Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2020; 26(16): 1938-1949
Published online Apr 28, 2020. doi: 10.3748/wjg.v26.i16.1938
Iron metabolism imbalance at the time of listing increases overall and infectious mortality after liver transplantation
Elodie Fallet, Michel Rayar, Amandine Landrieux, Christophe Camus, Pauline Houssel-Debry, Caroline Jezequel, Ludivine Legros, Thomas Uguen, Martine Ropert-Bouchet, Karim Boudjema, Dominique Guyader, Edouard Bardou-Jacquet
Elodie Fallet, Amandine Landrieux, Pauline Houssel-Debry, Caroline Jezequel, Ludivine Legros, Thomas Uguen, Dominique Guyader, Edouard Bardou-Jacquet, Service des Maladies du Foie, CHU Rennes, University Rennes, Rennes 35033, France
Michel Rayar, Pauline Houssel-Debry, Karim Boudjema, Service de Chirurgie Hepatobilaire, CHU Rennes, University Rennes, Rennes 35033, France
Christophe Camus, Service de Réanimation médicale, CHU Rennes, University Rennes, Rennes 35033, France
Martine Ropert-Bouchet, Laboratoire de biochimie, CHU Rennes, University Rennes, Rennes 35033, France
Author contributions: Bardou-Jacquet E contributed to study design and supervision; Fallet E and Bardou-Jacquet E drafted the manuscript; Fallet E, Uguen T and Rayar M gathered the Data; Bardou-Jacquet E and Rayar M performed statistical analysis; Landrieux A, Camus C, Houssel-Debry P, Jezequel C and Legros L managed the patients; all authors critically revised the manuscript.
Institutional review board statement: This study was approved by the Rennes University Ethics Committee on the 20th of October 2015.
Informed consent statement: According to this law (Loi Jardé n° 2012-300 the 5th of March 2012) the retrospective use of clinical and biological data generated during the routine car of patient does not require signed informed consent for patients included in this kind of study.
Conflict-of-interest statement: Authors have no conflict of interest to declare.
Data sharing statement: No additional data are available.
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:
Corresponding author: Edouard Bardou-Jacquet, MD, PhD, Professor of Medicine, Service des Maladies du Foie, CHU Rennes, University Rennes, CIC1414, Rennes 35033, France.
Received: December 30, 2019
Peer-review started: December 30, 2019
First decision: January 19, 2020
Revised: March 30, 2020
Accepted: April 17, 2020
Article in press: April 17, 2020
Published online: April 28, 2020

Liver transplantation (LT) is the best treatment for patients with liver cancer or end stage cirrhosis, but it is still associated with a significant mortality. Therefore identifying factors associated with mortality could help improve patient management. The impact of iron metabolism, which could be a relevant therapeutic target, yield discrepant results in this setting. Previous studies suggest that increased serum ferritin is associated with higher mortality. Surprisingly iron deficiency which is a well described risk factor in critically ill patients has not been considered.


To assess the impact of pre-transplant iron metabolism parameters on post-transplant survival.


From 2001 to 2011, 553 patients who underwent LT with iron metabolism parameters available at LT evaluation were included. Data were prospectively recorded at the time of evaluation and at the time of LT regarding donor and recipient. Serum ferritin (SF) and transferrin saturation (TS) were studied as continuous and categorical variable. Cox regression analysis was used to determine mortality risks factors. Follow-up data were obtained from the local and national database regarding causes of death.


At the end of a 95-mo median follow-up, 196 patients were dead, 38 of them because of infections. In multivariate analysis, overall mortality was significantly associated with TS > 75% [HR: 1.73 (1.14; 2.63)], SF < 100 µg/L [HR: 1.62 (1.12; 2.35)], hepatocellular carcinoma [HR: 1.58 (1.15; 2.26)], estimated glomerular filtration rate (CKD EPI Cystatin C) [HR: 0.99 (0.98; 0.99)], and packed red blood cell transfusion [HR: 1.05 (1.03; 1.08)]. Kaplan Meier curves show that patients with low SF (< 100 µg/L) or high SF (> 400 µg/L) have lower survival rates at 36 mo than patients with normal SF (P = 0.008 and P = 0.016 respectively). Patients with TS higher than 75% had higher mortality at 12 mo (91.4% ± 1.4% vs 84.6% ± 3.1%, P = 0.039). TS > 75% was significantly associated with infection related death [HR: 3.06 (1.13; 8.23)].


Our results show that iron metabolism imbalance (either deficiency or overload) is associated with post-transplant overall and infectious mortality. Impact of iron supplementation or depletion should be assessed in prospective study.

Keywords: Iron deficiency, Overload, Cirrhosis, Infection, Death, Ferritin, Transferrin saturation

Core tip: Iron is an essential element for many biological functions. Its deficiency or overload is associated with poor outcomes in many settings. Few data are available in patients undergoing liver transplantation, and more specifically on infection related deaths. Our study is the first to describe in a large number of patients, the impact or iron metabolism imbalance on mortality after liver transplantation. Our results show that both iron deficiency and overload are significantly associated with increased mortality. Further we show that transferrin saturation higher than 75% is associated with mortality.