Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2015; 21(37): 10662-10668
Published online Oct 7, 2015. doi: 10.3748/wjg.v21.i37.10662
Plasma betatrophin levels in patients with liver cirrhosis
Maria Teresa Arias-Loste, Maria Teresa García-Unzueta, Susana Llerena, Paula Iruzubieta, Angela Puente, Joaquín Cabezas, Carmen Alonso, Antonio Cuadrado, José Antonio Amado, Javier Crespo, Emilio Fábrega
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
Maria Teresa García-Unzueta, José Antonio Amado, Endocrinology Unit, Marqués de Valdecilla University Hospital, Instituto de Investigación Sanitaria Valdecilla, Avenida Valdecilla s/n, 39008 Santander, Cantabria, Spain
Author contributions: Arias-Loste MT, García-Unzueta MT, Amado JA, Crespo J, Fábrega E contributed equally to this work; Arias-Loste MT, García-Unzueta MT, Amado JA, Crespo J, Fábrega E designed the research; García-Unzueta MT, Llerena S, Iruzubieta P, Puente A, Cabezas J, Alonso C, Cuadrado A performed the research; Arias-Loste MT, García-Unzueta MT, Cuadrado A, Amado JA, Crespo J, Fábrega E analyzed the data; and Arias-Loste MT, García-Unzueta MT, Amado JA, Crespo J, Fábrega E wrote the paper.
Institutional review board statement: The present study has been reviewed and approved by the Comite Etico de Cantabria Institutional Review Board.
Informed consent statement: All study participants gave their specific written consent prior to study enrollment.
Conflict-of-interest statement: Authors declare no conflict of interests.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Emilio Fábrega, PhD, MD, Gastroenterology and Hepatology Unit, Marqués de Valdecilla University Hospital, Instituto de Investigación Sanitaria Valdecilla, Avenida Valdecilla s/n, 39008 Santander, Cantabria, Spain. digfge@humv.es
Telephone: +34-42-202544 Fax: +34-42-202544
Received: February 24, 2015
Peer-review started: February 26, 2015
First decision: April 13, 2015
Revised: April 18, 2015
Accepted: July 8, 2015
Article in press: July 8, 2015
Published online: October 7, 2015
Abstract

AIM: 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).

CONCLUSION: 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.

Keywords: Liver cirrhosis, Betatrophin, Insulin resistance, Betatrophin liver, Betatrophin insulin

Core tip: Recently, Douglas A. Melton’s group from Harvard University reported the identification of betatrophin, a circulating protein secreted from the liver under insulin resistant states. Insulin resistance is common in patients with cirrhosis. In our study we confirm that betatrophin is increased in patients with liver cirrhosis, and the increase in plasma betatrophin levels is related to the severity of cirrhosis, and the emergence of insulin resistance. These preliminary results show that betatrophin may contribute to counteract, at least in part, insulin resistance in patients with cirrhosis.