Prospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 18, 2016; 8(17): 739-748
Published online Jun 18, 2016. doi: 10.4254/wjh.v8.i17.739
Circulating insulin-like growth factor-binding protein 3 as prognostic biomarker in liver cirrhosis
Carina Gabriela Correa, Bruno da Silveira Colombo, Marcelo Fernando Ronsoni, Pedro Eduardo Soares e Silva, Leonardo Fayad, Telma Erotides Silva, Letícia Muraro Wildner, Maria Luiza Bazzo, Esther Buzaglo Dantas-Correa, Janaína Luz Narciso-Schiavon, Leonardo de Lucca Schiavon
Carina Gabriela Correa, Bruno da Silveira Colombo, Marcelo Fernando Ronsoni, Pedro Eduardo Soares e Silva, Leonardo Fayad, Telma Erotides Silva, Esther Buzaglo Dantas-Correa, Janaína Luz Narciso-Schiavon, Leonardo de Lucca Schiavon, Division of Gastroenterology, Federal University of Santa Catarina, Florianópolis, Santa Catarina 88.040-001, Brazil
Letícia Muraro Wildner, Maria Luiza Bazzo, Department of Clinical Analysis, Federal University of Santa Catarina, Florianópolis, Santa Catarina 88.040-970, Brazil
Author contributions: Narciso-Schiavon JL and Schiavon LL designed the research; Correa CG, Colombo BS, Ronsoni MF, Soares e Silva PE, Fayad L, Silva TE and Dantas-Correa EB performed the research; Wildner LM and Bazzo ML contributed with the specific laboratory analysis and sample handling; Correa CG and Schiavon LL analyzed the data and wrote the paper.
Institutional review board statement: The study was reviewed and approved by the Federal University of Santa Catarina Institutional Review Board.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Nothing to report.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at leo-jf@uol.com.br. Participants gave informed consent for data sharing.
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: Dr. Leonardo de Lucca Schiavon, Division of Gastroenterology, Federal University of Santa Catarina, Rua Deputado Antonio Edu Vieira 1310, casa 217, Bairro Pantanal, Florianópolis, Santa Catarina 88.040-001, Brazil. leo-jf@uol.com.br
Telephone: +55-48-32096854 Fax: +55-48-32096854
Received: February 26, 2016
Peer-review started: February 26, 2016
First decision: March 23, 2016
Revised: May 3, 2016
Accepted: May 17, 2016
Article in press: May 27, 2016
Published online: June 18, 2016
Processing time: 109 Days and 10.7 Hours
Abstract

AIM: To investigate the prognostic significance of insulin-like growth factor-binding protein 3 (IGFBP-3) in patients with cirrhosis.

METHODS: Prospective study that included two cohorts: outpatients with stable cirrhosis (n = 138) and patients hospitalized for acute decompensation (n = 189). Development of complications, mortality or liver transplantation was assessed by periodical phone calls and during outpatient visits. The cohort of stable cirrhosis also underwent clinical and laboratory evaluation yearly (2013 and 2014) in predefined study visits. In patients with stable cirrhosis, IGFBP-3 levels were measured at baseline (2012) and at second re-evaluation (2014). In hospitalized subjects, IGFBP-3 levels were measured in serum samples collected in the first and in the third day after admission and stored at -80 °C. IGFBP-3 levels were measured by immunochemiluminescence.

RESULTS: IGFBP-3 levels were lower in hospitalized patients as compared to outpatients (0.94 mcg/mL vs 1.69 mcg/mL, P < 0.001) and increased after liver transplantation (3.81 mcg/mL vs 1.33 mcg/mL, P = 0.008). During the follow-up of the stable cohort, 17 patients died and 11 received liver transplantation. Bivariate analysis showed that death or transplant was associated with lower IGFBP-3 levels (1.44 mcg/mL vs 1.74 mcg/mL, P = 0.027). The Kaplan-Meier transplant-free survival probability was 88.6% in patients with IGFBP-3 ≥ 1.67 mcg/mL and 72.1% for those with IGFBP3 < 1.67 mcg/mL (P = 0.015). In the hospitalized cohort, 30-d mortality was 24.3% and was independently associated with creatinine, INR, SpO2/FiO2 ratio and IGFBP-3 levels in the logistic regression. The 90-d transplant-free survival probability was 80.4% in patients with IGFBP-3 ≥ 0.86 mcg/mL and 56.1% for those with IGFBP3 < 0.86 mcg/mL (P < 0.001).

CONCLUSION: Lower IGFBP-3 levels were associated with worse outcomes in patients with cirrhosis, and might represent a promising prognostic tool that can be incorporated in clinical practice.

Keywords: Liver cirrhosis; Acute decompensation; Insulin-like growth factor binding protein 3; Acute-on-chronic liver failure; Prognosis

Core tip: Insulin-like growth factor-binding protein 3 (IGFBP-3) levels are decreased in cirrhosis and seem to correlate with the intensity of hepatic dysfunction, but its prognostic significance is uncertain. In this prospective cohort study, IGFBP-3 levels correlated with variables associated with the intensity of liver dysfunction in both outpatients with stable cirrhosis and in subjects hospitalized for acute decompensation. IGFBP-3 levels increased significantly after discharge and after liver transplantation. Lower IGFBP-3 levels were associated with poor outcomes in both outpatients with stable cirrhosis and in those hospitalized for acute decompensation, suggesting that it can be used in clinical practice as a prognostic biomarker in cirrhosis.