Meta-Analysis
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jul 27, 2020; 12(7): 389-398
Published online Jul 27, 2020. doi: 10.4254/wjh.v12.i7.389
Effect of zinc treatment on clinical outcomes in patients with liver cirrhosis: A systematic review and meta-analysis
Huey K Tan, Adam Streeter, Matthew E Cramp, Ashwin D Dhanda
Huey K Tan, Matthew E Cramp, Ashwin D Dhanda, South West Liver Unit, University Hospitals Plymouth NHS Trust, Plymouth PL6 8DH, United Kingdom
Huey K Tan, Matthew E Cramp, Ashwin D Dhanda, Hepatology Research Group, Institute of Translational and Stratified Medicine, Faculty of Health, University of Plymouth, Plymouth PL6 8BU, United Kingdom
Adam Streeter, Medical Statistics Group, Faculty of Health, University of Plymouth, Plymouth PL6 8BU, United Kingdom
Author contributions: Dhanda AD conceived the study. Tan HK, Dhanda AD and Cramp ME performed the research. Streeter A analysed the data; Tan HK wrote the manuscript. Dhanda AD and Cramp ME supervised the paper; all authors read and approved the final manuscript.
Conflict-of-interest statement: None of the authors have any relevant conflict of interest to declare.
PRISMA 2009 Checklist statement: The authors confirm that the manuscript was prepared and revised according to the PRISMA 2009 Checklist for this meta-analysis.
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: Ashwin D Dhanda, BSc, MBChB, MRCP, PhD, Associate Professor, Consultant and Honorary Associate Professor in Hepatology, Hepatology Research Group, Institute of Translational and Stratified Medicine, Faculty of Health, University of Plymouth, John Bull Building, Research Way, Plymouth PL6 8BU, United Kingdom. ashwin.dhanda@plymouth.ac.uk
Received: March 30, 2020
Peer-review started: March 30, 2020
First decision: April 22, 2020
Revised: June 4, 2020
Accepted: June 10, 2020
Article in press: June 10, 2020
Published online: July 27, 2020
Abstract
BACKGROUND

Zinc is an essential trace element integral to many cellular and immune functions. Zinc deficiency is highly prevalent in patients with cirrhosis and related to disease severity.

AIM

To evaluate whether zinc supplementation improves clinical outcomes (disease severity and mortality) in patients with cirrhosis.

METHODS

This prospectively registered systematic review (PROSPERO reference: CRD42018118219) included all studies in Medline, Embase or Cochrane database with inclusion criteria of adult human studies, comparing zinc supplementation of at least 28 d with standard care or placebo in patients with cirrhosis. Mortality and clinical severity score data were extracted. Random effects meta-analyses compared mortality at 6 mo and 2 years. Risk of bias was assessed using the National Institutes of Health quality assessment tool.

RESULTS

Seven hundred and twelve articles were identified of which four were eligible. Zinc formulations and doses varied (elemental zinc 3.4-214 mg daily) for different intervention periods in patients with differing etiology and severity of cirrhosis. Two studies were considered to be at high risk of bias. There was no significant difference in 6-mo mortality between patients treated with zinc versus controls [risk ratio 0.98 (0.90-1.05)]. Changes in severity scores were not reported in any study.

CONCLUSION

Zinc supplementation is not associated with reduced mortality in patients with cirrhosis. Findings are limited by the small number of eligible studies and significant heterogeneity in intervention and patient population.

Keywords: Zinc, Cirrhosis, Mortality

Core tip: Zinc deficiency is highly prevalent in patients with cirrhosis and may contribute to disease progression and mortality. This systematic review aimed to determine whether zinc supplementation was associated with clinical outcomes in patients with cirrhosis. Meta-analysis of data from four eligible studies found that zinc supplementation was not associated with reduced mortality at 6 mo. No study reported changes in disease severity or complications. Eligible studies were highly heterogeneous with different zinc formulations, dosage and duration applied to varying patient populations. Further well-designed prospective studies are required to determine whether zinc supplementation improves long-term clinical outcome in patients with cirrhosis.