Correlation of Serum Ferritin Levels with Liver Iron Concentration By MRI Measurement in Sickle Cell Patients with Transfusional Iron Overload
Authors: Ajebo Germame , Mangaonkar Abhishek A. , Ahmad Imran , Barrett Nadine , Wells Leigh , Patel Niren , Xu Hongyan , Kutlar Abdullah 
Published: October 2019

Abstract
Background:
Recent reports from the thalassemia literature suggest that serum ferritin may be a poor and possibly misleading measure of total iron store in heavily iron overloaded patients. Moreover, the relationship between plasma ferritin and body iron stores is distorted by ascorbate deficiency, fever, infection, inflammation, and hepatic dysfunction, all of which occur in patients with sickle cell disease (SCD). On the other hand, following the results of multiple studies that demonstrated a high correlation of hepatic iron overload determination by magnetic resonance imaging to the values found in specimens from liver biopsy, R2* liver MRI has emerged as the best noninvasive yet highly sensitive and specific method for measuring the level of iron in the liver.
The goal of this study was to determine the correlation of liver iron by liver R2* MRI with serum ferritin and by extrapolation assess whether serum ferritin remains to be a useful clinical marker of iron overload in patients with SCD. We also sought to determine the correlation of liver iron concentration with abnormalities in the liver function tests.
Methods:
We conducted a retrospective analysis of 31 patients with sickle cell disease and transfusional iron overload who are being followed at the Augusta University Comprehensive Sickle Cell Center. Serum ferritin, hepatic R2* MRI liver iron concentration, hepcidin level, and liver function tests (AST, ALT and total bilirubin) were assessed for correlation. We used the Pearson correlation coefficient to determine the relationship between the various variables with hepatic R2* MRI.
Results:
Serum ferritin levels showed a statistically significant positive correlation with R2* hepatic MRI (r = 0.479 with p = 0.0085) in the patients with SCD and transfusional iron overload . We also saw a positive correlation, although not statistically significant, between hepcidin level and liver iron concentration by liver MRI(r=0.493 with P= 0.399). This may be due to the small sample size of the patients who had hepcidin levels available.
On the other hand, no correlation was detected between abnormalities in liver function tests and liver iron concentration. The correlation between liver iron concentration(LIC) and AST was 0.045 with p = 0.816 and the correlation between LIC and ALT was 0.233 with p = 0.224.
Conclusion:
While R2* MRI is the the most accurate method to diagnose and monitor response to therapy in SCD patients with transfusional iron overload, we have found a statistically significant positive correlation with serum ferritin values. Thus, where R2* liver MRI is unavailable, serum ferritin remains a clinically useful tool that can be used in the diagnosis and monitoring of iron overload in sickle cell patients, despite its limitations.
As previously reported, we did not find any correlation between LIC and liver function abnormalities in this population (Harmatz et al, 2000) These findings suggest that patients with SCD may have a different response to iron overload in comparison to patients with thalassemia or hereditary hemochromatosis.

Disclosures
Kutlar: Bluebird Bio: Other: DSMB Member; Sancilio: Other: DSMB Chair; Novartis: Consultancy, Honoraria, Other: Personal fees, Research Funding.