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Finding Solutions on A Global Scale
CHORI Researchers Apply New Technology to Measure Liver Iron Concentrations
A new collaborative international study with University of California, San Francisco, the University of Cairo, Egypt, and CHORI provides hopeful news for thousands of patients who suffer from iron overload across the globe. The study, published in the Journal of Clinical Densitometry, investigated the potential for a new and affordable technology, dual-energy x-ray absorptiometry (DXA) to accurately monitor iron status, potentially paving the way to providing more accurate liver iron concentration (LIC) measurements in developing nations.

“For thalassemia and sickle cell disease patients to be at their optimal health while being treated with chronic blood transfusions requires quite a beautiful balance between iron overload, chelation treatment to remove the iron, and anemia,” says CHORI scientist and first author, Ellen Fung, PhD.

“The only way to negotiate the optimal balance is for us to be able to accurately and affordably measure liver iron con-
centration.”

Iron overload is a major issue for patients with blood disorders. While blood transfusions provide the necessary oxygen flow to all the body's tissues, transfusions also cause a build-up of excess iron that can be toxic to the liver, heart and other organs. A variety of chelator medications to remove that iron are available worldwide, but inexpensive methods to accurately determine how much chelation treatment is required, are not.

"The gold standard in assessing liver iron concentration, or LIC, is the SQUID, a superconducting quantum interference devise," says Dr. Fung.
“The SQUID is completely non-invasive and extremely accurate. But right now, our research institute has one of only three SQUIDs in the world.”
Magnetic resonance imaging (MRI) is a more widely available method, but just as expensive as the SQUID. This leaves only liver biopsy or measuring serum ferritin levels the protein that stores and releases iron in the body – both of which come with their own problems.

"Liver biopsy is quite invasive for patients, so not a good option for frequent LIC measurements," explains Dr. Fung. "Serum ferritin is cheap and available, but is a notoriously poor way of determining a patient's iron status because it can be influenced by many other things besides excess body iron."

As a result, Dr. Fung and her colleagues wanted to determine whether or not the DXA, a technology used for assessing bone status, might provide a cheap and accessible alternative for LIC measurements, especially in less developed nations where sickle cell disease and thalassemia are much more common.
"Right now, most of these countries have access to iron chelators. What they need to properly manage chelator use however, is a way to effectively measure iron status," says Dr. Fung. "We have many patients that have really low ferritin levels but still have very high iron concentrations. In such situations, if ferritin is your only measure, you could be doing these patients a great disservice."

Dr. Fung and her colleagues selected the DXA as a potential solution for three specific reasons: it is affordable; it is becoming a standardized tool worldwide, and particularly in developing countries, to measure bone health; and it requires very little technical training to use.

"DXA measures bone density, but it also measures tissue density. Lean mass is denser than fat for example, and bone mass is denser than lean mass," Dr. Fung explains.
"When we look at tissue around the liver, iron in the tissue shows up as having more density. And it turns out that that density level correlates with overall iron concentration."

In fact, the results of the study showed that when the DXA measurements were used in combination with ferritin measurements, the accuracy of the measurement improved from 38 percent with ferritin alone, to 61 percent accurate when combined with DXA readings.

Although Dr. Fung acknowledges that 61 percent isn't perfect, the DXA nearly doubles the accuracy of ferritin alone, laying the foundation for DXA to provide an essential and missing link in LIC measurements.

"The data is only preliminary and more study is always needed," says Dr. Fung.

“Never-the-less, our results suggest that DXA could provide a critical tool to improve the non-invasive assessment of iron overload in geographies that have limited access to more expensive options.”

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Tuesday, May 17, 2011 8:19 AM

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