Melania Manco1, Nadia Panera2, Annalisa Crudele2, Maria Rita Braghini2, Marzia Bianchi2, Donatella Comparcola3, Rita De Vito4, Giuseppe Maggiore3, Anna Alisi5. 1. Multifactorial Disease and Complex Phenotype Research Area, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. 2. Research Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. 3. Unit of Hepatology, Gastroenterology, and Nutrition, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. 4. Unit of Pathology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. 5. Research Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. anna.alisi@opbg.net.
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.
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.
Authors: Montse Pauta; Jordi Ribera; Pedro Melgar-Lesmes; Gregori Casals; Juan Rodríguez-Vita; Vedrana Reichenbach; Guillermo Fernandez-Varo; Blai Morales-Romero; Ramon Bataller; Javier Michelena; Jose Altamirano; Wladimiro Jiménez; Manuel Morales-Ruiz Journal: Liver Int Date: 2014-03-11 Impact factor: 5.828
Authors: Sander Lefere; Frederique Van de Velde; Anne Hoorens; Sarah Raevens; Sanne Van Campenhout; Astrid Vandierendonck; Sara Neyt; Bert Vandeghinste; Christian Vanhove; Charlotte Debbaut; Xavier Verhelst; Jo Van Dorpe; Christophe Van Steenkiste; Christophe Casteleyn; Bruno Lapauw; Hans Van Vlierberghe; Anja Geerts; Lindsey Devisscher Journal: Hepatology Date: 2019-02-12 Impact factor: 17.425