liver disease (NAFLD), a chronic liver disease in children, ranges from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). We investigated the role of Angiopoietin-2 (Ang-2) as a biomarker for pediatric NAFLD-related liver damage.

Methods

We assessed the plasma levels of Ang-2 and cytokeratin-18 (CK18) fragments and their association with histologic activity in 76 children with NAFLD and 28 controls.

Results

The mean plasma levels of Ang-2 and CK18 were higher in children with NAFLD than in age-matched controls (Ang-2 155.4 ± 72.5 vs 7.5 ± 2.3 ng/mL, p < 0.001; CK18 390.4 ± 145.6 vs 193.9 ± 30.8 IU/L, p < 0.001). Ang-2 was significantly increased (p < 0.0001) in children with NASH (N = 41) while CK18 was significantly increased (p = 0.002) in children with fibrosis (N = 47). Ang-2 levels accurately predicted NASH (AUROC 0.911; 95% CI 0.844–0.979; p < 0.0001), while CK18 predicted both NASH (AUROC 0.827; 95% CI 0.735–0.919; p < 0.0001) and fibrosis (AUROC 0.724; 95% CI 0.611–0.837; p = 0.001). Ang-2 and CK18 in combination were good predictors of NASH with a sensitivity of 71.4% and a specificity of 100%.

Conclusions

In conclusion, our data suggested Ang-2 as a suitable biomarker of NASH in the pediatric population. However, our findings need external validation in other cohorts.

Impact

  • Several circulating factors have been extensively studied as potential biomarkers for NASH.

  • Angiopoietin-2 circulating levels are increased in children with NAFLD and are associated with NASH.

  • Angiopoietin-2 levels are more efficient than CK18 levels at assessing the most severe form of disease, and the combining of these two biomarkers reached a positive predictive value of 100% for NASH.

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Fig. 1: Assessment of Ang-2 and CK18 circulating levels.
Fig. 2: ROC curves for Ang-2 and CK18 in predicting NASH and fibrosis among NAFLD patients.

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Acknowledgements

The authors would like to thank our nursing staff members (Giulia Pace, Anna Maria Conti, and Loriana Giammaria) for their precious assistance in caring patients and in recruiting them for this project.

Funding

This work was supported by Italian Ministry of Health (Fondi-di-Ricerca Corrente 2020) to A.A.

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Contributions

Conceptualization: M.M., N.P. and A.A.; methodology: A.C., D.C., M.B. and R.D.V.; formal analysis: M.M., N.P., A.C. and M.R.B.; data curation: M.M., N.P., M.R.B., M.B., R.D.V., G.M. and A.A.; writing—original draft preparation: N.P., D.C. and G.M.; writing—review and editing: M.M. and A.A.; supervision and project administration: A.A.; funding acquisition: A.A. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Anna Alisi.

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Manco, M., Panera, N., Crudele, A. et al. Angiopoietin-2 levels correlates with disease activity in children with nonalcoholic fatty liver disease. Pediatr Res 91, 1781–1786 (2022). https://doi.org/10.1038/s41390-021-01666-5

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