scholarly journals Iron Overload Status in Patients with Non-Transfusion-Dependent Thalassemia in China

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1287-1287
Author(s):  
Rong rong Liu ◽  
Yu mei Huang ◽  
Peng Peng ◽  
Xiao yun Wei ◽  
Yu Lei ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Genetic Disorder ◽  
Chinese Patients ◽  
Beta Thalassemia ◽  
Iron Level ◽  
Liver Iron ◽  
Liver Iron Overload ◽  
Medical University ◽  
Hbh Disease

Abstract Background: Non-transfusion-dependent thalassemia (NTDT) is a genetic disorder most commonly including beta-thalassemia intermedia (Beta-TI), HbE/Beta thalassemia (HbE/Beta thalassemia), and hemoglobin H disease (HbH disease). NTDT patients can be at risk of iron overload due to increased intestinal iron absorption triggered by chronic anemia, ineffective erythropoiesis and, possibly, decreased serum hepcidin. Despite NTDT is popular in southern China, there is little data evaluating iron overload in Chinese patients. This study aimed at investigating the occurrence, prevalence and severity of iron overload in Chinese population with NTDT. Methods: We evaluated the serum ferritin (SF), liver iron concentration (LIC) and cardiac T2* in 158 NTDT patients (83 with HbH disease, 45 with Beta-TI and 30 with HbE/Beta thalassemia) in China. The median age was 22 years old. The main characteristics of these patients along with the main results of the study were summarized in Table 1. Blood samples were obtained for the assessment of hemoglobin (Hb) and serum ferritin (SF) levels. LIC was assessed by using validated R2 magnetic resonance imaging [MRI] (FerriScan®). Cardiac iron level was measured by MRI T2*. Patients were scanned with MRI 1.5 T (Siemens Avanto, Germany). The study was performed at the First Affiliated Hospital of Guangxi Medical University. LIC < 3mg Fe/g dw and cardiac T2* > 20ms was considered normal. Abnormal LIC can be divided into mild: 3-7mg Fe/g dw, moderate: 7-15mg Fe/g dw, severe: >15mg Fe/g dw. All patients or parents/guardians provided their written informed consent to participate in this study. The study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University. Results: The median SF level of 158 NTDT patients was 1,037(27.0-19,704) ng/ ml. LIC was detected in 155 patients (98.1%) and the median LIC value was 8.9(0.6-43) mg Fe/g dw. There were 15 patients (60%) (8 with HbH disease, 5 with Beta-TI and 2 with HbE/Beta thalassemia)<10 years old found liver iron overload. The youngest patient with liver iron overload was 5 years old with 5.6mg Fe/g dw in LIC. Cardiac T2*was assessed in 111 patients (70.2%) and the median cardiac T2* was 32.8(7.5-75.1)ms. The 7 patients (4.4%) (4 with HbH disease and 3 with Beta-TI) had cardiac T2*=<20ms. There was a significant correlation between LIC and SF (r=0.809, p<0.001). No correlation between LIC and Hb, cardiac T2* values can be verified. There was a significant correlation between LIC and age (r=0.497, p<0.001)(Fig 1). The levels of LIC in patients > 30-year old group are significantly higher than those in other groups (Fig 2).The patients with Beta-TI and HbE/Beta thalassemia showed a statistically significant lower Hb and higher values of SF and LIC than those of HbH disease patients. Conclusions: Chinese NTDT patients have a high prevalence of iron overload. The iron overload in patients with Beta-TI and HbE/Beta thalassemia are more serious than those in HbH disease patients. The age of patient is a risk factor of iron overload in NTDT patient. Patients > 30 years old have a high burden of iron overload. Our data shows that the first assessment of MRI LIC should be performed as early as 5 years old. Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical-Pathological Features of Non-Transfusion Dependent Thalassemia in Adults — a Single Center Study in Hong Kong

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4900-4900
Author(s):  
Ka Lok Luke Chan ◽  
Vivien W M Mak ◽  
Kate F S Leung ◽  
Joyce H Y Kwong ◽  
Nelson C N Chan ◽  
...  
Keyword(s):  
Hong Kong ◽  
Liver Fibrosis ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Transfusion Requirement ◽  
Liver Stiffness ◽  
Leg Ulcer ◽  
Liver Iron ◽  
Liver Iron Overload ◽  
Hbh Disease

Abstract Introduction: Non-transfusion dependent thalassemia (NTDT) includes HbH disease, β-thalassemia intermedia (β-TI) and HbE/β-thalassemia. The transfusion requirements of patients with NTDT are variable and they are all at risk of developing iron overload and other complications. The prevalent genetic changes in thalassemia are different across geographical territories, accounting largely for the diverse clinical outcomes. The complication profile of NTDT in Southern China is less well studied than other areas. Data on age-related complications is sparse. The present study aims to describe the clinical-pathological features of adult NTDT patients in Hong Kong, and to evaluate the risk factors associated with complications. Method: A single-center observational study was performed during Jan 2017 to Jun 2018. Data collection included review of medical records for demographics; globin genotypes; hepatitis B and C status; transfusion requirement; splenectomy; iron chelation therapy; complications including gallstone disease, hypothyroidism or hypogonadism, diabetes mellitus (DM), extramedullary hematopoiesis (EMH), leg ulcer, venous thrombosis and cerebral ischemia. During the study period, steady state hemoglobin (Hb) and serum ferritin levels in the recent year were obtained; organ iron deposition assessed using liver and cardiac T2* at 1.5T MRI; liver stiffness measured by Fibroscan; and presence of pulmonary arterial hypertension (PAH) evaluated by echocardiography. The disease profile and prevalence of complications were described with descriptive statistics. Factors impacting clinical parameters and development of complication were studied with univariate regressions. Age and sex adjusted β-coefficients or odd ratios were then determined with multivariable regression analysis. Results: A total of 96 Chinese patients were recruited (mean age 50±15 years; 31% patients >60 years; females 66%). There were 63 (65%) patients having deletional HbH disease, 20 (21%) with non-deletional HbH disease (ND-HbHD), and 13 (14%) with β-TI. The mean Hb was 8.9±1.1 g/dL. Transfusion requirement was never in 39 (41%), occasional in 50 (52%), and regular in 7 (7%) patients. Ten (10%) patients were splenectomized. Iron chelation was given to 21 (21%) patients and the median duration of therapy was 3 (range 1-21) years. Respectively 4 (4%) and 2 (2%) patients were hepatitis B and C carriers. The median serum ferritin was 473 [IQR 217-1029] ng/mL. The median liver iron concentration (LIC) estimated by MRI T2* was 3.6 [IQR 1.7-7.1] mg Fe/g with 26% of patients having moderate to severe liver iron overload (≥7.1 Fe mg/g). In the study population, the prevalence of liver fibrosis (liver stiffness ≥7.1kPa) was 26%, gallstones 50%, hypo-thyroidism/-gonadism 8%, DM 16%, EMH 5%, leg ulcer 1%, thrombotic events 2%, cardiac iron overload 1%. No patients had PAH (Table 1). In multivariable regression, advanced age (>60 years) was associated with lower Hb (p=0.03), higher risk of liver fibrosis (p=0.04) and DM (p<0.01). β-TI was associated with higher transfusion requirement (p<0.01), higher serum ferritin (p<0.01) and higher risk of hypo-thyroidism/-gonadism(p=0.01). Both ND-HbHD and β-TI were associated with higher LIC (p<0.01). Patients requiring regular transfusions had higher serum ferritin (p<0.01) and LIC (p<0.01). Occasionally transfused (p=0.01) and female patients (p=0.01) had higher risk of developing gallstones. Splenectomy was associated with higher serum ferritin level (p=0.03). Patients with moderate to severe liver iron overload had increased risk of liver fibrosis (p=0.01) (Table 2). Conclusions: The present study including 1/3 of elderly patients illustrates the heterogeneous clinical features of NTDT in Hong Kong in terms of transfusion requirement and body iron store. HbH disease is the most frequent type of NTDT. Liver iron overload, liver fibrosis, gallstones and DM were the most common complications. Advancing age, β-TI, ND-HbHD were associated with higher risk of developing complications. A low prevalence of EMH, cardiac iron overload, PAH, thrombosis and leg ulcer was observed. Larger prospective study is needed to confirm the prevalence of complications in NTDT in Chinese, which may be different from other ethnic groups, and at the same time to provide more insight to the pathophysiology of NTDT and facilitate establishment of future local management strategies. Disclosures No relevant conflicts of interest to declare.

Does Gene Therapy in Beta Thalassemia Normalize Novel Markers of Ineffective Erythropoiesis and Iron Homeostasis?

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 816-816 ◽  
Author(s):  
Alexis A. Thompson ◽  
Tomas Ganz ◽  
Mary Therese Forsyth ◽  
Elizabeta Nemeth ◽  
Sherif M. Badawy
Keyword(s):  
Gene Therapy ◽  
Stem Cell ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Research Funding ◽  
Iron Homeostasis ◽  
Beta Thalassemia ◽  
Ineffective Erythropoiesis ◽  
Liver Iron ◽  
Equity Ownership

BACKGROUND: Ineffective erythropoiesis in thalassemia alters iron homeostasis, predisposing to systemic iron overload. Successful allogeneic hematopoietic stem cell transplantation (HSCT) in thalassemia major corrects anemia, should eliminate ineffective erythropoiesis (IE) and normalize iron homeostasis (IH). Whether gene therapy (GT) will fully correct IE and IH is not known. This cross-sectional observational study evaluated the iron status of patients with beta thalassemia following HSCT or GT, and compared them with cohorts of patients with thalassemia intermedia (TI) or transfusion-dependent thalassemia (TDT) using recently introduced biomarkers along with imaging studies and other clinical assessments to better understand and characterize IE and IH across groups. METHODS: We evaluated a convenience sample of 29 participants with beta thalassemia (median age 25 years, IQR 21-35; females 55%; Asian 52%). Participants in the HSCT (n=6) and GT (n=10) groups were evaluated on average 116.5 and 46.9 months following cell infusion, respectively. TDT patients (n= 9) were evaluated pre-transfusion and off iron chelation for at least 7 days, and TI (n=4) were un-transfused or not transfused in &gt;3 years. Clinical lab assessments and MRI R2*/ T2* to assess heart and liver iron burden including post-processing, were performed using local clinical protocols. ELISAs for hepcidin, erythroferrone (Erfe) and GDF-15 were performed in a blinded manner. RESULTS: Median values for all IE and IH parameters tested were normal in the HSCT group, and were significantly lower than in all other groups. There were significant differences among all groups for hemoglobin (p=0.003), erythropoietin (Epo) (p=0.03), serum ferritin (SF) (p=0.01), transferrin (p=0.006), soluble transferrin receptor (sTfR) (p=0.02), serum hepcidin: serum ferritin (H:F) ratio (p=0.006), Erfe (p=0.001), GDF15 (p=0.003), and liver iron content (LIC) by MRI R2* (p=0.02). H:F ratio, a surrogate for predisposition to systemic iron loading, inversely correlated with Erfe (rs= -0.85, p&lt;0.0001), GDF15 (rs= -0.69, p=0.0001) and liver R2* (rs= -0.66, p=0.0004). In a multivariate analysis, adjusted for gender and race, H:F ratio and Epo levels predicted Erfe and GDF15 (p=0.05 and p=0.06; p=0.01 and p=0.05), respectively. Even after excluding GT patients that are not transfusion independent (N=2), SF, Epo, sTfR and hepcidin remain abnormal in the GT group, and there were no significant differences in these parameters between GT and TDT. However, novel biomarkers of IH and IE suggested lower ineffective erythropoiesis in GT compared to TDT (median (IQR) Erfe, 12 (11.6-25.2) vs. 39.6 (24.5-54.7), p=0.03; GDF15, 1909.9 (1389-4431) vs. 8906 (4421-12331), p=0.02), respectively. Erfe and GDF15 were also lower in GT compared to TI, however these differences did not reach statistical significance. There were no differences in hepcidin, ferritin, or H:F by race, however Erfe and GDF15 were significantly lower in Asians compared to non-Asians (p=0.006 and p=0.02, respectively). CONCLUSION: Nearly 4 years post infusion, most subjects with TDT treated with GT are transfusion independent with near normal hemoglobin, however, studies in this limited cohort using conventional measures suggest IE and IH improve, particularly when transfusion support is no longer needed, however they remain abnormal compared to HSCT recipients, who using these parameters appear to be cured. STfR did not detect differences, however GDF15 and Erfe were more sensitive assays that could demonstrate significant improvement in IE and IH with GT compared to TDT. Contribution to IE by uncorrected stem cell populations post GT cannot be determined. Transduction enhancement and other recent improvements to GT may yield different results. Longitudinal studies are needed to determine if thalassemia patients treated with GT will have ongoing IE predisposing to systemic iron overload. Disclosures Thompson: bluebird bio, Inc.: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Baxalta: Research Funding. Ganz:Intrinsic LifeSciences: Consultancy, Equity Ownership. Nemeth:Intrinsic LifeSciences: Consultancy, Equity Ownership; Silarus Therapeutics: Consultancy, Equity Ownership; Keryx: Consultancy; Ionis Pharmaceuticals: Consultancy; La Jolla Pharma: Consultancy; Protagonist: Consultancy.

scholarly journals Correlation between serum ferritin level, cardiac and hepatic T2-star MRI in patients with β-thalassemia major in Al-Diwaniya thalassemia center

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Alaa Mutter Jabur Al-Shibany ◽  
AalanHadi AL-Zamili
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Chelation Therapy ◽  
Ferritin Level ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Iron Level ◽  
The Mean ◽  
T2 Mri

Patients with transfusion dependent thalassemia major is often associated with iron overload. Proper use of iron chelators to treat iron overload requires an accurate measurement of iron levels. Magnetic resonance T2-star (T2* MRI) is the preferred method to measure iron level in the liver andthe heart. The goal of our study was to see if there is an association exists between serum ferritin level and T2* MRI results in patients with beta thalassemia major.This study was done in Al-Diwaniya Thalassemia center,Maternity and children teaching hospital,Iraq. During the period from 1st of January to 31st of October. Fifty eight patients with a diagnosis of beta thalassemia major were enrolled in the study. They were older than five years old,transfusion dependent and on chelation therapy. Hepatic and Myocardial T2*MRI and the mean serum ferritin levels were measured during the study period for all patients.There is a significant correlation was observed between serum ferritin level and cardiac T2*MRI (p=0.018 ). also a significant correlation was observed between serum ferritin and hepatic T2*MRI (p=0.02). Neither cardiac T2* MRI nor hepatic T2* MRI show any correlation with the mean age.our study also showa positive correlation between the patients withcardiac T2* MRI and the development of diabetes mellitus in contrast to hepatic T2* MRI in which there is no any correlation. Hypothyroidism was observedno correlation with either cardiac or hepatic T2* MRI.Our results showed a positiveassociation between hepatic, cardiac T2*MRI and serum ferritin levels.

Deferasirox Safety Profile in Patients with Transfusion-Dependent Anaemias:Results From the Interim Analysis of a Hellenic Study,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3183-3183
Author(s):  
Vassilis Ladis ◽  
Marouso Drossou ◽  
Dimitria Vini ◽  
Ersi Voskaridou ◽  
Miranda Athanasiou-Metaxa ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Safety Profile ◽  
Interim Analysis ◽  
Pediatric Patients ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Liver Iron ◽  
Liver Iron Overload

Abstract Abstract 3183 Background: The introduction of iron chelation treatment has led to a significant improvement in morbidity and overall survival in patients with transfusion-dependent anemias. Deferasirox is a once-daily, oral iron chelator approved for the treatment of transfusional iron overload in both adult and pediatric patients. The efficacy and safety of deferasirox in a variety of transfusion-dependent anemias has been established in numerous Phase II/III clinical trials. Since most patients with transfusion-dependent anemias require lifelong iron chelation therapy, there is a need to assess the long-term safety of deferasirox in both adult and pediatric patients. Aim: To assess the safety profile of deferasirox in patients with transfusional iron overload in a real-world clinical setting. To further investigate the safety profile of deferasirox in patients with congenital erythrocyte disorders and transfusional iron overload, with ferritin levels <4000 ng/ml and without severe cardiac siderosis. Methods: Between July 2009 and September 2010, 85 patients with transfusion-induced iron overload treated with deferasirox as per the approved product labeling were enrolled in the study. These data represent the 24-week planned interim analysis of a 12-month observational study on deferasirox safety profile in the treatment of pediatric and adult patients with transfusion-dependent anemias who were newly-treated with deferasirox. Safety was evaluated through the monitoring and recording of all adverse events and serious adverse events, as well as routine laboratory testing, including hematology, blood chemistry and hepatic function assessments. Results: The population had a median age of 37.6 years (range: 5.3–61.4) and a female to male ratio of 1.3. Beta-thalassemia (67.1%) was the most common transfusion-dependent anemia, followed by thalassemia intermedia requiring periodic transfusions (20.0%) and sickle cell anemia (12.9%). Mean baseline ferritin levels were 1502.1±870.5 (pediatric group: 1480.2±522.8 and adult group: 1503.6±891.4), while 53 out of the 85 patients (62.4%) had serum ferritin level above 1000 ng/ml. Mean baseline liver T2* value was 10.4±9.7 ms; 44.4% of patients demonstrated minimal liver iron deposition (MRI T2* > 6.3 ms), 51.4% had mild to moderate liver iron overload (T2* ≤ 6.3 ms), and 4.2% had severe liver iron overload (T2*<1.4 ms). 54 (63.5%) of patients analysed had been pre-treated with iron chelators and 31 (36.5%) were chelation-naïve. The initial average daily dose of deferasirox was 25.9±4.8 mg/kg, and 70.6% of patients had no dose modification during the 24-week follow-up period. A statistical significant decrease in median serum ferritin levels was observed by Week 24 (mean absolute change from baseline:-214.5 ng/mL; p=0.009) [Figure 1]. No statistically significant changes were observed in creatitine levels, creatinine clearance and transaminases by Week 24 [Figure 1]. 37 ADRs were reported by 17 patients (20%) over the 24-week period. Among the most frequently observed ADRs (>5%) were epigastralgia reported by 7.1% of patients (6/85) and loose stools/diarrhoea by 5.9% of patients (5/85). The majority of ADRs reported (nevents=25; 67.6%) were graded as mild in severity, while 21.6% (nevents=8) were graded as moderate and 10.8% (nevents=4) as severe. Most ADRs (nevents=31; 83.8%) resulted in full recovery by Week 24. The overall incidence of SADRs was as low as 1.2% (in particular one patient experienced severe epigastralgia and upper extremity pain which resulted in her withdrawal from the study after four months of treatment). The all-cause discontinuation rate was 9.4% (8/85), while only two patients (2.4%) discontinued the study therapy due to ADR; 1 patient due to increased transaminase levels and 1 patient due to the aforementioned SADR. Conclusions: These data highlight the safety profile of deferasirox in both adult and pediatric patients; the regular monitoring of serum ferritin levels as well as other iron-overload parameters and transfusion requirements play a major role in determining and optimizing the outcome of iron chelation therapy. Disclosures: Ladis: Novartis Hellas S.A.C.I.: Investigator participating in a trial sponsored by Novartis. Drossou:Novartis Pharmaceuticals: Investigator participating in a trial sponsored by Novartis. Vini:Novartis Pharmaceuticals: Investigator participating in a trial sponsored by Novartis. Athanasiou-Metaxa:Novartis Hellas S.A.C.I.: Research Funding. Oikonomou:Novartis Hellas S.A.C.I.: Investigator participating in a trial sponsored by Novartis. Vlachaki:Novartis Hellas S.A.C.I.: Investigator participating in a trial sponsored by Novartis. Tigka:Novartis Hellas S.A.C.I.: Employment. Tzavelas:Novartis Hellas S.A.C.I.: Employment. Liakopoulou:Novartis Hellas S.A.C.I.: Investigator participating in a trial sponsored by Novartis. Adamopoulos:Novartis Hellas S.A.C.I.: Investigator participating in a trial sponsored by Novartis. Kattamis:Novartis Hellas S.A.C.I.: Honoraria, Membership on an entity's Board of Directors or advisory committees.

The Effect of Combination Iron Chelating Agents on Reducing the Severity Grading of Heart and Liver Iron Overload in β-Thalassemia Patients

2019 ◽  
Author(s):  
Majid Ghanavat ◽  
Alireza Fazeli Varzaneh ◽  
Nahid Reisi
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Ferritin Level ◽  
Iron Deposition ◽  
Liver Iron ◽  
Liver Iron Overload ◽  
Severity Grading ◽  
Group A ◽  
Group B

Background: Deferasirox (DFX), Deferoxamine (DFO), and Deferiprone (DFP) are iron chelators that can be used in thalassemic patients with iron overload. Materials and Methods: This clinical trial was performed on 108 thalassemic patients who were randomly divided into group A (n=54) and B (n=54). Group A received combination of DFX and DFP, and group B received DFO and DFP for six months. Serum ferritin level was measured at the beginning of the study, 3, and 6 months after the treatment; The heart and liver iron deposition rates were also measured at the beginning of the study, and 6 months after the treatment  in both groups and compared using Magnetic Resonance Imaging T2 plus (MRI T2*). Results: The mean age of patients in group A and B was 17.29±4.3 and 17.89±5.61 years old, respectively. Serum ferritin level significantly reduced after the treatment (Serum ferritin level at baseline, 3, and 6 months after the treatment in Group A: 2476.25±1289.32, 2089.62±1051.64 and 1290.22±724.78 ng/ml, respectively; in Group B: 2044.63±989.82, 1341.30±887.62 and 1229.41±701.22 ng/ml, respectively) (p<0.01, for both groups). MRI T2* heart and liver was also improved at the end of the study in both groups (p<0.01, for both groups). However, the combination of DFO/DFP significantly decreased severity grades of liver iron deposition in comparison to DFX/DFP regimen after six months (p<0.01). Conclusion: The results of the present study indicated that both combination therapies of DFO/DFP and DFX/DFP could improve heart and liver MRI T2*. However, DFO/DFP combination therapy was more effective in reducing the severity grades of liver iron deposition.     

scholarly journals Serum ferritin in the diagnosis of cardiac and liver iron overload in thalassaemia patients real-world practice: a multicentre study

2017 ◽  
Vol 182 (2) ◽  
pp. 301-305 ◽  
Author(s):  
Rungroj Krittayaphong ◽  
Vip Viprakasit ◽  
Pairash Saiviroonporn ◽  
Wipaporn Wangworatrakul ◽  
John C. Wood
Keyword(s):  
Multicentre Study ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Real World ◽  
Liver Iron ◽  
Liver Iron Overload

R* Magnetic Resonance Imaging (MRI) of the Liver for Patients with Iron Overload.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2670-2670
Author(s):  
Jane S. Hankins ◽  
M. Beth McCarville ◽  
Ralph Loeffler ◽  
Ruitian Song ◽  
Russell E. Ware ◽  
...  
Keyword(s):  
Liver Biopsy ◽  
Iron Overload ◽  
Correlation Coefficient ◽  
Serum Ferritin ◽  
Iron Content ◽  
Bone Marrow Failure ◽  
Correlation Coefficients ◽  
Beta Thalassemia ◽  
Liver Iron ◽  
Hematological Diseases

Abstract Iron overload is an inevitable consequence of multiple transfusions and occurs in many hematological diseases including sickle cell anemia (SCA) and beta thalassemia (β-thal). Liver biopsy provides quantification of iron content in the liver, but is not without risks such as bleeding, pain, and infection. MRI R2* has the advantage of quantifying liver iron without the risks of invasive procedures, however, this technique has not been fully investigated or validated. Furthermore, the variability introduced by multiple MRI readers has not been investigated to date. Patients with hematological diseases were selected to participate in this prospective IRB-approved study if they received ≥ 18 transfusions or had a serum ferritin ≥ 1000 ng/mL. All study participants completed 1.5 Tesla MRI R2* testing (Siemens Symphony), serum ferritin, and liver biopsy with quantification of liver iron content (LIC) within 30 days. Regions of interest (ROI) were drawn on R2* maps in a homogeneous area of the right hepatic lobe, avoiding blood vessels and obvious bile ducts. Three independent reviewers, blinded to the patients’ clinical status and the other 2 reviewers’ results, performed the ROI analysis. The correlation between LIC and liver R2* was calculated using the Spearman’s Rank-Order Correlation Coefficient. Due to possible outliers in the data, robust simple linear regression methods were used to fit a regression line to scatter plots. All liver biopsy samples were sent to Mayo Laboratories for LIC quantification. The agreement among the 3 raters was assessed using the interclass correlation coefficient (ICC). Forty-seven patients, median age 14 years (range 7 – 37) participated; 24 were female. Thirty-five of them had SCA, 8 had β-thal (major or intermedia), and 4 had bone marrow failure syndromes. Total table time for R2* MRI testing was between 20 to 30 minutes. All patients tolerated the liver biopsy without complications. The mean (±1SD) ferritin was 2917ng/mL (±2239), mean LIC was 12.139 mg/ 100g of dry weight liver (±8.269), and mean liver R2* ranged from 425 to 432 Hz (±257 to 249 Hz). All 3 raters produced R2* values strongly associated with LIC, with correlation coefficients from 0.93 to 0.95 (p&lt;0.00005). There was a significant positive association between serum ferritin and R2* liver values (correlation among the 3 reviewers ranged from 0.39 to 0.50 with all p&lt;0.009). The agreement among the 3 raters was 0.98. To summarize: 1) 1.5 T MRI R2* liver values are highly associated with LIC in patients with iron overload. This is the largest sample of MRI R2* liver measurements correlated with LIC obtained by liver biopsy; 2) The three raters had excellent agreement which suggests that, in our study, R2* liver values do not differ greatly among qualified readers; 3) R2* measurements of the liver were significantly associated with serum ferritin, however, the correlation coefficients were relatively low (0.39 to 0.50), documenting a weak relationship; and 4) MRI R2* of the liver is a feasible and valid technique to assess LIC non-invasively, and appears to be reproducible when performed by qualified reviewers. We conclude that liver MRI R2* can be incorporated into clinical research protocols for safe, painless, and accurate liver iron quantitation.

scholarly journals Liver iron overload and hepatic function in children with thalassemia major

2018 ◽  
Vol 58 (5) ◽  
pp. 233-7
Author(s):  
Pustika Amalia Wahidiyat ◽  
Stephen Diah Iskandar ◽  
Ludi Dhyani Rahmartani ◽  
Damayanti Sekarsari
Keyword(s):  
Iron Overload ◽  
Correlation Coefficients ◽  
Normal Liver ◽  
Thalassemia Major ◽  
Hepatic Function ◽  
Iron Level ◽  
Liver Iron ◽  
Cross Sectional ◽  
Liver Iron Overload ◽  
T2 Mri

Background Routine blood transfusions and increased intestinal iron absorption lead to iron accumulation in various organs, especially the liver. To date, T2-star magnetic resonance imaging (T2*MRI) is a valuable tool to evaluate iron level in organs. Objective To assess the degree of liver iron overload among children with thalassemia major (TM) and its possible correlations with hepatic function laboratory values. Methods This cross-sectional study was conducted in Cipto Mangunkusumo Hospital. The degree of liver iron overload was evaluated by T2*MRI. Assessments of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, and bilirubin levels were done to evaluate liver function. Results A total of 291 TM children were included in this study. The mean age of subjects was 12 years. Most of the subjects were diagnosed as β-thalassemia homozygote (54.6%) and β-thalassemia/HbE (41.2%). Deferiprone (DFP) was the most commonly used iron chelator. Less than 10% of the subjects had normal liver iron deposition. The AST and ALT values increased proportionally with the severity of liver iron overload, with significant, moderately negative correlation coefficients (r=-0.388 and -0.434, respectively). However, albumin level decreased proportionally with the severity of liver iron overload, with a significant, moderately positive correlation coefficient (r=0.323). Liver T2* MRI had no significant correlations with direct, indirect, and ratio of direct/total bilirubin levels. Conclusion Most of the children with TM have mild to severe liver iron overload. Liver T2* MRI had significant, moderate correlations with AST, ALT, and albumin values. Bilirubin level has no correlation with T2* MRI. Our findings suggest that monitoring of AST, ALT, and albumin levels is important because they may reflect the severity of liver iron overload. However, they should not be used as the only predictors of iron overload.

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