scholarly journals Utility of Transient Elastography (Fibroscan) in Estimating Hepatic Iron Concentration in Comparison to MRI in Patients with Transfusion Dependent Hemoglobinopathies

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4888-4888
Author(s):  
Hatoon Ezzat
Keyword(s):  
Regression Analysis ◽  
Linear Regression ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Transient Elastography ◽  
Linear Regression Analysis ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Hepatic Iron ◽  
Hepatic Iron Concentration

Abstract Background Patients with severe hereditary anemias (e.g. β-Thalassemia Major) are transfusion-dependent for survival. Current guidelines suggest monitoring serum ferritin every three months and annual MRI to assess hepatic and cardiac iron load1. However, MRI, particularly the R2 sequence (FerriScan) which has high specificity and sensitivity in estimating the liver iron concentration, is expensive and not always readily available. Transient elastography (FibroScan) measures liver's stiffness and predicts fibrosis. Previous studies have suggested its utility in other conditions that increase liver stiffness, such as amyloidosis2and perhaps iron overload. Aim To determine if FibroScan value correlates with hepatic iron concentration estimated using R2 MRI (FerriScan), and/or serum ferritin level. Methods A prospective cross-sectional study was conducted at a university-affiliated tertiary care center (St. Paul’s Hospital, Vancouver, BC) in 2013 and 2014. Inclusion criteria: Age ≥ 19 years with transfusion-dependent hereditary anemias. Exclusion criteria: liver cirrhosis, primary liver disease (e.g. Wilson’s disease, hereditary hemochromatosis), and chronic viral hepatitis (e.g. Hepatitis B, C and HIV). In addition to having annual MRI and ferritin levels monitored every three months, subjects underwent FibroScan within six months of MRI in 2013. In 2014, participants were invited to undergo repeat FibroScan within three months of the annual MRI. Linear regression analysis was used to determine if there is any correlation/linear fit between FibroScan result, MRI result, and ferritin levels. This study was approved by the University of British Columbia Research Ethics Board. Results 20 subjects have been recruited as of August 1, 2014, with 35 and 33 complete FibroScan and MRI results, respectively. 14 (70%) were female. Mean age was 30.7±9.8 years. Most common primary diagnosis was transfusion-dependent beta-thalassemia (Major and intermedia) (n=17). Linear regression analysis showed a weakly positive correlation between hepatic iron concentrations estimated with R2 MRI (FerriScan) and ferritin levels (R2=0.29; p=0.004), when they are performed within four weeks apart. The correlation remained statistically significant when all subjects were included regardless of time lapse between the two investigations (R2=0.30; p=0.001). However, FibroScan values did not appear to correlate with MRI, regardless of whether the scans are performed within six months (R2=0.011; p=0.58) or three months apart (R2=0.035; p=0.44). Similarly, there was no correlation between FibroScan and Ferritin (R2=0.022; p=0.49) when the investigations were performed within 4 weeks part. Conclusion Interim analysis did not demonstrate any correlation between FibroScan result and MRI-estimated hepatic iron concentration. A final analysis will be performed upon complete formal evaluation of the remaining MRI and FibroScan data. References Remacha A, Sanz C, Contreras E, et al. Guidelines on haemovigilance of post-transfusional iron overload. Blood Transfus. 2013; 11(1): 128-139Loustaud-Ratti V, Cypierre A, Rousseau A, et al. Non-invasive detection of hepatic amyloidosis: Fibroscan, a new tool. Amyloid 2013; 18(1): 19-24 Disclosures No relevant conflicts of interest to declare.

Exome Sequencing Identifies Genes and Variant Alleles Associated With Severity Of Iron Overload In Hemochromatosis HFE C282Y Homozygotes

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 179-179
Author(s):  
Christine E. McLaren ◽  
Mary J. Emond ◽  
Pradyumna D. Phatak ◽  
Paul C. Adams ◽  
V. Nathan Subramaniam ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Concentration ◽  
Missense Variant ◽  
Dry Weight ◽  
P Value ◽  
Hepatic Iron ◽  
Common Variants ◽  
Iron Stores ◽  
Hepatic Iron Concentration

Abstract Variability in the severity of iron overload among homozygotes for the HFE C282Y polymorphism is one of the major problems extant in our understanding of hereditary hemochromatosis (HH). We conducted exome sequencing of DNA from C282Y homozygotes with markedly increased iron stores (cases) and C282Y homozygotes with normal or mildly increased iron stores (controls) to identify rare and common causal variants associated with variability of disease expression in HH. Criteria for cases included serum ferritin >1000 µg/L at diagnosis, and (a) mobilized body iron >10 g by quantitative phlebotomy, and/or (b) hepatic iron concentration >236 µmol/g dry weight. Criteria for controls included (a) serum ferritin <300 µg/L, or (b) age ≥50 y with ≤3.0 g iron removed by phlebotomy or age ≥40 y with ≤2.5 g iron removed by phlebotomy to achieve serum ferritin <50 µg/L. Deep sequencing of the full exome was performed in 33 cases and 14 controls. After quality control filtering, the dataset included 82,068 SNPs and 1,403 insertions/deletions (indels). Our initial analysis tested for differences in the distribution of variants between groups for each gene separately using the Sequence Kernel Association Test (SKAT) that includes rare and common variants but downweights the contribution of common variants to the test statistic. Only non-synonymous variants were included in the by-gene tests. Principal components were constructed from the exome variants to adjust for possible confounding by ancestry and to confirm no ancestral outliers. All study participants were male, and all clustered closely together within a larger group of Europeans in a principal components analysis of ancestry. Mean (SD) ages at presentation were 54 (11.0) y and 56 (9.4) y for cases and controls, respectively. Median serum ferritin was 2788 µg/L in those with increased iron stores and 309 μg/L in those with normal or mildly increased iron stores. The median transferrin saturation (94%) was greater in cases than in the comparison group (70%). In a preliminary analysis, we found 9 genes associated with case-control status. To separate effects of alcohol use and/or alcohol addiction variants, an analysis was conducted to compare the 13 controls and 22 cases who reported never using alcohol or only very light use. The two most significant genes identified in this comparison were GNPAT (p=7.4x10-6) and CDHR2 (p=2.8x10-4). A quantile-quantile (QQ) plot is shown in the Figure, comparing the observed distribution of –(log10p-values) from 10,337 genes to the expected uniform distribution if there were no variants modifying severity of expression, and gives evidence of the effect of the GNPAT gene.Figure 1Figure 1. Inspection of the two variants contributing to the GNPAT by-gene p-value revealed one missense variant (rs11558492) for which 0/13 controls had a polymorphism, while 16/22 cases had at least one missense variant, and one case was homozygous for this missense variant. The latter case presented at the early age of 26 with a serum ferritin of 1762 µg/L, 4+ hepatocellular iron and hepatic iron concentration of 284.4 µmol/g dry weight. GNPAT (aka DHAPAT) mutations/deletions have been found in peroxisomal disease, a class of diseases in which increased hepatic iron is observed (Biochim Biophys Acta 1801:272-280, 2010). GNPAT rs11558492 is common among people of European descent but might interact with aberrant HFE to increase risk of hepatic iron overload. Three rare variants in CDHR2 accounted for its low p-value, having a cumulative frequency of 4/13 among controls and 0/22 among cases: rs115050587, rs752138, rs143224505 with minor allele frequencies, MAF = 1.4%, 4.7% and 0.06%, respectively. The first two polymorphisms are predicted to be highly damaging by PolyPhen2 and the third probably damaging. Expression levels of CDHR2 recently have been associated with increased hepatocyte iron and elevated serum ferritin in liver allograft patients (J Clin Invest 122:368-382, 2012). These data indicate associations between iron status in HFE C282Y homozygotes and genes with previous links to iron overload that may modify severity of disease expression. Of note, the data suggest that more than one modifier gene may be involved in determining severity of disease in HFE C282Y homozygotes. Our results identify candidate genes for expanded studies that would examine their functional significance for iron absorption and metabolism. Disclosures: No relevant conflicts of interest to declare.

Sa1606 – Is Serum Ferritin a Reliable Measure of Iron Overload When Compared to Hepatic Iron Concentration?

2019 ◽  
Vol 156 (6) ◽  
pp. S-1251
Author(s):  
Barra P. Neary ◽  
Mohammad Tayyub ◽  
Asya Tacheva ◽  
Aidan Quinn ◽  
Greg Martin ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Concentration ◽  
Hepatic Iron ◽  
Reliable Measure ◽  
Hepatic Iron Concentration

scholarly journals Excessive adiposity is associated with an inflammation induced elevation in serum hepcidin, serum ferritin and increased risk of iron overload

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Aoibhín Moore Heslin ◽  
Aisling O' Donnell ◽  
Maria Buffini ◽  
Anne Nugent ◽  
Janette Walton ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Linear Regression ◽  
Iron Overload ◽  
Body Fat ◽  
Serum Ferritin ◽  
Linear Regression Analysis ◽  
Elevated Serum ◽  
Metabolic Effects ◽  
Serum Hepcidin ◽  
Excessive Adiposity

AbstractExcess body fat is associated with the production of pro-inflammatory molecules from dysfunctional adipose tissue resulting in systemic inflammation. Inflammation stimulates expression of the iron regulatory hormone hepcidin, resulting in elevated serum ferritin and iron overload in metabolic tissues. Hepcidin driven iron maldistribution may be implicated in the development of metabolic diseases such as Type 2 diabetes and CVD. The aim of this study was to investigate the effect of body fat and the associated inflammation on markers of iron homeostasis.Analyses were based on data from the cross-sectional National Adult Nutrition Survey (2008–2010) (www.iuna.net). Percentage body fat (BF%) of participants (n = 1211) was measured by a Tanita BC420MA device. Participants were classified as healthy, overweight or obese based on age and gender-specific BF% ranges. Serum ferritin and serum hepcidin were measured using immunoturbidimetric immunoassays. ANCOVA with Bonferroni post hoc (p < 0.05) was used to compare anthropometric parameters, biochemical markers of iron status and inflammation and nutrient intakes between BF% groups. Predictors of serum hepcidin and serum ferritin were determined using linear regression analysis.In the population 42% were classified as healthy, 33% as overfat and 25% as obese. Serum hepcidin was significantly elevated in obese participants (8.42ng/ml ± 4.2) compared to their healthy counterparts (6.49ng/ml ± 3.9)(p < 0.001). Significantly higher serum ferritin was observed in obese (223ng/ml ± 170) and overfat males (166ng/ml ± 120) compared to healthy males (135ng/ml ± 91)(p < 0.001). A significant percentage of overweight (20%) and obese (32%) participants were at severe risk of iron overload compared to healthy participants (8%)(p < 0.001). No significant differences in dietary iron intakes were observed between BF% groups. Linear regression analysis indicated that BF% was a significant (p < 0.001) predictor of hepcidin in males (β = 0.327) and females (β = 0.226). IL-6 (β = 0.317,p < 0.001) and TNFα (β = 0.229,p < 0.001) were the strongest inflammatory predictors of hepcidin in females only. In males, leptin was a positive predictor (β = 0.159,p = 0.003) of hepcidin, while adiponectin displayed a negative predictive relationship (β = -0.145,p = 0.001)Our results indicate that excessive adiposity is associated with elevated serum ferritin and hepcidin independent of dietary intake. Cytokines are a potential driver of hepcidin in females, with adipose-derived hormones seeming to have the greater effect in males. These results may help to elucidate the relationship between obesity and dysregulated iron metabolism. Further research is required to investigate the metabolic effects of hepcidin-induced iron overload in those with excess body fat.

Safety of Deferasirox (Exjade®) in Patients with Transfusion-Dependent Anemias and Iron Overload Who Achieve Serum Ferritin Levels <1000 Ng/Ml during Long-Term Treatment

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5423-5423 ◽  
Author(s):  
John B Porter ◽  
Antonio Piga ◽  
Alan Cohen ◽  
John M Ford ◽  
Janet Bodner ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Abdominal Pain ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Safety Profile ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Liver Iron ◽  
Long Term Treatment ◽  
Baseline Characteristics

Abstract Background: Maintaining serum ferritin (SF) levels below 1000 ng/mL has been reported to predict longer survival and a reduced risk of complications (eg heart failure) in patients with thalassemia major. Experience with deferoxamine (Desferal®, DFO) has indicated that the toxicity of DFO may increase as SF levels decrease. A target SF value in the deferasirox clinical trials was not specified per protocol, but was determined by the individual investigators. This analysis evaluates the safety of deferasirox (Exjade®) in a cohort of adult and pediatric patients with transfusion-dependent anemias and iron overload from two large clinical trials (107 and 108) who were chelated to SF levels &lt;1000 ng/mL. Methods: In core studies 107 and 108, frequently-transfused patients with chronic anemias ≥2 years old received deferasirox 5–30 mg/kg/day for 1 year. Eligible patients were then enrolled in 4-year extension trials, where initial dosing was based on the end of core study liver iron concentration; dose adjustments were based on SF levels. Patients eligible for this analysis had an initial SF ≥1000 ng/mL. Patients who achieved a SF level &lt;1000 ng/mL on ≥2 consecutive visits, any time after starting deferasirox, were identified. The number of days when SF was &lt;1000 ng/mL was calculated for each patient. AEs in these patients were calculated for the entire period on deferasirox, and for the period following the first SF measurement of &lt;1000 ng/mL, irrespective of future SF levels. Results: 474 patients were included in this analysis: underlying anemias were β-thalassemia (n=379), myelodysplastic syndromes (n=43), Diamond-Blackfan anemia (n=30) and other anemias (n=22). Overall, 13.5% patients achieved SF&lt;1000 ng/mL in year 1, 18.6% in year 2, 25.7% in year 3, 32.5% in year 4 and 36.7% by the time of this analysis. Therefore, overall 174 patients (36.7%) reached a SF level &lt;1000 ng/mL on ≥2 consecutive visits, while in 300 patients SF levels remained ≥1000 ng/mL. The median period for a SF value &lt;1000 ng/mL was 149 days [range 18–1726]. Patient demographics, baseline characteristics and safety profiles of the two groups throughout deferasirox treatment are shown in Table 1. At month 54, median SF levels in the &lt;1000 and &gt;1000 ng/mL groups were 872 and 2118 ng/mL, respectively. The incidence of drug-related AEs (gastrointestinal, renal and liver) did not appear to increase during the periods after SF levels first decreased below 1000 ng/mL (data not shown). Table 1. Demographics, baseline characteristics and safety profile of patients who achieved SF levels &lt;1000 ng/mL and patients who did not Patients who achieved SF &lt;1000 ng/mL Patients who did not achieve SF &lt;1000 ng/mL *Investigator-assessed; SCr, serum creatinine; ULN, upper limit of normal; ALT, alanine aminotransferase n 174 300 Male:female 85:89 145:155 Mean age ± SD, years 23.8 ± 16.7 23.5 ± 18.2 &lt;16, n (%) 65 (37.4) 123 (41.0) ≥16, n (%) 109 (62.6) 177 (59.0) Enrolled from study 107:108 120:54 175:125 Median exposure to deferasirox, months 56.3 45.2 Mean actual deferasirox dose, mg/kg/day 20.3 22.9 Median baseline SF, ng/mL 1791 2883 Drug-related AEs* (≥5% in either group), n (%) Nausea 26 (14.9) 38 (12.7) Diarrhea 17 (9.8) 42 (14.0) Vomiting 14 (8.0) 25 (8.3) Abdominal pain 12 (6.9) 32 (10.7) Upper abdominal pain 6 (3.4) 20 (6.7) Rash 9 (5.2) 16 (5.3) Audiological abnormalities 7 (4.0) 4 (1.3) Ophthalmological abnormalities 4 (2.3) 5 (1.7) Two consecutive SCr increases &gt;33% above baseline and above ULN 26 (14.9) 36 (12.0) Increase in ALT &gt;10×ULN on at least 1 visit 12 (6.9) 20 (6.7) Baseline levels elevated 6 (3.4) 16 (5.3) Conclusions: Over the core and extension phases of these clinical studies, the safety profile of patients achieving SF levels &lt;1000 ng/mL was similar to that observed in patients who did not achieve SF levels &lt;1000 ng/mL. There was also no apparent increase in AEs associated with a decrease in SF levels &lt;1000 ng/mL. In particular, no increase in the proportion of patients with creatinine increases &gt;33% above baseline and ULN or with ALTs &gt;10×ULN were observed in these patients. These findings suggest that ironoverloaded patients can be safely chelated with deferasirox to low SF levels.

Liver Transient Elastography (FibroScan) Correlates with Liver Iron Concentration and Reflects Liver Fibrosis In Patients with Sickle Cell Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1646-1646 ◽  
Author(s):  
Ersi Voskaridou ◽  
Maria Schina ◽  
Eleni Plata ◽  
Dimitrios Christoulas ◽  
Maria Tsalkani ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Iron Overload ◽  
Hepatic Fibrosis ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Transient Elastography ◽  
Iron Concentration ◽  
Liver Stiffness ◽  
Cell Disease ◽  
Liver Iron

Abstract Abstract 1646 Liver transient elastography (FibroScan) is an interesting new technology that allows estimation of hepatic fibrosis through measurement of liver stiffness. The technique is based on changes in tissue elasticity induced by hepatic fibrosis and is considered as a noninvasive, reproducible and reliable method to assess hepatic fibrosis as well as to diagnose liver cirrhosis. Hepatic iron overload is a severe complication of chronic transfusion therapy in patients with hemoglobinopathies and plays an important role in the development of hepatic fibrosis and cirrhosis. Iron overload is present in several cases of sickle cell disease (SCD) including sickle cell anemia (HbS/HbS) and double heterozygous sickle-cell/beta-thalassemia (HbS/beta-thal). The aim of the study was to evaluate liver fibrosis by measuring the liver rigidity (Liver Stiffness Measurement, LSM, kPascals) using transient elastography (FibroScan, Echosens, Paris, France) in patients with SCD and explore possible correlations with clinical and laboratory characteristics of the patients, including iron overload. We studied 110 consecutive patients with SCD who are followed-up in the Thalassemia Center of Laikon General Hospital in Athens, Greece. Forty-four patients were males and 66 females; their median age was 44 years (range: 21–73 years). Twenty-two patients had HbS/HbS and 88 patients had HbS/beta-thal. On the day of Fibroscan, all patients had a thorough hematology and biochemical evaluation, including hemoglobin, reticulocyte counts, serum ferritin, liver biochemistry, bilirubin, lactate dehydrogenase (LDH) and serology for viral hepatitis. Liver iron concentration was evaluated by magnetic resonance imaging (MRI) T2* in all patients. The median LSM of all patients was 6.1 kPascals (range: 3.4–48.8 kPascals) with no differences between HbS/HbS (6.1 kPascals, 3.5–17.3 kPascals) and HbS/beta-thal (6.1 kPascals, 3.4–48.8 kPascals) patients (p=0.835). LSM values strongly correlated with liver MRI T2* values (r=0.337, p<0.001), serum ferritin (r=0.328, p=0.001), number of transfusions (r=0.332, p=0.001), bilirubin (r=0.299, p=0.003), LDH (r=0.287, p=0.004), Hb (r=-0.275, p=0.006) and reticulocyte counts (r=0.244, p=0.015). LSM values showed also strong positive correlations with biochemical indicators of liver function: gamma-glutamyl transpeptidase (r=0.522, p<0.0001), glutamic oxaloacetic transaminase (r=0.484, p<0.0001), glutamic pyruvic transaminase (r=0.422, p<0.0001), alkaline phosphatase (r=0.334, p=0.001), gamma-globulin (r=0.296, p=0.005) and weak correlation with PT-International Normalized Ratio (r=0.184, p=0.094). The above correlations were similar in patients with HbS/HbS and in patients with HbS/beta-thal. However, in HbS/HbS patients the correlation between LSM and liver T2* values was very strong (r=0.770, p=0.001). Patients who were regularly transfused had higher values of LSM (median: 6.7 kPascals, range: 2.3–48.8 kPascals) compared with patients who were sporadically transfused or were not transfused (4.4 kPascals, 3.6–17.5 kPascals, p=0.003). Patients who were under iron chelation therapy had lower values of LSM (6.3 kPascals, 3.4–15 kPascals) compared with those who did not receive iron chelators (13.9 kPascals, 8.5–17.3 kPascals, p=0.013). We found no correlations between the presence of HBV or HCV positivity and the levels of LSM. In conclusion, FibroScan may constitute a reliable and easy to apply noninvasive method to assess liver fibrosis in patients with SCD; the strong correlations between LSM values with MRI T2* values and serum ferritin supports this observation. Furthermore, FibroScan seems also to reflect the presence of chronic hepatic injury in these patients. If our results are confirmed by other studies, FibroScan may be regularly used in the management of SCD patients in whom liver is the main target organ of the disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Non Invasive Evaluation of Hepatic Iron Concentration By Fibroscan in Transfusion-Dependent Egyptian Patients with Chronic Hemolytic Anemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1061-1061
Author(s):  
Amal El-Beshlawy ◽  
Dalia Omran ◽  
Hala Mohsen Abdullatif ◽  
Niveen Salama ◽  
Mohamed Ahmed Abdel Naeem ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Iron Overload ◽  
Sensitivity And Specificity ◽  
Transient Elastography ◽  
Iron Concentration ◽  
Hepatic Iron ◽  
Cell Disease ◽  
Non Invasive ◽  
Cutoff Values ◽  
Chronic Hemolytic Anemia

Abstract Background: Transient elastography (Fibroscan®) is an ultrasound technique used to measure liver stiffness (LS), and thus assess for liver fibrosis, in patients with various chronic hepatic disorders. It can also be used to predict severity in multiple other diseases that might affect LS such as amyloidosis and possibly conditions associated with iron overload. Objectives: To assess the frequency of liver fibrosis in patients with chronic hemolytic anemia using Transient elastography (Fibroscan®), and to determine the reliability of this tool as a non-invasive method to predict hepatic iron content as compared to liver iron concentration (LIC) measured by magnetic resonance imaging (MRI). Patients and methods: Seventy-five transfusion dependent patients (50 β-thalassemia major;25 sickle cell disease) with a mean age of 13.4±5.2 years in addition to 75 -age and sex matched- healthy children were recruited. All subjects underwent assessment of LS in kilopascals (kPa), by Transient elastography measurement using FibroScan (Echosens, Paris, France І). Steady state serum ferritin (SF), and hepatitis B serologies (HBsAg and antiHB core antibodies) were assessed by enzyme linked immunoassay (ELISA). LIC values, within 6 months' duration, as identified by quantitative MRI of hepatic iron stores as a signal intensity ratio method based on T1 and T2* contrast imaging without gadolinium were retrieved. Informed consent was obtained from patients' legal guardians prior to enrollment in the study. Results: The median SF was 2280 ng/ml (84% had values exceeding 1000 ng/ml). The median LIC was 13.86 mg/g dw (78.7% patients showed LIC above 7 mg/g dw). The median cardiac T2* was 30.8 ms (3 patients had values below 20). Fifty-two (69.3%) patients were categorized as F0-1 and 21 (28%) were stage F2, 2 (1.3%) were stage F3, and 2 patients had severe fibrosis. The mean and median fibroscan (FS) values were 6.19 ±1.76 kPa and 5.9 kPa (range 3 to 14.1) respectively. Patients had significantly higher mean FS compared to control group (p ˂0.001). Patients with no or mild fibrosis (F0-1) had lower FS values (5.3kPa) compared to patients with fibrosis grades 2-4 (p ˂0.001). FS values were not affected by disease type (thalassemia or sickle cell disease), age (above 12 years), or HCV sero-positivity. FS values correlated with SF (r=0.410, p˂ 0.001). Simple regression analysis of the two variables suggested that changes in SF were associated with minimal but significant changes in FS values (p=0.04) with good agreement (kappa =0.324, p=0.003). LIC did not differ in relation to grade of fibrosis (p>0.05), did not correlate with FS values (r= 0.014, p=0.908), and no changes in FS were expected with LIC changes on regression analysis (p=0.466) with low agreement between LIC and FS at cutoff value 5.3 kPa (kappa = 0.015, p=0.9). Sensitivity and specificity of FS values to predict LIC were high at cutoff values ranging between 3.2 to 3.75 kPa but decreased markedly at higher cutoff values. On comparing sensitivity and specificity of FS values in prediction of iron overload at different cutoff values by ROC curve, it could not significantly predict iron overload (p=0.7). No correlations were found between LIC and other variables including SF (r=0.2), and changes in SF were not significantly associated with changes in LIC values (p =0.089). However, sensitivity and specificity of SF in predicting LIC were good at cutoff 1003.85 ng/ml but decreased markedly at higher cutoff values. Comparing its sensitivity and specificity to that of SF in the prediction of iron overload at different cutoff values by ROC curve, FS could not predict iron overload accurately (p=0.9) and the degree of agreement between these two variables as indicators of iron overload was low (kappa=0.063, p=0.478). Conclusion: Fibroscan could be a valuable tool to assess the degree of liver fibrosis in patients with elevated SF, but it does not appear to reliably predict LIC in such group of patients especially with severe iron overload. FS values were not affected by disease type, age above 12 years, or HCV sero-positivity. Figure Figure. Disclosures No relevant conflicts of interest to declare.

Non-Invasive Monitoring of Hepatic Iron Concentration during Oral Chelation in Patients with Non-Regularly Transfused β-Thalassemia/Hb E Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3615-3615
Author(s):  
Pensri Pootrakul ◽  
Wanida Chua-anusorn ◽  
Adam Fleming ◽  
Paul Clark ◽  
Pornpan Sirankapracha ◽  
...  
Keyword(s):  
Serum Ferritin ◽  
Chelation Therapy ◽  
Measurement Techniques ◽  
Iron Concentration ◽  
Hepatic Iron ◽  
Transverse Relaxation Rate ◽  
Non Invasive ◽  
Hb E ◽  
The Mean ◽  
Hepatic Iron Concentration

Abstract Current non-invasive measurement techniques of hepatic iron concentration (HIC) include magnetic susceptometry (SQUID) and the magnetic resonance imaging (MRI) methods utilising T2 and T2*. HIC can be quantified through image measurement of the proton transverse relaxation rate (R2) (St. Pierre et al Blood 2004). The potential for using the St Pierre method to monitor changes in HIC of patients with β-thalassemia/Hb E undergoing iron chelation therapy was investigated. Seventeen non-tansfusion dependant β-thal/Hb E patients who had not previously undergone chelation were studied. Subjects were chelated with the oral iron chelator Deferiprone (DFP) and had their HIC measured using both the R2-MRI and biopsy non-heme iron techniques pre and post treatment. Ferritin levels were also assayed for comparison. The subjects ages ranged from of 13 to 53 years (mean 31.6, SD 11.5). DFP was administered at a low dose of 50 mg/kg/Day with divided doses 2 –3 times daily. The periods of drug exposure ranged between 53 and 77 weeks (mean 64.1, SD 8.4). HIC by R2-MRI and tissue iron chemical analysis, and serum ferritin Measurement R2-HIC (mg/g DW) Biopsy-HIC (mg/g DW) Serum Ferritin (ng/ml) Mean ± SD Range Mean ± SD Range G.Mean ± SE Range Initial 17.8 ± 6.6 5.7 – 29.7 18.3 ± 9.0 6.0 – 40.1 2526 ± 432 842 – 6072 Final 8.4 ± 7.9 1.0 – 23.9 7.4 ± 7.3 0.2 – 25.5 416 ± 236 113 – 4030 The results show a significant decrease of HIC after long term administration of DFP with MRI and biopsy (p= .0004 and p<0.0001 respectively). Spearman rank correlations of R2-HIC with the liver non-heme Fe and serum ferritin measures gave positive values of 0.866 (p < 0.0001) and 0.768 (p < 0.0001) respectively. The mean reduction of R2-HIC, biopsy-HIC and serum ferritin were 53%, 69%, and 74%, respectively. A decrease of 20.5% (SD ±14.9%) in the standard deviation of the R2 distribution was observed suggesting a decrease in iron heterogeneity accompanied the mean HIC decrease. The results suggest that R2 MRI has the potential to be used as a clinical monitoring tool in chelation therapy.

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