Room-temperature susceptometry detects mostly hepatocyte iron in iron overload patients

Objectives: Hepatic iron overload is an important independent prognostic and cancerogenic factor in patients with chronic liver diseases such as ALD and HCV. Hepatocyte iron overload is considered to be detrimental while inflammatory cells are mandatory iron stores e.g. during inflammation. No noninvasive and cell-type specific detection of hepatic iron exists so far.

Methods: We performed room-temperature susceptometry (RTS, Insight magnetics, San Diego) to measure liver iron concentration (LIC) in 32 patients with various liver diseases. All patients underwent liver biopsy to assess cell-type specific iron scores (0 – 4) using Prussian Blue staining. In addition, fibrosis, steatosis and inflammation were assessed using the Kleiner scoring system stage. In 30 patients, LIC was also physically determined by Atomic Absorption Spectroscopy (AAS). Routine laboratory and clinical parameters were also obtained.

Results: RTS-measured LIC correlated highly significantly with LIC as determined by AAS with Pearson correlation coefficient of 0.77 (p < 0.01). To our surprise, there was a difference between AAS- and RTS-measured LIC. AAS-measured LIC correlated highly with both macrophage and hepatocyte iron. In contrast, RTS-assessed iron was only correlated significantly with the iron of hepatocytes (r = 0.47, p < 0.01). We then performed the same analysis by excluding patients with hemochromatosis since HFE-mediated iron overload is known to deplete macrophages of iron ultimately causing singular hepatocyte iron overload. In confirmation, RTS-measured LIC was only correlated with hepatocyte iron (r = 0.35, p = 0.05) in the hemochromatosis-free cohort. The areas under the receiver operating characteristic (AUROC) curve of RTS were excellent with 0.722 and 1.00, respectively, for mild and severe iron overload. The corresponding cut-off values for mild and severe hepatocellular iron overload were 1.78 and 6.85 mg/g dry weight.

Conclusion: In contrast to conventional AAS, RTS allows to detect mainly hepatocyte iron but iron in inflammatory cells. Future studies should address the question whether this is due to the abundance of hepatocyte iron or specific magnetic susceptibility of hemosiderin iron.