Cappellini and colleagues1  claim that the use of a superconducting quantum interference device (SQUID) biosusceptometer underestimates liver iron concentration (LIC) in their phase 3 study of deferasirox (DFX). LIC was measured either in deparaffinized liver samples excised by various biopsy techniques (Menghini with saline flushing, cutting needles) or in an anterior position above the right liver lobe by biomagnetic liver susceptometry (BLS) using low TC-SQUID biosusceptometers. In vivo wet-weight LICs measured by BLS were converted by a factor of 3.33 into dry-weight values. This approximate conversion factor2  has been uncritically adopted throughout the literature, even by ourselves, although there were strong data available supporting a higher factor for the ratio of wet to dry weight3,4  and a significant difference between LIC from fresh tissue and from deparaffinized samples.5,6  Thus, the conversion factor between LIC as determined by BLS and from deparaffinized liver samples would have been at least 5.5 ± 1.0 (calculated factor ± uncertainty).7  Related to activities around this phase 3 study program of DFX, the authors have developed more direct knowledge of ratios of wet to dry weight by various biopsy processing techniques (eg, a conversion factor of 5.8 ± 0.6 for deparaffinized liver samples) and their “paramount importance” for comparison of LICs.8 

Consequently, the authors should have corrected their LICs measured by SQUID-BLS in order to analyze their data more accurately in this important publication on a novel oral chelator. We think that it is allowed to correct an initially false study assumption in a scientific paper. Measurements by BLS would have the highest impact especially in the LIC group of 7 mg Fe/g dry weight or less, although the final outcome may not change significantly. Moreover, we would hope to avoid giving potential readers the wrong impression that BLS underestimates LIC per se. One could, in fact, claim the opposite, as in our title, particularly in the case of deparaffinized samples.

As part of this discussion, it should be emphasized that the different conversion factors also have a strong impact on the LIC safety thresholds in iron-overloaded patients with thalassemia. These recommended thresholds were based in part on LICs measured by BLS with an approximate conversion factor of 3.33. For example, the threshold for increased risk of cardiac failure of LICs equaling 80 μmol/g wet weight (about 15 mg/g dry weight)1(p 3455) would convert to 26 ± 5 mg/g dry weight using the conversion factor of 5.8 for deparaffinized liver biopsies. Thus, dry-weight LICs could be very different depending on the selected biopsy techniques and processing methods.7 

1
Cappellini MD, Cohen A, Piga A, et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with β-thalassemia.
Blood
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2006
;
107
:
3455
-3462. (Prepublished online
December
13
, 2005, as DOI .)
2
Olivieri NF, Brittenham GM. Iron-chelating therapy and the treatment of thalassemia.
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Brink B, Disler P, Lynch S, Jacobs P, Charlton R, Bothwell T. Patterns of iron storage in dietary iron overload and idiopathic hemochromatosis.
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4
Zuyderhoudt FMJ, Hengeveld P, Van Gool J, Jörning GGA. A method for measurement of liver iron fractions in needle biopsy specimens and some results in acute liver disease.
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Beilby J, Prins A, Swanson N. Determination of hepatic iron concentration in fresh and paraffin-embedded tissue.
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6
Butensky E, Fischer R, Hudes M, et al. Variability in hepatic iron concentration from percutaneous needle biopsy specimens in patients with transfusional hemosiderosis.
Am J Clin Path
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2005
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7
Fischer R, Piga A, Harmatz P, Nielsen P. Monitoring long-term efficacy of iron chelation treatment with biomagnetic liver susceptometry.
Ann NY Acad Sci
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2005
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8
Ropert-Bouchet M, Turlin B, Graham G, et al. Drying methods affect the wet: dry ratio of liver tissue samples and impact liver iron content (LIC) measurements.
Paper presented at BioIron 2005
.
May
25
,
2005
. Prague, Czech Republic.