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
Research background

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.

Research motivation

Iron metabolism could be easily corrected before liver transplantation, thus assessing its impact on mortality is crtitical before designing clinical trials in that purpose.

Research objectives

The main objectives, the objectives that were realized, and the significance of realizing these objectives for future research in this field should be described in detail.

Research methods

Retrospective cohort analysis with Cox multivariate Regression. Survival was also estimated though Kaplan Meier analysis.

Research results

A large number of patients was studied (553) and followed for 95 mo. At the end of follow-up 196 patients were dead, 38 of them because of infections. In multivariate analysis, overall mortality was significantly associated with transferrin saturation (TS) higher than 75% [HR: 1.73 (1.14; 2.63)], serum ferritin lower than 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 serum ferritin (< 100 µg/L) or high serum ferritin (> 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). Moreover TS higher than 75% was significantly associated with infection related death [HR: 3.06 (1.13; 8.23)].

Research conclusions

Our study is the first to describe the respective impact of iron deficiency in patient undergoing liver transplantation. This suggests that active management of iron deficiency with iron supplementation before liver transplantation could significantly improves outcome after liver transplantation. Further this is the first study showing that high TS is associated with higher short term mortality. This suggests that exposure to toxic forms of iron increase cellular damages in the perioperative period and that treating iron overload before liver transplantation could improves outcome.

Research perspectives

A prospective randomized clinical trial is required to assess the beneficial effect of correction iron metabolism imbalance before liver transplantation.