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使用新型室温磁化率仪对肝细胞铁进行敏感和非侵入性评估。

Sensitive and non-invasive assessment of hepatocellular iron using a novel room-temperature susceptometer.

机构信息

Dept. of Medicine, Salem Medical Center and Center for Alcohol Research and Liver Disease, University of Heidelberg, Germany.

Dept. of Radiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.

出版信息

J Hepatol. 2017 Sep;67(3):535-542. doi: 10.1016/j.jhep.2017.04.019. Epub 2017 May 5.

DOI:10.1016/j.jhep.2017.04.019
PMID:28483679
Abstract

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).

METHODS

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).

RESULTS

In vitro studies demonstrated a highly linear (r=0.998) association between RTS-signal and iron concentration, with a detection limit of 0.3mM. 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 1.4mg/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 5.0mg/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.

CONCLUSIONS

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.

摘要

背景与目的

肝脏中的铁蓄积存在于各种慢性肝病中,是影响患者生存和致癌的独立因素。我们检测了一种新型室温磁化率仪(RTS),以无创方式评估肝脏铁浓度(LIC)。

方法

前瞻性纳入 264 例有或无铁过载或肝脏疾病迹象的患者。35 例患者行肝活检并进行半定量铁检测(普鲁士蓝染色)、原子吸收光谱法(AAS,n=33)或磁共振成像(MRI,n=15)。

结果

体外研究显示,RTS 信号与铁浓度之间存在高度线性关系(r=0.998),检测下限为 0.3mM。采用优化算法,考虑到皮肤-肝包膜的距离,84%的病例可获得有效测量值。LIC-RTS 与 LIC-AAS(r=0.74,p<0.001)、LIC-MRI(r=0.64,p<0.001)和肝细胞铁(r=0.58,p<0.01)显著相关,但与巨噬细胞铁(r=0.32,p=0.30)不相关。正常 LIC-RTS 为 1.4mg/g 干重。除遗传性和输血性铁过载外,酒精性肝病患者的 LIC-RTS 也显著升高。肝细胞铁过载 1、2 和 3 级的受试者工作特征曲线(ROC)下面积(AUROC)分别为 0.72、0.89 和 0.97,其临界值分别为 2.0、4.0 和 5.0mg/g 干重。值得注意的是,严重肝铁过载(HIO)(≥2 级)检测的阳性和阴性预测值、敏感性、特异性和准确性与 AAS 相当,优于所有血清铁标志物。放血治疗后可有效监测肝脏铁耗竭情况。

结论

RTS 可快速、敏感、无创地测量 LIC。与 MRI 相比,它可能是一种经济有效的床边 LIC 筛查方法。

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