- •Non-invasive and sensitive detection of hepatocellular iron overload.
- •Performance comparable to AAS and MRI.
- •Promising cost-effective tool for liver iron screening.
- •Follow-up of hepatic iron after phlebotomy.
- •Detection of hepatic iron overload in metabolic liver diseases.
Background & Aims
Liver iron accumulates in various chronic liver diseases where it is an independent factor for survival and carcinogenesis. We tested a novel room-temperature susceptometer (RTS) to non-invasively assess liver iron concentration (LIC).
Two hundred and sixty-four patients with or without signs of iron overload or liver disease were prospectively enrolled. Thirty-five patients underwent liver biopsy with semiquantitative iron determination (Prussian Blue staining), atomic absorption spectroscopy (AAS, n = 33), or magnetic resonance imaging (MRI, n = 15).
In vitro studies demonstrated a highly linear (r2 = 0.998) association between RTS-signal and iron concentration, with a detection limit of 0.3 mM. Using an optimized algorithm, accounting for the skin-to-liver capsule distance, valid measurements could be obtained in 84% of cases. LIC-RTS showed a significant correlation with LIC-AAS (r = 0.74, p <0.001), LIC-MRI (r = 0.64, p <0.001) and hepatocellular iron (r = 0.58, p <0.01), but not with macrophage iron (r = 0.32, p = 0.30). Normal LIC-RTS was 1.4 mg/g dry weight. Besides hereditary and transfusional iron overload, LIC-RTS was also significantly elevated in patients with alcoholic liver disease. The areas under the receiver operating characteristic curve (AUROC) for grade 1, 2 and 3 hepatocellular iron overload were 0.72, 0.89 and 0.97, respectively, with cut-off values of 2.0, 4.0 and 5.0 mg/g dry weight. Notably, the positive and negative predictive values, sensitivity, specificity and accuracy of severe hepatic iron overload (HIO) (grade ≥2) detection, were equal to AAS and superior to all serum iron markers. Depletion of hepatic iron could be efficiently monitored upon phlebotomy.
RTS allows for the rapid and non-invasive measurement of LIC. In comparison to MRI, it could be a cost-effective bedside method for LIC screening.
Lay summary: Novel room-temperature susceptometer (RTS) allows for the rapid, sensitive, and non-invasive measurement of liver iron concentration. In comparison to MRI, it could be a cost-effective bedside method for liver iron concentration screening.
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- Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases.Hepatology. 2011; 2011: 328-343
- Liver EAFTSOT. EASL clinical practice guidelines for HFE hemochromatosis.J Hepatol. 2010; 53: 3-22
- The role of iron in alcohol-mediated hepatocarcinogenesis.Adv Exp Med Biol. 2015; 815: 89-112
- Iron nutrition and tumor growth: decreased tumor growth in iron-deficient mice.Cancer Res. 1988; 48: 4168-4170
- Experimental liver cirrhosis induced by alcohol and iron.J Clin Invest. 1995; 96: 620-630
- Oxidation of tartaric acid in presence of iron.J Chem Soc Lond. 1894; 65: 899-910
- Long-term survival in patients with hereditary hemochromatosis.Gastroenterology. 1996; 110: 1107-1119
- Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies.J Hepatol. 2006; 44: 217-231
- Prevalence of hepatic iron overload and association with hepatocellular cancer in end-stage liver disease: results from the National Hemochromatosis Transplant Registry.Liver Int. 2007; 27: 1394-1401
- Synergistic interaction between excess hepatic iron and alcohol ingestion in hepatic mutagenesis.Toxicology. 2008; 254: 11-18
- Decreased cancer risk after iron reduction in patients with peripheral arterial disease: results from a randomized trial.J Natl Cancer Inst. 2008; 100: 996-1002
- Variability in hepatic iron concentration measurement from needle-biopsy specimens.J Hepatol. 1996; 25: 172-177
- Usefulness and limitations of laboratory and hepatic imaging studies in iron-storage disease.Gastroenterology. 1990; 99: 1079-1091
- Evaluation of iron stores in patients with alcoholic liver disease: role of red cell ferritin.Acta Haematol. 1988; 80: 85-88
- Screening for iron overload: lessons from the hemochromatosis and iron overload screening (HEIRS) study.Can J Gastroenterol. 2009; 23: 769-772
- Feasibility and accuracy of dual-source dual-energy CT for noninvasive determination of hepatic iron accumulation.Radiology. 2012; 262: 126-135
- Quantification of liver fat in the presence of iron and iodine: an ex-vivo dual-energy CT study.Invest Radiol. 2011; 46: 351-358
- R2∗ magnetic resonance imaging of the liver in patients with iron overload.Blood. 2009; 113: 4853-4855
- Non-invasive assessment of hepatic iron stores by MRI.Lancet. 2004; 363: 357-362
- Measurement and mapping of liver iron concentrations using magnetic resonance imaging.Ann N Y Acad Sci. 2005; 1054: 379-385
- MRI R2 and R2∗ mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients.Blood. 2005; 106: 1460-1465
- Iron-fortified MRI: effects and applications of iron-induced NMR relaxation in biological tissues.NMR Biomed. 2004; 17: 425-426
- Mechanisms of tissue-iron relaxivity: nuclear magnetic resonance studies of human liver biopsy specimens.Magn Reson Med Sci. 2005; 54: 1185-1193
- The new SQUID biosusceptometer at Oakland: first year of experience.Neurol Clin Neurophysiol. 2004; 2004: 5
- Non-invasive assessment of tissue iron overload.Hematology. 2009; : 215-221
- Non-invasive liver iron quantification by SQUID-biosusceptometry and serum ferritin iron as new diagnostic parameters in hereditary hemochromatosis.Blood Cells Mol Dis. 2002; 29: 451-458
- Total iron-overload measurement in the human liver region by the magnetic iron detector.IEEE Trans Biomed Eng. 2010; 57: 2295-2303
- Measurement of liver iron overload: noninvasive calibration of MRI-R2∗ by magnetic iron detector susceptometer.Magn Reson Med. 2012; 67: 1782-1786
- Measurement of liver iron overload by magnetic induction using a planar gradiometer: preliminary human results.Physiol Meas. 2004; 25: 315-323
- Design and validation of a histological scoring system for nonalcoholic fatty liver disease.Hepatology. 2005; 41: 1313-1321
- Inflammation-adapted liver stiffness values for improved fibrosis staging in patients with hepatitis C virus and alcoholic liver disease.Liver Int. 2015; 35: 2514-2521
- Increased liver stiffness in alcoholic liver disease: differentiating fibrosis from steatohepatitis.World J Gastroenterol. 2010; 16: 966-972
- Non-invasive diagnosis of alcoholic liver disease.World J Gastroenterol. 2014; 20: 14626-14641
- Noninvasive liver-iron measurements with a room-temperature susceptometer.Physiol Meas. 2007; 28: 349-361
- Live iron susceptometry. Magnetism in medicine.A Handbook, 1998
- Measurement of hepatic lipid: high-speed T2-corrected multiecho acquisition at 1H MR spectroscopy–a rapid and accurate technique.Radiology. 2009; 252: 568-576
- Statistical methods for assessing agreement between two methods of clinical measurement.Lancet. 1986; 1: 307-310
- Transient elastography with the XL probe rapidly identifies patients with non-hepatic ascites.Hepat Med. 2012; 4: 11-18
- Low-frequency low-field magnetic susceptibility of ferritin and hemosiderin.Biochim Biophys Acta. 2000; 1500: 186-196
- The relationship between ferritin and hemosiderin in rabbits and man.J Biol Chem. 1953; 204: 823-830
- The magnetic susceptibilities of iron deposits in thalassaemic spleen tissue.Biochim Biophys Acta. 2007; 1772: 330-337
- Cooperation of liver cells in health and disease.Adv Anat Embryol Cell Biol. 2001; 161 (1–151): Iii-xiii
Published online: May 05, 2017
Accepted: April 26, 2017
Received in revised form: April 11, 2017
Received: December 14, 2016
© 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.