Degree Of Hepatic Iron Overload Research Articles

Technical Success and Reliability of Magnetic Resonance Elastography in Patients with Hepatic Iron Overload

This study aimed to evaluate the technical success rate and stiffness measurement reliability of two specific hepatic magnetic resonance elastography (MRE) sequences dedicated to solving susceptibility artifacts in patients with various degrees of hepatic iron overload. Thirty-seven patients with iron-overloaded liver confirmed by R2* value measurement who underwent two-dimensional (2D) spin-echo (SE) MRE and 2D SE-echo-planar-imaging (EPI) MRE were reviewed retrospectively. According to four categories based on R2* value (mild, moderate, severe elevation, and extremely severe iron overload), we compared the success rate, quality score, and liver stiffness of the two sequences. In addition, Spearman's correlation was performed to evaluate the relationship between the R2* value and liver stiffness. The overall success rates of SE MRE and SE-EPI MRE in patients with hepatic iron overload were 91.89% and 78.38%, respectively, and 100% and 78.57%, respectively, for severe elevation iron overload. In all patients, the MRE quality scores were 54 and 48 for SE MRE and SE-EPI MRE, respectively (P=0.107). There were no significant differences in liver stiffness measurements between the two MRE methods in patients with mild, moderate, and severe elevation iron-overloaded livers (P>0.6 for all), respectively. For both MRE methods, R2* value had no significant effect on the liver stiffness measurements (correlation coefficient <0.1, P >0.6 for both). In the mild and moderate elevation iron-overloaded liver, both SE MRE and fast SE-EPI MRE can provide successful and reliable liver stiffness measurement. In severe elevation iron-overloaded livers, SE MRE may be a better choice than SE-EPI MRE.

T2* map at cardiac MRI reveals incidental hepatic and cardiac iron overload

PurposeThe purpose of this study was to assess the diagnostic capabilities of cardiac magnetic resonance (CMR) T2* mapping in detecting incidental hepatic and cardiac iron overload. Materials and methodsPatients with various clinical indications for CMR examination were consecutively included at a single center from January 2019 to April 2023. All patients underwent T2* mapping at 1.5 T in a single mid-ventricular short-axis as part of a comprehensive routine CMR protocol. T2* measurements were performed of the heart (using a region-of-interest in the interventricular septum) and the liver, categorized according to the severity of iron overload. The degree of cardiac iron overload was categorized as mild (15 ms < T2* < 20 ms), moderate (10 ms < T2* < 15 ms) and severe (T2* < 10 ms). The degree of hepatic iron overload was categorized as mild (4 ms < T2* < 8 ms), moderate (2 ms < T2* < 4 ms), severe (T2* < 2 ms). Image quality and inter-reader agreement were assessed using intraclass correlation coefficient (ICC). ResultsCMR examinations from 614 patients (374 men, 240 women) with a mean age of 50 ± 18 (standard deviation) years were fully evaluable. A total of 24/614 patients (3.9%) demonstrated incidental hepatic iron overload; of these, 22/614 patients (3.6%) had mild hepatic iron overload, and 2/614 patients (0.3%) had moderate hepatic iron overload. Seven out of 614 patients (1.1%) had incidental cardiac iron overload; of these, 5/614 patients (0.8%) had mild iron overload, 1/614 patients (0.2%) had moderate iron overload, and 1/614 patients (0.2%) had severe iron overload. Good to excellent inter-reader agreement was observed for the assessment of T2* values (ICC, 0.90 for heart [95% confidence interval: 0.88–0.91]; ICC, 0.91 for liver [95% confidence interval: 0.89–0.92]). ConclusionAnalysis of standard CMR T2* maps detects incidental cardiac and hepatic iron overload in 1.1% and 3.9% of patients, respectively, which may have implications for further patient management. Therefore, despite an overall low number of incidental abnormal findings, T2* imaging may be included in a standardized comprehensive CMR protocol.

The application value of ultra-short echo time MRI in the quantification of liver iron overload in a rat model

The quantitative evaluation of liver iron concentration (LIC) is important in guiding the treatment of blood transfusion-dependent patients. Conventionally, LIC is assessed through R2*or R2 values using magnetic resonance imaging (MRI). However, most of the studies using MRI to determine iron overload were restricted by the minimum echo time, so that severe iron overload could hardly be quantified. In our study, we demonstrate a new approach to overcome the limitation of the shortest echo time using ultra-short echo time (UTE) MRI to quantify liver iron overload of varying degrees in a rat model. Sixty female Sprague-Dawley rats were included and randomly assigned into 10 equal groups. Group 1 was not injected with iron dextran. Groups 2 to 10 were intraperitoneally injected with iron dextran at a dose of 15 mg/kg every 3 days. On every 6th day, one group was randomly selected from groups 2 to 10 for MRI scanning and liver iron concentration (LIC) detection. For groups 1 to 10, images were acquired by UTE sequence using a 3.0T MR scanner, and the T2* value and R2* value were obtained (R2* =1/T2*). In addition, LIC was measured using an atomic absorption photometer. The correlation analysis between R2* value and LIC was performed and the regression equation of R2* and LIC was established and its reliability verified. For groups 1 to 10, R2* values and LIC ranged from 60.16±4.76 to 1,306.90±42.26 Hz and from 0.84±0.11 to 5.89±2.64 mg/g dry, respectively. The R2* value was linearly correlated to the LIC (r=0.897, P<0.001), and the linear regression equation was LIC = 0.005 × R2* + 1.783. The validation analysis results showed that the intragroup correlation coefficient (ICC) between the predicted and measured LIC was 89.5%. The UTE sequence could be used for quantification of varying degrees of hepatic iron overload in the rat model, and the LIC could be predicted by using the R2* value on an MR 3.0T scanner.

PWE-124 Role of acoustic radiation force impulse (arfi) elastography in non-invasive assessment of liver fibrosis in iron overload: a single centre experience

Introduction The predictive accuracy of ARFI elastography (virtual touch quantification, VTq ™) for the non-invasive assessment of liver fibrosis is increasingly recognised, particularly in viral hepatitis. There is less information on its role in other aetiologies of chronic liver disease. We report the results of a preliminary study examining liver stiffness (LS) measurements by ARFI in patients with iron overload. Method Forty-nine measurements of LS in 43 patients were performed to investigate possible iron overload. LS estimation by ARFI was performed using a standard validated protocol with a Siemens Acuson S2000 + 4C1 probe. Biopsies were performed in 19 (39%) from the same region of liver, immediately after LS measurement. Clinical, biochemical, ultrasonic and histopathological data were collated retrospectively. Predictive accuracy variables were determined for fibrosis stage, using both standard published and local 1 calibrations. Results Aetiologies of iron overload in the biopsy cohort were: genetic haemochromatosis (n = 4); hyperferritinaemia with NAFLD or alcohol excess (8); hyperferritinaemia of unknown cause (3); transfusion-dependent thalassaemia (2); C282Y/H63D compound heterozygote (1); and high ferritin from renal cell carcinoma (1). Validation criteria for ARFI technical quality (SD/mean 1 ; b) the exclusion of ≥F2 fibrosis were 0.80, 0.78, 0.80 and 0.78, respectively, with both calibrations. No correlation was seen between LS and either a) necro-inflammation, histological grade of siderosis or scan technical quality; or b) serum ferritin levels. Conclusion ARFI elastography may prove a useful non-invasive technique for excluding F2 fibrosis and identifying F4 cirrhosis secondary to iron overload. The high incidence of dual pathology, particularly NAFLD and alcohol-related, may have influenced predictive accuracy in this small “real world” cohort. The degree of hepatic iron overload did not correlate with LS. Further biopsy-controlled studies are needed to validate the role of ARFI in this patient group. Disclosure of interest None Declared. Reference Sherman D, et al . J Hepatol. 2014;60(1):S413

Evaluation of Hepatic Iron Overload in Chinese Children With β-Thalassemia Major

Patients with β-thalassemia major require long-term blood transfusions, resulting in hepatic iron overload. Thirty-five Chinese children with β-thalassemia major were recruited in the present studies. Hepatic iron overload was evaluated by histological grading. The relationships between hepatic iron overload and both serum biochemical markers and magnetic resonance imaging (MRI) examination were studied. The majority of the patients showed high degrees of hepatic iron overload by histological study. The degree of hepatic iron overload was correlated with serum ferritin (r = .70, P < .01), hyaluronic acid (r = .58, P = .011), and type III precollagen (r = .55, P = .035). Moreover, hepatic iron overload showed a negative correlation with liver to muscle signal intensity ratio (r = −.44, P = .012), and a positive correlation with red marrow area percentage (r = .52, P < .01). These results indicated that hepatic iron overload might be assessed by serum biochemical markers and MRI examination.

Noninvasive measurement of liver iron concentration at MRI in children with acute leukemia: initial results

Routine assessment of body iron load in patients with acute leukemia is usually done by serum ferritin (SF) assay; however, its sensitivity is impaired by different conditions including inflammation and malignancy. To estimate, using MRI, the extent of liver iron overload in children with acute leukemia and receiving blood transfusions, and to examine the association between the degree of hepatic iron overload and clinical parameters including SF and the transfusion iron load (TIL). A total of 25 MRI measurements of the liver were performed in 15 children with acute leukemia (mean age 9.75 years) using gradient-echo sequences. Signal intensity ratios between the liver and the vertebral muscle (L/M ratio) were calculated and compared with SF-levels. TIL was estimated from the cumulative blood volume received, assuming an amount of 200 mg iron per transfused red blood cell unit. Statistical analysis revealed good correlation between the L/M SI ratio and TIL (r = -0.67, P = 0.002, 95% confidence interval CI = -0.83 to -0.34) in patients with acute leukemia as well as between L/M SI ratio and SF (r = -0.76, P = 0.0003, 95% CI = -0.89 to -0.52). SF may reliably reflect liver iron stores as a routine marker in patients suffering from acute leukemia.

The role of MR imaging in detection of hepatic iron overload in patients with cirrhosis of different origins

BackgroundThere are many pathological conditions with hepatic iron overload. Classical definite diagnostic methods of these disorders are invasive and based on a direct tissue biopsy material. For the last years the role of MR imaging in liver diagnostics has been increasing. MRI shows changes of liver intensity in patients with hepatic iron overload. Changes in MR signal are an indirect consequence of change of relaxation times T2 and T2*, that can be directly measured.The purpose of the study was to evaluate usefulness of MR imaging in the detection of hepatic iron overload in patients with cirrhosis of different origins.MethodsMR imaging at 1.5T was prospectively performed in 44 patients with liver cirrhosis who had undergone liver biopsy with histopathological assessment of hepatic iron deposits. In all patients the following sequences were used: SE, Express, GRE in T2 and T1-weighted images. Signal intensity (SI) was measured on images obtained with each T2 weighted sequence by means of regions of interest, placed in the liver and paraspinal muscles. The correlation between iron overload, histopathological score, serum ferritin and SI ratio was analyzed.ResultsIn 20 patients with iron overload confirmed by the biopsy, the liver parenchyma demonstrated lower signal intensity than that of paraspinal muscles. This effect was visible only in 8 patients with hepatic iron overload in Express T2-weighted images. Higher signal intensity of liver than that of skeletal muscles on GRE - T2 weighted images was noted in 24 patients with cirrhosis and without elevated hepatic iron concentration. We observed a correlation between low and high iron concentration and liver to muscle SI ratio.ConclusionMR imaging is a useful and fast noninvasive diagnostic tool for the detection of liver iron overload in patients with cirrhosis of different origins.Liver to muscle SI ratio in GRE-T2-weighted sequence facilitates to differentiate patients with low and high degree of hepatic iron overload, which correlates with the origin of liver cirrhosis.

Hepatocellular carcinoma caused by iron overload: A possible mechanism of direct hepatocarcinogenicity

Background/aims Excess hepatic iron may be both directly and indirectly carcinogenic. The aim of this study was to determine if generation of reactive oxygen species and the resulting oxidative damage induced by free hepatic iron is directly hepatocarcinogenic. Methods Sixty male Wistar albino rats were iron-loaded by ferrocene supplementation of their diet. Biochemical parameters of oxidative damage and lipid peroxidation, DNA unwinding and strand breaks, and the Ames Mutagenesis Test were measured at 4 monthly intervals and correlated with the degree of hepatic iron overload, the presence of iron-free preneoplastic foci in the liver, and the development of hepatocellular carcinoma in comparison with 60 control rats. Results Levels of lipid hydroperoxides, malonaldehyde, 8-isoprostane and 8-hydroxy-2′-deoxyguanosine increased, reaching peak concentrations at 20–24 months, and correlating with an increase in the rate of DNA unwinding, strand breaks, and positive Ames Tests. Iron-free neoplastic foci became evident at 16 months and thereafter increased in number. Preneoplastic foci were present in five of eight rats remaining at 32 months and HCC had developed in one of the five. Conclusions Our findings are compatible with the hypothesis that the direct hepatocarcinogenic effect of free iron is mediated by the generation of oxygen reactive species and oxidative damage that are mutagenic and carcinogenic.

Increased hepatic iron and cirrhosis: No evidence for an adverse effect on patient outcome following liver transplantation

It has been suggested that preexisting severe hepatic iron overload may adversely affect outcome after liver transplantation. The pathogenesis of iron overload in cirrhosis in the absence of hemochromatosis gene ( HFE) mutations is poorly understood. The relationships between liver disease severity and etiology, degree of hepatic iron overload, and post-liver transplantation outcome were studied in 282 consecutive adult patients with cirrhosis. Thirty-seven percent of patients had stainable hepatic iron. Increased hepatic iron concentration was significantly associated with more severe liver disease ( P < .001), male sex ( P = .05), the presence of spur cell anemia ( P < .0001), and hepatocellular liver disease ( P < .0001). The HFE mutations were uncommon in patients with increased hepatic iron stores. Increased hepatic iron concentration was not associated with greater utilization of resources or a lower survival after liver transplantation. Child-Pugh score at the time of liver transplantation was the only independent variable affecting patient survival ( P = .0008). In summary, our data suggest that the severity of the liver disease rather than hepatic iron concentration is the most important determinant of outcome after liver transplantation and that, in general, increasing hepatic iron concentration in cirrhosis is a surrogate marker of the severity of the underlying liver disease. (Hepatology2000;32:1200-1207.)

Iron overload in bone marrow transplant recipients.

We examined the degree of hepatic iron overload in patients receiving marrow transplant for hematologic malignancy and evaluated a new method of morphometric analysis of marrow iron content as a means of estimating hepatic iron stores in these patients. The iron content of marrow and liver specimens from 10 consecutive patients who died between 50 and 100 days after transplant was determined by spectrophotometry. Their mean age was 34.9 years (range 10-59). The mean time to death from disease onset was 2.2 years (0.5-8.7). Patients had received 30.2 +/- 17.4 units of red cells during the transplant period and 47.6 +/- 25.9 red cell units from diagnosis to death. The median hepatic iron concentration (HIC) was 4307 microg/g dry weight (range 1832-13120; normal 530-900) and the median hepatic iron index (HIC (micromol/g dry weight/age (years)) was 3.85 (0.76-8.14). The median biochemical marrow iron content was 1999 microg/g dry weight (range 932-3942). Morphometric analysis of the marrow iron content was performed on digital photomicrographs of a single Prussian blue-stained section of marrow. Strong correlations were demonstrated between morphometric marrow iron content and (1) biochemical marrow iron content (r = 0.8, P= 0.006) and (2) biochemical hepatic iron index (r = 0.82, P = 0.004). We conclude that marrow transplant recipients have a high liver iron content at 50-100 days post transplant with the hepatic iron index in the hereditary hemochromatosis range. Computerized morphometric marrow iron determination is a readily available means of estimating hepatic iron stores in these patients.

Iron overload following bone marrow transplantation in children: MR findings.

The purpose of this study was to determine the incidence of post-transfusional iron overload in children after bone marrow transplantation by reviewing their magnetic resonance imaging (MR) findings. We reviewed the abdominal MR studies of 13 children after autologous bone marrow transplantation. Nine of the children had also undergone MR prior to transplantation. Iron deposition in the liver, spleen and bone marrow was graded semi-quantitatively on both T1- and T2-weighted images. Serum ferritin levels and number of blood units given after bone marrow transplantation were recorded. None of the pre-transplantation MR studies revealed iron overload. After bone marrow transplantation, three children showed normal liver and spleen. Iron overload in the liver was noted in ten patients (77 %), six of whom also showed iron overload in the spleen (46 %) and five in the bone marrow (38.5 %). The degree of hepatic iron overload was correlated significantly and splenic iron overload was correlated weakly with the number of blood transfusions (P = 0.01 and P > 0.01, respectively), but neither was correlated with the serum ferritin level. Iron overload commonly accompanies bone marrow transplantation. The observed pattern of iron deposition, in which the spleen was uninvolved in 40 % of patients demonstrating iron overload, is not typical of post-transfusional hemochromatosis.

Hepatic iron overload: diagnosis and quantification with MR imaging.

The aim of this study was to assess the sensitivity of MR imaging in the diagnosis of liver hemochromatosis and its ability to quantify hepatic iron concentration (HIC). MR images were prospectively obtained in 58 patients suspected to have hemochromatosis. We used a scanner with a 0.5-T magnet and two sequences: gradient-echo T1-weighted (400/12 [TR/TE], 90 degrees flip angle) and gradient-echo T2*-weighted (700/30, 30 degrees flip angle) sequences. Measurement of the liver-to-muscle signal-intensity ratio was compared with the HIC value measured at biopsy for each patient. Both MR sequences showed significant correlation between decreased signal-intensity ratios and increased HIC (r = -.87 for T1-weighted sequences and r = -.74 for T2*-weighted sequences). The sensitivity and specificity of the T2*-weighted sequence (signal-intensity ratio < 0.8) to detect iron overload (HIC > 36 mumol/g) were 91% and 88%, respectively. The best correlation was obtained with T2*-weighted sequences, when patients had an HIC less than 100 mumol/g (r = -.71); with T1-weighted sequences, the best correlation was obtained when patients had an HIC of 100-324 mumol/g (r = -.67). We found a significant correlation between the HIC revealed on MR images, calculated from both sequences, and that measured at biopsy when patients had an HIC of less than 300 mumol/g (r = -.93, p < .01). MR imaging shows promise in differentiating normal from abnormal hepatic iron concentration and in grossly quantifying moderate degrees of hepatic iron overload.

Hepatic iron overload: Diagnosis and quantification by noninvasive imaging

The diagnostic efficacy of magnetic resonance (MR) and computed tomography (CT) for detection and quantification of hepatic iron was assessed in a series of patients under investigation for clinical or biochemical evidence of hepatic iron overload. Thirty patients underwent MR imaging (SE 30,60/1000 or SE 30,60/2000) at 0.5 Tesla with calculation of hepatic T2 and liver to paraspinous muscle signal intensity ratios. Twenty-nine patients also had measurement of hepatic attenuation on noncontrast CT images. Results of these imaging studies were correlated in all patients with quantitative iron determination from liver biopsy specimens. The best predictor of liver iron among parameters studied was the ratio of the signal intensities of liver and paraspinous muscle (L/M) on a SE 60/1000 sequence. Both MR using L/M ratios and CT were sensitive methods for detection of severe degrees of hepatic iron overload with 100% of patients with hepatic iron on biopsy greater than 600 micrograms/100 mg liver dry weight detected on the basis of L/M less than 0.6 or CT attenuation greater than 70 Hounsfield units (HU). The MR parameter, however, was more specific than CT (100 vs 50%) and showed a higher degree of correlation with quantitated hepatic iron from biopsy. T2 measurements showed poor correlation with hepatic iron, due to difficulty in obtaining precise T2 measurements in vivo when the signal intensity is low. None of the parameters utilized was sensitive for detecting mild or moderate degrees of hepatic iron overload. We conclude that MR and CT are sensitive techniques for noninvasive detection of severe hepatic iron overload, with MR providing greater specificity than CT.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantification of hepatic iron with CT and MRI: Practical considerations

The diagnostic efficacy of magnetic resonance (MR) and computed tomography (CT) for detection and quantification of hepatic iron was assessed in a series of patients under investigation for clinical or biochemical evidence of hepatic iron overload. Thirty patients underwent MR imaging (SE 30,60/1000 or SE 30,60/2000) at 0.5 Tesla with calculation of hepatic T2 and liver to paraspinous muscles signal intensity ratios. Twenty-nine patients also had measurement of hepatic attenuation on noncontrast CT images. Results of these imaging studies were correlated in all patients with quantitative iron determination from liver biopsy specimens. The best predictor of liver iron among parameters studied was the ratio of the signal intensities of liver and paraspinous muscle (L/M) on a SE 60/1000 sequence. Both MR using L/M ratios and CT were sensitive methods for detection of severe degrees of hepatic iron overload with 100% of patients with hepatic iron on biopsy > 600 μg/100 mg liver dry weight detected on the basis of L/M 70 Hounsfield units (HU). The MR parameter, however, was more specific than CT (100 vs 50%) and showed a higher degree of correlation with quantitated hepatic iron from biopsy. T2 measurements showed poor correlation with hepatic iron, due to difficulty in obtaining precise T2 measurements in vivo when the signal intensity is low. None of the parameters utilized was sensitive for detecting mild or moderate degrees of hepatic iron overload. We conclude that MR and CT are sensitive techniques for noninvasive detection of severe hepatic iron overload, with MR providing greater specificity than CT. Lesser degrees of iron deposition, however, may go undetected by our current imaging techniques.

Hepatic iron overload: Diagnosis and quantification by noninvasive imaging

The diagnostic efficacy of magnetic resonance (MR) and computed tomography (CT) for detection and quantification of hepatic iron was assessed in a series of patients under investigation for clinical or biochemical evidence of hepatic iron overload. Thirty patients underwent MR imaging (SE 30,60/1000 or SE 30,60/2000) at 0.5 Tesla with calculation of hepatic T2 and liver to paraspinous muscle signal intensity ratios. Twenty-nine patients also had measurement of hepatic attenuation on noncontrast CT images. Results of these imaging studies were correlated in all patients with quantitative iron determination from liver biopsy specimens. The best predictor of liver iron among parameters studied was the ratio of the signal intensities of liver and paraspinous muscle (L/M) on a SE 60/1000 sequence. Both MR using L/M ratios and CT were sensitive methods for detection of severe degrees of hepatic iron overload with 100% of patients with hepatic iron on biopsy > 600 Μg/ 100 mg liver dry weight detected on the basis of L/M 70 Hounsfield units (HU). The MR parameter, however, was more specific than CT (100 vs 50%) and showed a higher degree of correlation with quantitated hepatic iron from biopsy. T2 measurements showed poor correlation with hepatic iron, due to difficulty in obtaining precise T2 measurements in vivo when the signal intensity is low. None of the parameters utilized was sensitive for detecting mild or moderate degrees of hepatic iron overload.