Liver Fibrosis in Adult Thalassemia Patients Assessed by Transient Elastography.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3820-3820
Author(s):  
Elena Cassinerio ◽  
Mirella Fraquelli ◽  
Elisabetta Volpato ◽  
Cristina Rigamonti ◽  
Massimo Colombo ◽  
...  
Keyword(s):  
Iron Overload ◽  
Transient Elastography ◽  
Thalassemia Major ◽  
Hcv Rna ◽  
Liver Iron ◽  
Non Invasive ◽  
Group I ◽  
Group Ii ◽  
T2 Mri ◽  
Severe Fibrosis

Abstract Background and aim. Transient elastography (TE) is a new, non-invasive and reproducible technique that measures liver stiffness (LSM). It has been demonstrated to be a reliable tool for assessing hepatic fibrosis and cirrhosis in patients with chronic liver disease (CLD). However, its role in patients with b- thalassemia has not been extensively investigated. The aim of the present study was to assess LSM and its possible correlation with iron overload in HCV positive patients with b- thalassemia major and intermedia. Methods. During a six-month period (from January to June 2007) 46 consecutive adults patients with b- thalassemia afferring to a single Italian Thalassemia Care Center in Milan, Italy, were enrolled in the study. Twenty-nine patients (Group I: 7 M and 23 F; mean age 31±SD 7.1 yrs; mean BMI 23.4±SD 3 Kg/m2) had b- thalassemia major and 17 intermedia (Group II: 10 M and 7 F; mean age 43±SD12.4 yrs; BMI 22 ±SD 3 Kg/m2). Sixteen patients (55%) in group I and two (12%) in group II were HCV RNA positive. All patients were examined by TE (FibroScan®; Echosens, Paris, France) and only the examinations with at least 10 validated measurements and a success rate of at least 60% were considered adequate. According to a previous study in CLD patients the considered TE cut off to diagnosing different stages of hepatic fibrosis were: >7.9 kPa for F≥2; >10.3 for ≥F3 and >11.9 for F=4. Twelve patients (all in group I) also had undergone liver biopsy. Necroinflammation and fibrosis were scored by METAVIR classification; liver iron concentration (LIC, mg/gr of liver dry weight) was measured on fresh tissue cores by atomic absorption spectrometry. Twenty-five patients underwent liver iron determination by T2* Magnetic Resonance Imaging (MRI) assessment. Results. In patients who underwent liver biopsy, LSM increased proportionally to the METAVIR stage and a significant positive correlation was observed between LSM and fibrosis stage (r=0.57, p= 0.039). Patients in group I had significantly higher values of mean LSM values (10.6± SD 9.3 kPa) and serum ferritin (SF) (1367±SD 1169 ng/mL) than those in group II (6.0± SD 3.3 kPa and 716±SD 472 ng/mL, respectively) (p<0.05). In both groups LSM did not significantly correlate with age, BMI, platelets count, serum iron and iron overload measured by T2* MRI. In group I a significant positive correlation was observed betweeen LSM and SF (r=0.47, p=0.008), ALT (r=0.87, p=0.0001) and GGT levels (r=0.80, p=0.0001). Among patients with b- thalassemia major LSM values did not differ significantly between HCV RNA positive (13.0±SD 12.5 kPa) and negative patients (7.7±SD 3.3 kPa) (p=NS) as well as the proportion of patients with significant (F>=2) or severe fibrosis (F>=3) did not differ significantly according to HCV viremic status. Conclusion TE is a reliable non invasive technique to stage liver fibrosis in patients with b- thalassemia major. In these patients with concomitant HCV infection a significant or severe fibrosis was observed in about one third of the cases. Apart from fibrosis also serum necroinflammatory activity, GGT levels and SF levels may influence LSM values. The reliability of liver iron overload by T2* MRI evaluation remains still to be validated.

Non Invasive Assessment of Hepatic Fibrosis by Measurement of Liver Stiffness in Post Transfusional Iron Overload: Preliminary Results in 15 Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3740-3740
Author(s):  
T. Mirault ◽  
D. Lucidarme ◽  
B. Turlin ◽  
Y. Deugnier ◽  
P. Brissot ◽  
...  
Keyword(s):  
At Risk ◽  
Liver Fibrosis ◽  
Iron Overload ◽  
Predictive Value ◽  
Liver Stiffness ◽  
Liver Iron ◽  
Preliminary Results ◽  
Non Invasive ◽  
Patients At Risk ◽  
Severe Fibrosis

Abstract Background: The prognosis of liver iron overload is highly dependent on liver iron content (LIC) and the extent of liver fibrosis. Liver biopsy is the invasive reference method for fibrosis evaluation but with several limitations. Non-invasive biological methods (FibroTest, APRI) are not applicable in blood diseases. Transient elastography (TE) is a new non-invasive and rapid bedside method used to measure liver stiffness.This technique has been extensively studied with success in evaluation of liver fibrosis in HCV infection (Ziol, Hepatology 2005; Castera, Gastroenterology 2005). Until now, no data are available on evaluation of liver fibrosis by TE in highly transfused patients with iron overload. Methods: We assessed liver stiffness (kPa) by elastography measurement (Fibroscan; Echosens, Paris, France). Ishak’s and Metavir’s scales were used to stage fibrosis and hepatitis activity; LIC was measured by atomic absorption spectometry in a central laboratory (Rennes, France) and by MRI procedure according to Gandon (Lancet 2004). Cardiac MRI T2* (indirect estimation of iron heart content) was also measured by MRI according to Anderson (Eur Heart J 2001). Serum ferritin level and HCV serology were assayed in all cases. Correlation statistical analysis used Spearman’s Rho and Pearson tests and mean comparisons were done by a non-parametric Mann-Whitney test. Results: 15 liver samples (weight >1mg except 1) from monthly transfused patients (13 major beta Thalassemia, 1 sickle cell disease, 1 myelodysplastic syndrome) were analyzed. Median age was 37 years (7–75). Histological results were: 3 cirrhosis (METAVIR F=4 (F4), or Ishak’s Staging =6 (IS6)) among 5 patients with severe fibrosis (F3,F4) or (IS4-6) and 10 patients with no or mild fibrosis (F0-2) or (IS0-3). Mean ferritin was 2579 ng/ml CI 95% [1372–3786]. 2 patients were HCV positive. Correlation between LIC and ferritin was 0.82 (p<0,05); between LIC and MRI LIC: 0.88 (p<0,05); LIC and MRI Heart T2*: 0.72(p<0,05); METAVIR F score and Ishak’s grading score: 0.86 (p<0,05). A correlation was also observed between METAVIR F and elastography: 0.60(p<0,05); and mean values of elastography were significally different in patients with severe fibrosis: 9.1kPa CI95% [4.5–13.7] vs 5.9kPa CI95% [4.6–7.2] in those without sever fibrosis (p<0,05) (fig). A value of elastography above 6.25kPa (Se=80%; Sp=70%; AUROC=0.820) identified patients at risk for severe fibrosis (F3,F4 or IS 4–6) (Negative Predictive Value = 88%; Positive Predictive Value = 57%). Conclusion: A significant correlation between Metavir Fibrosis scale and elastography values was found. This new non-invasive method would be helpful to evaluate liver fibrosis and to determine patients who could avoid invasive procedures in particular in regularly transfused low risk myelodysplastic patients at risk of bleeding due to abnormal platelet function. These preliminary results will have to be confirmed in a larger population. Figure Figure

Transient Elastography May Predict Liver Iron Overload in Adult Thalassaemia Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5407-5407 ◽  
Author(s):  
Vasilios Perifanis ◽  
Efthimia Vlachaki ◽  
Emmanouil Sinakos ◽  
Ioanna Tsatra ◽  
Maria Raptopoulou-Gigi ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Iron Overload ◽  
Hepatic Fibrosis ◽  
Transient Elastography ◽  
Iron Concentration ◽  
Thalassaemia Major ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Liver Iron Overload ◽  
T2 Mri

Abstract Although it is life saving, transfusion therapy has resulted in the majority of thalassemia patients being at risk for hemosiderosis-induced organ damage. Liver Iron Concentration (LIC) assessed by liver biopsy is considered the most accurate and sensitive method for determining body iron burden in patients with iron overload. The development of liver fibrosis is more closely related to liver iron concentration. Transient elastography (FibroScan, FS), which measures liver stiffness (LS), is a novel, noninvasive method to assess liver fibrosis. Whether FS is useful in the detection of preexisting liver iron overload in patients presenting with thalassaemia major without chronic viral hepatitis, is unclear. On the other hand, Magnetic Resonance Imaging (MRI) is a relatively inexpensive, widely available but more time consuming method that has long been considered as a useful tool for the non-invasive estimation of tissue iron content in multiple transfused patients with thalassemia. Aim: To study the prevalence and severity of liver fibrosis of transfusion dependent thalassaemia major patients, and correlate the MRI.LIC with the measurements of FS. Methods-Patients: The applicability for FS (Echosens, Paris, France) was defined as at least 10 valid measures and a success rate (number of valid measures/total number of LS Measures, LSM) ≥60% and a ratio of interquartile range/stiffness ≤0,2. Most subjects with FS scores below 5.1 kilopascals (kPa) are considered to have minimal fibrosis (grade F0 or F1, METAVIR score) according to the literature. The cut off FS values for diagnosing different stages of hepatic fibrosis were defined as &gt; 7.9kPa for F≥2, &gt; 10.3kPa for F≥3 and &gt; 11.9kPa for F=4. A total of 43 thalassaemic patients 23 males/20 females, median age 26,8±4,9 years, regularly transfused (pre-transfusion haemoglobin 9,7g/dl) were included in the study. All patients were hepatitis C virus (HCV) negative and chelated with different drugs (13 on deferasirox, 12 on deferiprone, 5 on desferrioxamine and 13 on combined therapy). Median ferritin levels were 1552±1576ng/ml. Liver tests (AST, ALT, γGT and Alkaline Phosphatase) were done simultaneously to all patients. Twenty-two of the 43 patients underwent liver iron determination (LIC) simultaneously by two methods: T2* Magnetic Imaging (T2*MRI) assessment and by calculation of MR-Hepatic Iron Concentration (MR.HIC) values (based on an algorithm developed by Gandon et al (Lancet 2004), using liver to muscle ratios in five axial gradient-echo sequences). T-test was used in statistical analysis to compare means. Results: Applicability of LSM was 100%. Overall median LSM was 8,25±6,05kPa (range 4–40,3kPa). Nineteen (44,1%) patients had FS&lt;6,1kPa (notably 8/19 patients below 5,1kPa), 13 (30,2%) had &lt;7,9kPa, 4 (9,3%) had &lt;10,3kPa, 2 (4,7%) had &lt;11,9kPa and 5 (11,7%) above 11,9kPa. Total FS correlated with Ferritin (r=0,39, p=0,008). Using the cutt-off value of 6,1 kPa for FS measurements, patients were divided in two groups with different ferritin levels: A (&lt;6,1kPa) 1039±758ng/ml vs B (&gt;6,1kPa) 1833±1742ng/ml, p&lt;0,03. FS values of the three different major therapy groups did not differ significantly. FS (22pts) correlated negatively with T2*MRI results (r=−0,39, p=0,07) and positively with MR.HIC results (r=0,49, p=0,02). There was no correlation with liver function tests. Conclusions: Severe haemosiderosis and hepatic fibrosis are common in patients with thalassaemia major despite the use of chelation therapy and the absence of HCV. Elastography has several characteristics that make it a desirable method for assessing hepatic fibrosis. In addition to being noninvasive and painless, it is also quick, inexpensive, and produces consistent results. It can also be useful as an alternative to check for liver iron overload, as abnormal results predict heavy liver iron overload. Further longitudinal and prospective studies are necessary to confirm these preliminary data.

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.

Preliminary Results of Full Body Iron Overload Measurement by a Magnetic Susceptometer.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3714-3714
Author(s):  
Mauro Marinelli ◽  
Barbara Gianesin ◽  
Antonella Lavagetto ◽  
Martina Lamagna ◽  
Eraldo Oliveri ◽  
...  
Keyword(s):  
Iron Overload ◽  
Correlation Coefficient ◽  
Room Temperature ◽  
Hereditary Hemochromatosis ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Severe Anemia ◽  
Liver Iron ◽  
Non Invasive ◽  
Full Body

Abstract Accurate assessment of body-iron accumulation is essential for managing therapy of iron-chelating diseases characterized by iron overload such as thalassemia, hereditary hemochromatosis, myelodysplasia and other forms of severe anemia. At present, the gold standard to determine liver-iron concentration (LIC) is liver needle biopsy. In this work, we present an alternative non-invasive technique to measure LIC based on a room-temperature susceptometer. SQUID biosusceptometers and MRI are currently the only validated non-invasive methods for LIC measurements. However, SQUIDs are liquid helium-cooled superconducting devices, therefore costly and resource intensive. Furthermore, SQUIDs are only sensitive to a fraction of the liver volume because of their magnetic configuration. MRI requires large magnets with dedicated software and hardware, trained operators, and is accurate only at low iron concentration. The susceptometer presented herein measures iron overload in the whole liver, as the entire human torso fits within its region of sensitivity. Since all of its components operate at room temperature, this susceptometer is more affordable then competing techniques and can reach a wider hospital base. The study was approved by the local Ethics Committee and all subjects gave informed consent. Since February 2005, 40 patients (30 thalassemia major or intermedia, 5 hereditary hemochromatosis, 5 other severe anemia) and 68 healthy volunteers have been measured. The signal picked up by the susceptometer has two sources: an overall magnetic background of the torso and an eventual contribution from liver iron excess. After measuring the magnetic signature of a patient, statistical analysis methods and neural-network simulations (trained using the control data) are employed to estimate the background signal, given the patient anthropometric data. Liver-iron overload is then determined by subtraction of the estimated background from the total measured signal. The refinement of the methodology is in progress and, at present, the error in liver iron is about 1g (SD), corresponding to typical concentrations of 0.5 mg/cm^3. A correlation study between iron overload and blood serum-ferritin concentration in the patient population attained a correlation coefficient R~0.73. Comparison with measurements of LIC via SQUID susceptometry on a subset of 30 patients participating in the present study (carried out by Dr. A. Piga at Ospedale S. Anna, Torino, Italy) yields a correlation coefficient R~0.77. Four patients (3 thalassemia major, 1 hereditary hemochromatosis) under intensive iron depletive therapy have been measured at least twice; our estimate of liver iron reduction is compatible with the clinical data (R~0.76). Comparison with LIC measured via biopsy is in progress. All comparison were blinded. These preliminary results indicate that possible applications of this non-invasive, full-body susceptometer include monitoring the efficacy of the therapy as well as improving the diagnosis and care management of patients with iron overload. Figure Figure

Quantitative T2*MRI for Bone Marrow Iron Overload Assessment in Thalassemia Major and Intemedia Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4042-4042
Author(s):  
Antonella Meloni ◽  
Roberta Renni ◽  
Nicola Romano ◽  
Carla Cirotto ◽  
Francesco Gagliardotto ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Conflicts Of Interest ◽  
Iron Concentration ◽  
Lumbar Vertebra ◽  
Thalassemia Major ◽  
Liver Iron ◽  
Transfusion Requirements ◽  
T2 Mri

Abstract Introduction. Multiecho T2* MRI is a well-established technique for cardiac and hepatic iron overload assessment, but there are limited data on its potential to quantify iron in other organs. The aims of this study were to describe for the first time the T2* values of the bone marrow in patients with thalassemia major (TM) and intermedia (TI) and to investigate the correlation between bone marrow T2* and iron deposition in myocardium and liver. Methods. 283 TM patients (32.25±8.28 years, 144 females) and 46 TI patients (38.30±8.73 years, 17 females) enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network underwent MRI. For the measurement of iron overload, multiecho T2* sequences were used. Bone marrow T2* values were obtained on a circular regions of interest (ROI) located in the visible body of the first or second lumbar vertebra. The left ventricle was segmented into a 16-segments standardized model and the T2* value on each segment was calculated as well as the global value. In the liver the T2* value was assessed in a single ROI defined in a homogeneous area of the parenchyma]and it was converted into liver iron concentration (LIC). Results. Bone marrow T2* values were significantly lower in TM than in TI patients (7.65±6.29 vs 13.22±6.01 ms; P<0.0001). Bone marrow T2* values were significantly lower in females than in males in both the diseases (Figure 1), but they increased with age in a significant manner only in TM (R=0.343, P<0.0001). In TM bone marrow T2* values were weakly associated with global heart T2* values (R=0.143; P=0.016) and negatively correlated with LIC values (R=-0.439; P<0.0001) and mean serum ferritin levels (R=-0.582; P<0.0001). In TI no association was present between bone marrow and global heart T2* value, but bone marrow T2* values were negatively correlated with LIC values (R=-0.273; P=0.046) and mean serum ferritin levels (R=-0.569; P<0.0001). One hundred and sixty-six TM patients (58.7%) were splenectomised and splenectomised TM patients showed significant higher bone marrow T2* values than non-splenectomised patients (9.78±6.78 ms vs 4.61±3.85 ms, P<0.0001). The difference remained significant also correcting for the age, significantly higher in splenectomised patients. Fourty TI patients (87.0%) were splenectomised and bone marrow T2* were comparable between splenectomised and non-splenectomised TI patients (13.46±6.26 ms vs 11.61±4.05 ms, P=0.493). Conclusions. In both TM and TI groups, males showed significantly higher T2* values. This difference may be due to the fact that the male sex is associated with severely low bone mass , which can influence the T2* values. Bone marrow T2* values were associated with heart T2* values only in TM, maybe because in TI cardiac iron overload was not common. In both TM and TI a positive correlation was found between hepatic and bone marrow siderosis. Splenectomised TM patients showed higher bone marrow T2* values, probably due to the fact that splenectomy is generally performed in patients with hypersplenism to reduce transfusion requirements. Conversely, bone marrow T2* values were comparable in splenectomised and non-splenectomised TI patients. In fact, the current indications for splenectomy in TI include growth retardation, leukopenia, thrombocytopenia, increased transfusion demand, symptomatic splenomegaly. Moreover the transfusion iron intake is significantly lower in TI. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Cytokeratin 18 as a non invasive marker in diagnosis of NASH and its usefulness in correlation with disease severity in Egyptian patients

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
M Maher ◽  
H Abdelaziz ◽  
T yossif ◽  
M Ossama
Keyword(s):  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Disease Severity ◽  
P Value ◽  
Cytokeratin 18 ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Group I ◽  
Egyptian Patients ◽  
Group Ii

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is one of the types of fatty liver which occurs when exceeive fat is deposited in the liver due to causes other than excessive alcohol use, NAFLD is subdivided into non alcoholic fatty liver (NAFLD) and nonalcoholic steatohepatitis (NASH). In NAFLD, hepatic steatosis is present without evidence of significant inflammation, whereas in NASH, hepatic steatosis is associated with hepatic inflammation Aims To evaluate the role of CK-18 as a non invasive marker in diagnosis of NASH and its usefulness in correlation with disease severity in Egyptian patients. Patients and Methods 60 subjects were divided into 2 groups: group I: including 30 patients with NAFLD, group II: including 30 matched healthy controls Diagnosis of NASH and its discrimination from NAFL was done by fibroscan. CK-18 level in plasma was measured for all subjects using ELISA. Results CK-18 was significantly elevated in patients of group I in comparison to group II, with mean ± SD: 460 ± 279, 167 ± 56 and 149 ± 57, respectively, and P value: 0.001. with mean ±SD: 59.6± 28, when compared with control group (with 23±8) P value &lt; 0.001. ROC curve between Cases and Control regard CK18 with Area Under the Curve (AUC): 0.925. Cutoff &gt; 30 ug/l With Sensitivity: 86.67% & Specificity: 83.33%. Ck-18 was found to correlate with steatosis and fibrosis assessed by fibroscan with P value&lt; 0.001. Conclusion Measurement of serum cytokeratin 18 fragment levels (CK18) correlate with the Fibroscan (Transient Elastograph) as a non invasive tests in diagnosis & prognosis of non alcoholic fatty liver diseases (NAFLD).

Consequences and management of iron overload in sickle cell disease

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 447-456 ◽  
Author(s):  
John Porter ◽  
Maciej Garbowski
Keyword(s):  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Iron Overload ◽  
Sickle Cell ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Iron Loading ◽  
Cell Disease ◽  
Liver Iron Concentration ◽  
Liver Iron

Abstract The aims of this review are to highlight the mechanisms and consequences of iron distribution that are most relevant to transfused sickle cell disease (SCD) patients and to address the particular challenges in the monitoring and treatment of iron overload. In contrast to many inherited anemias, in SCD, iron overload does not occur without blood transfusion. The rate of iron loading in SCD depends on the blood transfusion regime: with simple hypertransfusion regimes, rates approximate to thalassemia major, but iron loading can be minimal with automated erythrocyte apheresis. The consequences of transfusional iron overload largely reflect the distribution of storage iron. In SCD, a lower proportion of transfused iron distributes extrahepatically and occurs later than in thalassemia major, so complications of iron overload to the heart and endocrine system are less common. We discuss the mechanisms by which these differences may be mediated. Treatment with iron chelation and monitoring of transfusional iron overload in SCD aim principally at controlling liver iron, thereby reducing the risk of cirrhosis and hepatocellular carcinoma. Monitoring of liver iron concentration pretreatment and in response to chelation can be estimated using serum ferritin, but noninvasive measurement of liver iron concentration using validated and widely available MRI techniques reduces the risk of under- or overtreatment. The optimal use of chelation regimes to achieve these goals is described.

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.

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