P1561: is iron overload associated with worse outcomes in patients with chronic liver disease undergoing liver transplant?

Background: Iron overload (IO) is found in up to 78% of patients with chronic liver disease (CLD), secondary to local iron deposits and hepcidin dysregulation. An increase in infections and non-relapse related mortality has been reported in patients with IO who underwent hematopoietic cell transplantation (HCT). The effect of IO in patients without hereditary hemochromatosis (HH) who underwent liver transplant (LT) is unknown. Aims: To determine the clinical impact of IO in patients who underwent LT in a tertiary referral center. Methods: Retrospective cohort study that included patients who underwent LT from 2015 to 2017 at the Instituto Nacional de Nutricion (INCMNSZ), excluding those with HH. Explant liver biopsies were analyzed by two pathologists, using Perls Prussian blue stain to detect iron deposits in hepatocytes, sinusoids, and portal areas. The sum of this achieved the total iron score (TIS), divided by age in order to obtain the histochemical hepatic iron index (HHII), considering a score ≥ 0.15 as IO. Group comparisons were made with Pearson chi-square and Mann-Whitney U test, a logistic regression was used to analyze factors associated with IO, and survival was analyzed with the log-rank test. Results: A hundred and five patients were included. Kappa index between pathologists was 0.923 (IC 95% 0.849 – 0.997). Forty-seven patients had IO (44.7%), predominantly men (57.4%). Divided by etiology, IO was more frequent with viral (62.5%) and metabolic (53.6%) etiologies, compared to autoimmune and other causes (p=0.012). A multivariate analysis concluded that obesity (OR 4.35, IC 95% 1.52 – 12.45, p = 0.006) and alcohol consumption (OR 6.68, IC 95% 2.15 – 20.82, p=0.001) were associated with IO (w/IO). Median saturation index and ferritin were higher in patients w/IO, 47% (interquartile range (IQR) 74 – 84%) vs 25% (IQR 19 – 53%) without IO (w/o IO), and 347 ng/mL vs 61.2 ng/mL, respectively (both, p<0.001). Compared to liver biopsy, serum iron tests (SIT) had a sensitivity of 72.2% and a specificity of 87.1%. Regarding early (< 90 days) complications post LT, a trend towards a higher rate of complications was found in patients with IO (91.5 vs 77.6%, p=0.07), mainly due to metabolic complications (68.1 vs 46.6%, p=0.344). We found no difference in the patient’s length of stay or in intensive care unit stay, nor in infections, rejection or rehospitalization rates (Figure 1). Median follow-up was 61.5 months (IQR 49.7 – 72.9 months). All deaths occurred during the first 60 days, with an overall survival (OS) at 60 days of 92.4%, 97.9% in patients w/IO vs 87.9% w/o IO (p=0.006). Relapse occurred in 25.7% of the patients, 31.9% in the group w/IO and 20.7% w/o IO (p=0.26). Four-year disease-free survival (DFS) was 66.7% in patients w/IO vs 75.7% w/o IO (p=0.26). Image:Summary/Conclusion: IO is frequent in patients with CLD, particularly in patients with viral and metabolic etiologies, and is associated with obesity and alcohol consumption. SIT had a specificity of 87.1% to exclude IO in patients with CLD. A trend towards a higher rate of metabolic complications was found, with a statistically significant higher OS rate at 60 days. No difference was found in relapse rate or DFS. Contrary to what has been described in other scenarios, in our cohort, IO was not associated with worse outcomes.