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
ARTICLE HIGHLIGHTS
Research background
Gut permeability is distorted in patients with liver cirrhosis and the observed deregulation of the intestinal integrity plays a crucial role in the development of bacterial translocation. Bacterial translocation contributes to the occurrence or aggravation of serious complications in patients with liver cirrhosis. Zonulin is a recently recognized protein, synthesized by the intestinal and liver cells, and thought to play an important role in the regulation of tight junctions between intestinal cells.
Research motivation
Increased zonulin levels have been observed in such diseases as celiac disease and inflammatory bowel disease and have shown correlation to the impairment of intestinal permeability. The exact mechanism that leads to the deregulation of the intestinal integrity in liver cirrhosis is not thoroughly investigated. Zonulin may have a role in the observed alterations of the gut barrier in advanced chronic liver disease.
Research objectives
We aimed to investigate if serum zonulin levels are altered in patients with different stages of liver cirrhosis and investigate their possible impact on patients’ prognosis.
Research methods
We included 116 cirrhotic patients who attended our outpatient clinic during a 12-mo period. Serum zonulin levels were measured, as were epidemiological, laboratory and clinical data, and data from elastography and ultrasonography at baseline. Sixty-three patients were followed up for at least 1year and data from clinical events (death, liver transplantation and liver disease decompensation) were collected.
Research results
Our study included mainly Child-Turcotte-Pugh (CTP)-A (67%) and CTP-B patients (28%). We observed that serum zonulin levels are increased in patients with more advanced liver disease, such as patients with CTP–B stage, patients with ascites, or those with history of hepatic encephalopathy. What is more, serum zonulin levels were independently associated with the probability of decompensation within the next year.
Research conclusions
According to our study results, serum zonulin levels are increased in patients with advanced chronic liver disease. What is more, a new agent, zonulin, is found to be implicated in the progress towards advanced liver disease.
Research perspectives
Our findings highlight once more the significance of gut barrier deregulation in the setting of liver cirrhosis and emphasize the need of further studies in the field, aiming to reveal the complex pathophysiological interplay which leads to bacterial translocation. Especially, the role of zonulin should be further investigated, due to its possible therapeutic implications, as a zonulin antagonist alreadyexists and is being tested in studies of celiac disease.
