title: Angiopoietin-2/angiopoietin-1 as non-invasive biomarker of cirrhosis in chronic hepatitis C.
abstract: OBJECTIVE
  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-WhitneyUtest. 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Ángel Hernández-Bartolomé, Rosario López-Rodríguez, Leticia González-Moreno, Yolanda Real-Martínez, Luisa García-Buey, Ricardo Moreno-Otero, Paloma Sanz-Cameno, Liver Unit, Gastroenterology Service, Instituto Investigación Sanitaria Princesa, IIS-IP, 28006 Madrid, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Hernández-Bartolomé
authors.affiliation: Ángel Hernández-Bartolomé, Rosario López-Rodríguez, Leticia González-Moreno, Yolanda Real-Martínez, Luisa García-Buey, Ricardo Moreno-Otero, Paloma Sanz-Cameno, Liver Unit, Gastroenterology Service, Instituto Investigación Sanitaria Princesa, IIS-IP, 28006 Madrid, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: López-Rodríguez
authors.affiliation: Ángel Hernández-Bartolomé, Rosario López-Rodríguez, Leticia González-Moreno, Yolanda Real-Martínez, Luisa García-Buey, Ricardo Moreno-Otero, Paloma Sanz-Cameno, Liver Unit, Gastroenterology Service, Instituto Investigación Sanitaria Princesa, IIS-IP, 28006 Madrid, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Borque
authors.affiliation: Ángel Hernández-Bartolomé, Rosario López-Rodríguez, Leticia González-Moreno, Yolanda Real-Martínez, Luisa García-Buey, Ricardo Moreno-Otero, Paloma Sanz-Cameno, Liver Unit, Gastroenterology Service, Instituto Investigación Sanitaria Princesa, IIS-IP, 28006 Madrid, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: González-Moreno
authors.affiliation: Ángel Hernández-Bartolomé, Rosario López-Rodríguez, Leticia González-Moreno, Yolanda Real-Martínez, Luisa García-Buey, Ricardo Moreno-Otero, Paloma Sanz-Cameno, Liver Unit, Gastroenterology Service, Instituto Investigación Sanitaria Princesa, IIS-IP, 28006 Madrid, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Real-Martínez
authors.affiliation: Ángel Hernández-Bartolomé, Rosario López-Rodríguez, Leticia González-Moreno, Yolanda Real-Martínez, Luisa García-Buey, Ricardo Moreno-Otero, Paloma Sanz-Cameno, Liver Unit, Gastroenterology Service, Instituto Investigación Sanitaria Princesa, IIS-IP, 28006 Madrid, Spain.
authors.forename: Luisa
authors.initials: L
authors.lastname: García-Buey
authors.affiliation: Ángel Hernández-Bartolomé, Rosario López-Rodríguez, Leticia González-Moreno, Yolanda Real-Martínez, Luisa García-Buey, Ricardo Moreno-Otero, Paloma Sanz-Cameno, Liver Unit, Gastroenterology Service, Instituto Investigación Sanitaria Princesa, IIS-IP, 28006 Madrid, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Moreno-Otero
authors.affiliation: Ángel Hernández-Bartolomé, Rosario López-Rodríguez, Leticia González-Moreno, Yolanda Real-Martínez, Luisa García-Buey, Ricardo Moreno-Otero, Paloma Sanz-Cameno, Liver Unit, Gastroenterology Service, Instituto Investigación Sanitaria Princesa, IIS-IP, 28006 Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Sanz-Cameno
mesh_terms: D000328:Adult; D000368:Aged; D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000175:diagnosis; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis / Q000821:virology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C467630:ANGPT1 protein, human; C586513:ANGPT2 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015415:Biomarkers
keywords: Angiogenesis; Angiopoietin-1; Angiopoietin-2; Area under the curve of receiver operator characteristics; Biomarker; Chronic hepatitis C; Cirrhosis; Liver fibrosis