Increased Liver Iron Concentration (LIC) in Adults with Non-Transfusion Dependent Sickle Cell Disease (NTD-SCD): Correlation with Serum Ferritin Concentrations

Introduction:

Hepatic iron concentration (HIC) is used as a surrogate for total iron balance to guide chelation therapy in transfusion-dependent and independent patients. Unfortunately, liver biopsy is invasive and provides only indirect information regarding other organ systems. FerriScanprovides an accurate validated measurement of liver iron concentration (LIC) through a non-invasive, using patented R2-MRI imaging technology.

Aim:

To determine the iron status of 11 patients with non-transfusion dependent (NT) patients with sickle cell disease (SCD).

Patients and methods:

FerriScan (a quick, easy and painless, with an MRI scan time of only two minutes) is used to determine LIC in eleven adults with NT-SCD. Serum ferritin, iron concentrations and hepatic enzymes (ALT and AST) concentrations and total iron binding capacity (TIBC) were measured.

Results:

11 adults with NT-SCD were studied. Three had serum ferritin > 500 umol/L , 2 out of the three (ferritin level 1138 and 531 ug/L) had high liver iron measured by ferriScan (> 30 mmol/kg dry tissue). One patient had high liver iron content despite a concomitant serum ferritin concentration = 237 ug/L. On the other hand a patient had serum ferritin = 1117 ug/L while his liver iron was still (27 mmol/kg dry tissue) in the normal range. Serum ferritin concentrations were correlated significantly with liver iron content measured by ferriScan (r = 0.47, p = 0.05). (fig) Three patients had elevated liver enzymes (ALT and AST). Neither serum ferritin, nor LIC was correlated significantly with hepatic function.

Discussion:

In this study significant number of patients with ND-SCD had high LIC and high serum ferritin and hepatic enzymes (ALT and AST). Elevated levels of LIC and ferritin impose high risk for hepatic disease and cardiac toxicity in these patients. Evidence suggests that patients with high LIC have higher risk of liver fibrosis and cirrhosis as a result of iron overload. In addition, Liver iron concentration (LIC) over 15.0 mg Fe/g dry weight is associated with increased risk of cardiac diseases. Moreover, the liver is considered the early warning system against later endocrine complications, due to iron overload. For NT-SCD, with increased LIC, effective management of liver iron concentration is critical to ensure risk of morbidity due to iron overload is minimized

Summary: This is the first study that document increased iron overload in NT-SCD patients. Therefore, we recommend measuring serum ferritin and LIC in NT-SCD patients. Those with increased LIC and/or ferritin should be chelated to prevent long term complications of iron overload.