Prospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 28, 2016; 22(12): 3441-3450
Published online Mar 28, 2016. doi: 10.3748/wjg.v22.i12.3441
Osteopontin: A non-invasive parameter of portal hypertension and prognostic marker of cirrhosis
Radan Bruha, Marie Jachymova, Jaromir Petrtyl, Karel Dvorak, Martin Lenicek, Petr Urbanek, Tomislav Svestka, Libor Vitek
Radan Bruha, Jaromir Petrtyl, Karel Dvorak, Tomislav Svestka, 4th Department of Internal Medicine, 1st Faculty of Medicine and General University Hospital, Charles University in Prague, 12808 Prague, Czech Republic
Marie Jachymova, Martin Lenicek, Libor Vitek, Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, 12808 Prague, Czech Republic
Petr Urbanek, Department of Internal Medicine, Central Military Hospital and 1st Faculty of Medicine, Charles University in Prague, 12808 Prague, Czech Republic
Author contributions: Bruha R and Jachymova M contributed to study concept; Bruha R, Petrtyl J, Urbanek P, Dvorak K and Svestka T acquired data; Bruha R and Petrtyl J drafted the manuscript; Bruha R and Lenicek M performed the statistical analysis; Petrtyl J and Lenicek M provided the technical and material support; Dvorak K, Lenicek M, Svestka T and Vitek L contributed to analysis and interpretation of data; Jachymova M, Dvorak K and Urbanek P critically revised the manuscript; Vitek L supervised the study; and all authors approved the final version of manuscript.
Supported by The Internal Grant Agency of the Czech Ministry of Health (http://iga.mzcr.cz/publicWeb/), No. NT 12290/4; the Charles University in Prague (http://www.cuni.cz/UKEN-1.html), No. SVV 260156/2015; and the Czech Ministry of Health (http://mzcr.cz), No. MZCR-RVO VFN64165.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of 1st Faculty of Medicine and General University Hospital in Prague.
Clinical trial registration statement: This study is registered at SUKL - State Institute for Drug Control of the Czech Republic (http://www.sukl.eu/modules/evaluation/detail.php?id=31445&lang=2). The registration identification number is EudraCT number: 2011-001132-30.
Informed consent statement: All study participants provided informed written consent prior to study enrolment.
Conflict-of-interest statement: The authors of this manuscript having no conflicts of interest to disclose.
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: Radan Bruha, MD, PhD, 4th Department of Internal Medicine, General University Hospital, U Nemocnice 2, 12808 Prague, Czech Republic. bruha@cesnet.cz
Telephone: +420-22-4962506 Fax: +420-22-4923524
Received: September 11, 2015
Peer-review started: September 16, 2015
First decision: November 5, 2015
Revised: December 3, 2015
Accepted: December 19, 2015
Article in press: December 21, 2015
Published online: March 28, 2016
Processing time: 194 Days and 13.7 Hours
Abstract

AIM: To investigate the relationship between osteopontin plasma concentrations and the severity of portal hypertension and to assess osteopontin prognostic value.

METHODS: A cohort of 154 patients with confirmed liver cirrhosis (112 ethylic, 108 men, age 34-72 years) were enrolled in the study. Hepatic venous pressure gradient (HVPG) measurement and laboratory and ultrasound examinations were carried out for all patients. HVPG was measured using a standard catheterization method with the balloon wedge technique. Osteopontin was measured using the enzyme-linked immunosorbent assay (ELISA) method in plasma. Patients were followed up with a specific focus on mortality. The control group consisted of 137 healthy age- and sex- matched individuals.

RESULTS: The mean value of HVPG was 16.18 ± 5.6 mmHg. Compared to controls, the plasma levels of osteopontin in cirrhotic patients were significantly higher (P < 0.001). The plasma levels of osteopontin were positively related to HVPG (P = 0.0022, r = 0.25) and differed among the individual Child-Pugh groups of patients. The cut-off value of 80 ng/mL osteopontin distinguished patients with significant portal hypertension (HVPG above 10 mmHg) at 75% sensitivity and 63% specificity. The mean follow-up of patients was 3.7 ± 2.6 years. The probability of cumulative survival was 39% for patients with HVPG > 10 mmHg and 65% for those with HVPG ≤ 10 mmHg (P = 0.0086, odds ratio (OR), 2.92, 95% confidence interval (CI): 1.09-7.76). Osteopontin showed a similar prognostic value to HVPG. Patients with osteopontin values above 80 ng/mL had significantly lower cumulative survival compared to those with osteopontin ≤ 80 ng/mL (37% vs 56%, P = 0.00035; OR = 2.23, 95%CI: 1.06-4.68).

CONCLUSION: Osteopontin is a non-invasive parameter of portal hypertension that distinguishes patients with clinically significant portal hypertension. It is a strong prognostic factor for survival.

Keywords: Cirrhosis; Complications of cirrhosis; Hepatic venous pressure gradient; Osteopontin; Portal hypertension; Prognosis; Survival prediction

Core tip: Data presented in our study are based on a 7-year follow-up interval with systematic hemodynamic evaluations of more than 150 cirrhotic patients. We report for the first time a close relationship between osteopontin (OPN) and portal hypertension. Our findings suggest that OPN in plasma could be a marker of clinically significant portal hypertension. Importantly, we found that OPN is a strong prognostic indicator in patients with liver cirrhosis; and, similar to hepatic venous pressure gradient (HVPG) value, it significantly determined survival probability. Moreover, the combination of HVPG and OPN increased the validity of prognosis.