A New Model for Predicting Venesection Therapy Requirements in Hereditary Hemochromatosis Using Non-Invasive Liver Iron Concentration Measurement.
Authors: St. Pierre Timothy G. , Jeffrey Gary P. , Rossi Enrico , Fleming Adam J. , Chua-anusorn Wanida , Clark Paul R. , Olynyk John K. 
Published: October 2019

Newly diagnosed hereditary hemochromatosis subjects are treated with venesection therapy in order to reduce body iron stores. Liver iron concentration (LIC) is the most reliable indicator of body iron stores. Proton transverse relaxation rate imaging (FerriScan®) enables a highly specific and sensitive measurement of LIC [St. Pierre TG, Clark PR, Chuaanusorn W, Fleming A, Jeffrey GP, Olynyk JK, Pootrakul P, Robins E, Lindeman R. Blood105 (2005) 855–861]. In this study FerriScan® was used to follow the LIC and liver volume in 7 newly diagnosed homozygous C282Y hereditary hemochromatosis patients. Baseline LIC values ranged from 3.4 to 16.7 mg Fe/g dry tissue. The total number of venesected units of blood required to lower the LIC of each subject to the upper end of the normal range was initially estimated from body mass and LIC [Angelucci, E., Brittenham, G.M., McLaren, C.E. et al. (2000) New Eng. J. Med.343, 327–331]. The LIC of each subject was measured again after approximately half the estimated total number of units of blood had been removed, and a third time near completion of the venesection therapy. For each subject, a straight line was fitted to the LIC versus venesected blood volume data. The coefficient of variation of the differences between the measured LIC values and the fitted lines (a measure of the precision of the LIC measurements) was found to be 7 %. Total body iron stores were measured by extrapolating the straight line fit through the LIC vs venesected blood volume to zero LIC and using a value of 0.473 mg Fe/mL for the blood iron concentration. Total liver iron content was determined by simultaneous measurement of LIC and liver volume with MRI. The data indicated that the higher the LIC at diagnosis, the higher was the fraction, α, of the total body iron store located in the liver. Hence a linear model relating α to LIC is proposed, α = β x LIC + α0. Linear regression was used on the 21 measurements of LIC in the study to find the following optimum model parameters α0 = 0.169 and β = 0.0274 g wet liver/mg Fe. Using these parameters the total blood volume (TBV) to be removed from a patient to bring the LIC down from an initial value (LICi) to a target value (LICf) can be calculated using TBV = [(LICi – LICf) x V]/(β x LICi + α0) where V is the liver volume. Using the 21 measurements in this study a straight line relationship between measured and predicted numbers of units of blood to bring LIC to 1 mg Fe/g dry tissue was found to have slope 0.99 and Pearson’s correlation coefficient of 0.97. The data suggest that simultaneous measurement of LIC and liver volume with MRI (data acquisition time less than 30 minutes) can be used to predict venesection requirements in hereditary hemochromatosis. The measurement of baseline LIC also enables an estimate of the possible visceral or metabolic consequences of the iron burden. For example, in the absence of other complicating factors, a measurement of the LIC multiplied by the age of the subject gives a good predictor of iron induced liver damage [Olynyk, J.K, St. Pierre, T.G., Britton, R.S., Brunt, E.M., and Bacon, B.R. (2005) Am. J. Gastro., 100, 837–841].