Published online Apr 28, 2020. doi: 10.3748/wjg.v26.i16.1938
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.
Iron metabolism could be easily corrected before liver transplantation, thus assessing its impact on mortality is crtitical before designing clinical trials in that purpose.
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.
Retrospective cohort analysis with Cox multivariate Regression. Survival was also estimated though Kaplan Meier analysis.
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)].
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.
A prospective randomized clinical trial is required to assess the beneficial effect of correction iron metabolism imbalance before liver transplantation.