2012 Position Statement on MRI-Based Hepatic Iron Assessment Methods
May 31, 2012 – The Cooley’s Anemia Foundation strongly supports the consensus recommendations of the Thalassemia Clinical Research Network (TCRN) to obtain at least annual MRI for hepatic iron and cardiac iron T2* MRI beginning at age 10 years (with more frequent measurements considered for patients with cardiac T2* <10-20 ms) and an annual liver iron measurement, without a specified starting age, for transfusion-dependent patients and to adjust chelation in response to these measurements. We recommend that hepatic MRI methods be available to patients with thalassemia and other iron overload disorders.
The Cooley’s Anemia Foundation is dedicated to serving people afflicted with various forms of thalassemia, most notably the major form of this genetic blood disorder, Cooley’s anemia (also known as thalassemia major). Our mission is to advance the treatment and cure for this serious blood disorder, enhancing the quality of life of patients and educating the medical profession, trait carriers and the public about thalassemia major. The Cooley’s Anemia Foundation supports research and medical advancements for patients and their families. To this end, the Foundation supports the use of MRI methods, as important, patient-friendly alternatives to liver biopsy.
MRI iron assessment methods provide a non-invasive, cost-effective means to monitor liver iron concentration in transfused patients with thalassemia. FerriScan® R2 is an FDA approved, MRI-based proprietary data analysis method capable of accurately measuring liver iron concentrations in patients regardless of the amount of iron in their liver, a feature particularly important for thalassemia patients with heavy iron loading. MRI image data are acquired on a local scanner and electronically transmitted to a central data analysis center that is ISO 13485 certified.
Traditional techniques for monitoring the body iron burden include serum ferritin and liver biopsy. Serum ferritin provides useful trending information; however, it is an unreliable indicator of the magnitude of iron overload as results can be confounded by inflammation, infection or other underlying diseases.
Liver biopsy has traditionally been regarded as the gold standard for assessing iron overload and published data confirm that liver iron is closely correlated with total body iron stores. However, a liver biopsy is invasive, can be painful and carries the risk of complications. Furthermore, since iron is deposited in the liver in a non-uniform manner, the small amount of liver tissue obtained from a liver biopsy may not be representative of the entire liver, often making this technique inaccurate. Liver biopsies are substantially more expensive than R2-MRI.
MRI iron assessment has several advantages over liver biopsy including:
- Non-invasive: therefore, not painful or harmful to the patient.
- Provides a measurement of the amount of iron across a large cross-section of the liver.
- It is a more direct measure than serum ferritin.
When MRI is employed to measure liver iron concentrations, it helps physicians:
- Determine if and when chelation therapy should begin.
- Monitor how the chelation therapy is working.
- Adjust therapy accordingly.
- Provide accurate feedback to the patient to assist with potential compliance issues.
A total of 44 clinical papers (list available upon request) have been published since 2005, showing the clinical benefits of this technology in measuring and monitoring LIC as part of ongoing clinical management. In January 2012, a report from the Thalassemia Longitudinal Cohort study was published on chelation use and iron burden in North American and British thalassemia patients (Kwiatkowski et al. Blood 2012). This 10-year study of 327 patients resulted in the following key findings related to the use of non-invasive MRI measures for LIC:
- MRI techniques have nearly replaced liver biopsy for the measure of liver iron concentration (LIC);
- Between 2002-2011, there was a significant increase in the number of patients who had LIC measures by MRI and a sharp decline in the use of liver biopsy;
- MRI: 11.9% during 2002-2004 to 77.9% during 2007-2009 and 85.2% in 2009-2011;
- Liver Biopsy: Declined from 65.6% in 2002-2004 to 9.3% in 2007-2009 and 1.8% in 2009-2011.
There was a significant improvement in iron loading over time, as judged by MRI but not by serum ferritin;
- 62% of patients had an improvement in cardiac T2*;
- No change was seen in serum ferritin measurements over the same time period.
Liver MRI was generally more acceptable to patients, permitting more frequent monitoring, if required.
The authors represent many of the nation’s leading Thalassemia Treatment Centers and concluded:
The results of the study strongly support the routine use of MRI measurements for LIC and oral chelation in the management of iron overload.
The lack of significant change in serum ferritin levels underscores the need for LIC assessment using MRI in patients with thalassemia.
The use of MRI, with appropriate treatment adjustments, may decrease morbidity and mortality over time.
The authors recommend at least annual liver iron measurements, without a specified starting age, for transfusion-dependent patients and to adjust chelation in response to these measurements.
The Cooley’s Anemia Foundation believes that MRI iron assessments should be available to all patients who rely on iron overload measures to identify excess iron which accumulates in the liver and which leads to serious complications such as liver fibrosis and organ failure. Regular monitoring of liver iron can improve the management of iron overload leading to prolonged and improved quality of life.
Based on our review of the peer-reviewed literature, Cooley’s Anemia Foundation recommends that third party insurance companies develop positive coverage policies so that consumers can access this test, providing more accurate and cost-effective results than liver biopsy.