Voulgaris TA, Karagiannakis D, Hadziyannis E, Manolakopoulos S, Karamanolis GP, Papatheodoridis G, Vlachogiannakos J. Serum zonulin levels in patients with liver cirrhosis: Prognostic implications. World J Hepatol 2021; 13(10): 1394-1404 [PMID: 34786174 DOI: 10.4254/wjh.v13.i10.1394]
Corresponding Author of This Article
John Vlachogiannakos, MD, PhD, Professor, Academic Department of Gastroenterology and Hepatology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, 17 Agiou Thoma Street, Athens 11527, Greece. jvlachog@hotmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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/
World J Hepatol. Oct 27, 2021; 13(10): 1394-1404 Published online Oct 27, 2021. doi: 10.4254/wjh.v13.i10.1394
Serum zonulin levels in patients with liver cirrhosis: Prognostic implications
Theodoros A Voulgaris, Dimitrios Karagiannakis, E Hadziyannis, Spilios Manolakopoulos, Georgios P Karamanolis, George Papatheodoridis, John Vlachogiannakos
Theodoros A Voulgaris, Dimitrios Karagiannakis, Spilios Manolakopoulos, Georgios P Karamanolis, George Papatheodoridis, John Vlachogiannakos, Academic Department of Gastroenterology and Hepatology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Athens 11527, Greece
E Hadziyannis, Academic Department of Medicine, Hippokrat General Hospital, National and Kapodistrian University of Athens, Athens 11527, Greece
Author contributions: Voulgaris TA was involved in the design of the trial, collected the clinical, biochemical and endoscopic data, performed the statistical analyses and wrote the initial draft; Karagiannakis D helped plan the study, developed the detailed study protocol, collected the clinical, biochemical and endoscopic data, and reviewed the manuscript; Hadziyannis E contributed to serum samples analysis; Karamanolis GP and Manolakopoulos S helped in the design of the study and reviewed the manuscript; Papatheodoridis GV was involved in the improvement of the protocol as well as in the finalization of the manuscript; Vlachogiannakos J contributed to the design of the study, the interpretation of the data, and review and finalizing of the manuscript.
Institutional review board statement: The study was reviewed and approved by the Greek Committee for the Protection of Personal Data (approval No. 1990) after the official request of the “Laiko” General Hospital Athens Attiki (Laiko Hospital Institutional Review Board Decision: 712;8/5/2017).
Conflict-of-interest statement: The authors declare having no real or potential conflicts to disclose.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at jvlavhog@hotmail.com. Consent was not obtained but the presented data are anonymized and risk of identification is low.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: John Vlachogiannakos, MD, PhD, Professor, Academic Department of Gastroenterology and Hepatology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, 17 Agiou Thoma Street, Athens 11527, Greece. jvlachog@hotmail.com
Received: February 28, 2021 Peer-review started: February 28, 2021 First decision: May 2, 2021 Revised: May 12, 2021 Accepted: September 19, 2021 Article in press: September 19, 2021 Published online: October 27, 2021 Processing time: 235 Days and 17 Hours
Abstract
BACKGROUND
Increased gut permeability and bacterial translocation play an important role in liver cirrhosis. Zonulin is a recently recognized protein involved in the disintegration of the intestinal barrier.
AIM
To investigate possible differences in serum zonulin levels among patients with different cirrhosis stages and their potential prognostic implications.
METHODS
Consecutive cirrhotic patients who attended our liver clinic were included in the study. Serum zonulin levels, clinical, radiological and biochemical data were collected at baseline. Patients who accepted participation in a regular surveillance program were followed-up for at least 12 mo.
RESULTS
We enrolled 116 cirrhotics [mean Child-Turcotte-Pugh (CTP) score: 6.2 ± 1.6; model for end-stage liver disease score: 11 ± 3.9]. The causes of cirrhosis were viral hepatitis (39%), alcohol (30%), non-alcoholic fatty liver disease (17%), and other (14%). At baseline, 53% had decompensated cirrhosis, 48% had ascites, and 32% had history of hepatic encephalopathy. Mean zonulin levels were significantly higher in patients with CTP-B class than CTP-A class (4.2 ± 2.4 ng/dL vs 3.5 ± 0.9 ng/dL, P = 0.038), with than without ascites (P = 0.006), and with than without history of encephalopathy (P = 0.011). Baseline serum zonulin levels were independently associated with the probability of decompensation at 1 year (P = 0.039), with an area under the receiving operating characteristic of 0.723 for predicting hepatic decompensation. Higher CTP score (P = 0.021) and portal vein diameter (P = 0.022) were independent predictors of mortality.
CONCLUSION
Serum zonulin levels are higher in patients with more advanced chronic liver disease and have significant prognostic value in identifying patients who will develop decompensation.
Core Tip: Zonulin is a protein that appears to play a significant role in gut barrier integrity. Increased zonulin levels and deregulation of intestinal permeability have been demonstrated in patients suffering from celiac disease or type 2 diabetes. However, the role of zonulin as a promoting factor of intestinal barrier disruption in patients with liver cirrhosis has not been studiedadequately. We evaluated serum zonulin levels in patients with different stages of advanced liver disease. According to our findings, serum zonulin levels are increased in patients with more advanced liver disease and are independently associated with progression to decompensation.
