title: Plasma betatrophin levels in patients with liver cirrhosis.
abstract: OBJECTIVE
  To investigate the plasma levels of betatrophin in patients with cirrhosis.
  
  
  METHODS
  Forty patients diagnosed at the clinic with liver cirrhosis according to biological, ultrasonographic, or histological criteria were included. The severity of cirrhosis was classified according to Pugh's modification of Child's classification and MELD score. Insulin resistance (IR) was assessed by the Homeostasis Model Assessment. A total of 20 patients showed a MELD score higher than 14. The control group consisted in 15 sex-and aged-matched subjects. Fasting blood samples were obtained for subsequent analysis. Serum insulin was determined by Liaison automated immune chemiluminiscence assay (DiaSorin S.p.A.) using a sandwich assay. The sensitivity of the assay was 0.2 μU/mL. The intra and interassay variation coefficients were < 4% and < 10%, respectively. The normal values were between 2 and 17 μU/mL. Human active betatrophin was analyzed by specific quantitative sandwich ELISA (Aviscera Bioscience). The sensitivity of the assay was 0.4 ng/mL, and the intra and interassay reproducibility were < 6% and < 10%, respectively.
  
  
  RESULTS
  Plasma betatrophin levels were significantly increased in patients with cirrhosis compared with those in healthy subjects (P = 0.0001). Betatrophin levels were also associated with disease severity, being higher in Child-Pugh C patients compared to Child-Pugh B (P < 0.0005) and in patients who displayed a MELD score higher than 14 points compared to patients with lower punctuation (P = 0.01). In addition, we found a positive correlation between plasma betatrophin levels and the severity of cirrhosis according to Child-Pugh classification (r = 0.53; P < 0.01) or MELD score (r = 0.45; P < 0.01). In the overall cohort, a moderate correlation between serum betatrophin and plasmatic bilirrubin (r = 0.39; P < 0.01) has been observed, as well as an inverse correlation between betatrophin and albumin (r = -0.41; P < 0.01) or prothrombin time (r = -0.44; P <0.01). Moreover, insulin resistance was observed in 82.5% of the cirrhotic patients. In this group of patients, betatrophin levels were significantly higher than those in the group of patients without IR (P < 0.05).
  
  
  CONCLUSIONS
  Plasma betatrophin is increased in patients with cirrhosis. This increase is related to the severity of cirrhosis, as well as with the emergence of insulin resistance.
authors.affiliation: Maria Teresa Arias-Loste, Susana Llerena, Paula Iruzubieta, Angela Puente, Joaquín Cabezas, Carmen Alonso, Antonio Cuadrado, Javier Crespo, Emilio Fábrega, Gastroenterology and Hepatology Unit, Marqués de Valdecilla University Hospital, Instituto de Investigación Sanitaria Valdecilla, Avenida Valdecilla s/n, 39008 Santander, Cantabria, Spain.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Arias-Loste
authors.affiliation: Maria Teresa Arias-Loste, Susana Llerena, Paula Iruzubieta, Angela Puente, Joaquín Cabezas, Carmen Alonso, Antonio Cuadrado, Javier Crespo, Emilio Fábrega, Gastroenterology and Hepatology Unit, Marqués de Valdecilla University Hospital, Instituto de Investigación Sanitaria Valdecilla, Avenida Valdecilla s/n, 39008 Santander, Cantabria, Spain.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: García-Unzueta
authors.affiliation: Maria Teresa Arias-Loste, Susana Llerena, Paula Iruzubieta, Angela Puente, Joaquín Cabezas, Carmen Alonso, Antonio Cuadrado, Javier Crespo, Emilio Fábrega, Gastroenterology and Hepatology Unit, Marqués de Valdecilla University Hospital, Instituto de Investigación Sanitaria Valdecilla, Avenida Valdecilla s/n, 39008 Santander, Cantabria, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Llerena
authors.affiliation: Maria Teresa Arias-Loste, Susana Llerena, Paula Iruzubieta, Angela Puente, Joaquín Cabezas, Carmen Alonso, Antonio Cuadrado, Javier Crespo, Emilio Fábrega, Gastroenterology and Hepatology Unit, Marqués de Valdecilla University Hospital, Instituto de Investigación Sanitaria Valdecilla, Avenida Valdecilla s/n, 39008 Santander, Cantabria, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Iruzubieta
authors.affiliation: Maria Teresa Arias-Loste, Susana Llerena, Paula Iruzubieta, Angela Puente, Joaquín Cabezas, Carmen Alonso, Antonio Cuadrado, Javier Crespo, Emilio Fábrega, Gastroenterology and Hepatology Unit, Marqués de Valdecilla University Hospital, Instituto de Investigación Sanitaria Valdecilla, Avenida Valdecilla s/n, 39008 Santander, Cantabria, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Puente
authors.affiliation: Maria Teresa Arias-Loste, Susana Llerena, Paula Iruzubieta, Angela Puente, Joaquín Cabezas, Carmen Alonso, Antonio Cuadrado, Javier Crespo, Emilio Fábrega, Gastroenterology and Hepatology Unit, Marqués de Valdecilla University Hospital, Instituto de Investigación Sanitaria Valdecilla, Avenida Valdecilla s/n, 39008 Santander, Cantabria, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Cabezas
authors.affiliation: Maria Teresa Arias-Loste, Susana Llerena, Paula Iruzubieta, Angela Puente, Joaquín Cabezas, Carmen Alonso, Antonio Cuadrado, Javier Crespo, Emilio Fábrega, Gastroenterology and Hepatology Unit, Marqués de Valdecilla University Hospital, Instituto de Investigación Sanitaria Valdecilla, Avenida Valdecilla s/n, 39008 Santander, Cantabria, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Alonso
authors.affiliation: Maria Teresa Arias-Loste, Susana Llerena, Paula Iruzubieta, Angela Puente, Joaquín Cabezas, Carmen Alonso, Antonio Cuadrado, Javier Crespo, Emilio Fábrega, Gastroenterology and Hepatology Unit, Marqués de Valdecilla University Hospital, Instituto de Investigación Sanitaria Valdecilla, Avenida Valdecilla s/n, 39008 Santander, Cantabria, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuadrado
authors.affiliation: Maria Teresa Arias-Loste, Susana Llerena, Paula Iruzubieta, Angela Puente, Joaquín Cabezas, Carmen Alonso, Antonio Cuadrado, Javier Crespo, Emilio Fábrega, Gastroenterology and Hepatology Unit, Marqués de Valdecilla University Hospital, Instituto de Investigación Sanitaria Valdecilla, Avenida Valdecilla s/n, 39008 Santander, Cantabria, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Amado
authors.affiliation: Maria Teresa Arias-Loste, Susana Llerena, Paula Iruzubieta, Angela Puente, Joaquín Cabezas, Carmen Alonso, Antonio Cuadrado, Javier Crespo, Emilio Fábrega, Gastroenterology and Hepatology Unit, Marqués de Valdecilla University Hospital, Instituto de Investigación Sanitaria Valdecilla, Avenida Valdecilla s/n, 39008 Santander, Cantabria, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Crespo
authors.affiliation: Maria Teresa Arias-Loste, Susana Llerena, Paula Iruzubieta, Angela Puente, Joaquín Cabezas, Carmen Alonso, Antonio Cuadrado, Javier Crespo, Emilio Fábrega, Gastroenterology and Hepatology Unit, Marqués de Valdecilla University Hospital, Instituto de Investigación Sanitaria Valdecilla, Avenida Valdecilla s/n, 39008 Santander, Cantabria, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Fábrega
mesh_terms: D000328:Adult; D000368:Aged; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D008103:Liver Cirrhosis / Q000097:blood* / Q000473:pathology; D049449:Luminescence; D008297:Male; D008875:Middle Aged; D036361:Peptide Hormones / Q000097:blood*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: C576683:ANGPTL8 protein, human; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D036361:Peptide Hormones
keywords: Betatrophin; Betatrophin insulin; Betatrophin liver; Insulin resistance; Liver cirrhosis