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.

scholarly journals Hemostatic abnormalities in children with thalassemia major and liver iron overload

2018 ◽  
Vol 58 (4) ◽  
pp. 175-9
Author(s):  
Pustika Amalia Wahidiyat ◽  
Stephen Diah Iskandar ◽  
Novie Amelia Chozie ◽  
Damayanti Sekarsari
Keyword(s):  
Iron Overload ◽  
Prothrombin Time ◽  
Thalassemia Major ◽  
Cross Sectional Study ◽  
Iron Deposition ◽  
Severe Liver ◽  
Liver Iron ◽  
Cross Sectional ◽  
Prolonged Aptt ◽  
Liver Iron Overload

Background Thalassemia major (TM) patients are susceptible to liver dysfunction due to iron deposition. Pediatric TM patients often present with bleeding. Blood loss necessitates transfusions, leading to increased iron absorption from the gut. Objective To study hemostatic abnormalities in children with TM and iron deposition in the liver. Methods This cross-sectional study involved 190 non-splenectomized children with TM. Liver iron deposition was evaluated using T2* MRI. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet counts were assessed from blood specimens. Results Most subjects were diagnosed with β-thalassemia and β-thalassemia/HbE. The majority of subjects were on deferiprone (DFP) treatment. Approximately 89.5% of subjects had liver iron overload. Prolongation of PT and aPTT, as well as thrombocytopenia were observed in 60%, 27.9%, and 19.5% of subjects, respectively. Prolonged aPTT and thrombocytopenia were observed three times more frequently in subjects with moderate - severe liver iron overload than in subjects with normal - mild liver iron overload (P=0.04 and 0.001, respectively). Conclusion Most TM subjects have liver iron overload ranging from mild to severe. Prothrombin time and prolongation, as well as aPTT prolongation, and thrombocytopenia are easily found in TM children. There were significantly more moderate - severe liver iron deposition patients with aPTT prolongation and thrombocytopenia than normal – mild patients with these conditions. Hence, we suggest that pediatric TM patients undergo liver iron deposition evaluations and use iron chelators in an optimal manner, in order to limit the risk of bleeding.

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.

Low Activity of Cytochrome P450 1A2 (CYP1A2) Enzyme May Protect From Iron Accumulation in Children and Adults with Transfusion Depended β-Thalassemia Major

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2153-2153
Author(s):  
Shoshana Revel-Vilk ◽  
Itamar Nitzan ◽  
Ada Goldfarb ◽  
Nilla Hemed ◽  
Eyal Shteyer
Keyword(s):  
Blood Transfusion ◽  
Normal Liver ◽  
Thalassemia Major ◽  
Iron Accumulation ◽  
Liver Mri ◽  
Cytochrome P450 1A2 ◽  
Origin Time ◽  
Liver Iron ◽  
Low Activity ◽  
T2 Mri

Abstract Abstract 2153 In human, normal iron homeostasis fails to prevent the harmful accumulation of iron in patients who require regular blood transfusions. Some patients will progress to liver fibrosis and cirrhosis, but others, with the same degree of iron overload, would not express any liver damage. Cytochrome P450 1A2 (CYP1A2), a cytochrome enzyme with pivotal role in hepatic drug metabolism, was shown in a CYP1A2−/− mice to be essential for hepatic iron toxicity. The aim of this study was to assess the activity of CYP1A2 in relation to iron load in children and adults with transfusion-depended β-thalassemia major (TM) using the 13C-methacetin breath test. Methods: 13 C-methacetin continuous online breath test (MBT, BreathID® Exalenz Bioscience) was performed in children and adults with transfusion-depended TM. MBT parameters including PDR peak (percent dose recovered per hour), cumulative percentage of 13C recovery at 20 minutes (CPDR20) after ingestion of methacetin and time to peak PDR (TTP) were correlated with various clinical, blood and MRI measures. The t-test was used to assess difference of normally distributed continuous data, Mann-Whitney test was used to assess difference of non-normally distributed continuous data and the Fisher's exact test was used to assess differences of categorical data. The study was approved by the Institutional Review Board. Results: Thirty patients [Jewish Kurdistan origin (n=14), Arab origin (n=16)] were enrolled to the study. The median (range) age of participants was 30 (1–60) years. All patients were treated with regular blood transfusion and all but one patient, were treated with iron chelation therapy [Deferoxamine (n =4), Deferiprone (n=2), Deferasirox (n=15), Combinations (n=7)]. Time from starting regular transfusion ranged from 0.8–56 years. Mean red blood cell (RBC) transfused was 100 cc/kg/year. Plasma ferritin level < 1000 mcg/l was found in 14 patients, and was not associated with age, origin, time of initiation of regular blood transfusion and amount of RBC transfusion. The PDR peak and CPDR20 were significantly lower in patients with ferritin levels < 1000 mcg/l compared to those with ferritin levels > 1000 mcg/l (PDR peak, mean±SD: 24±8 vs. 31± 10, p=0.013; CPDR20: 3.9± 2 vs. 5.5± 2.2, p=0.045, t-test). During the study period, 21 patients had T2* MRI scans. Liver MRI was normal (T2* MRI > 6.3 milliseconds) in 8 patients, and was not associated with age, origin, time of initiation of regular blood transfusion and amount of RBC transfusion. As expected, plasma ferritin levels were significantly lower in patients with normal liver MRI (Ferritin, median (range): 376 (110–1506) vs.1349 (205–8223), p=0.008, Mann-Whitney test). Decreased activity of CYP1A2 (PDR peak < 20%/hour) was associated with normal liver MRI (Table 1). All patients with decreased activity of CYP1A2 and normal liver MRI were from Jewish Kurdistan origin. Conclusions: Our study is the first to show an association between low activity of CYP1A2 and low liver iron accumulation in transfusion depended TM patients. Similar to the murine model, this finding may suggest that primary low CYP1A2 activity protects from iron accumulation. The fact that CPY1A2 activity in most patients with liver iron accumulation is normal implies that decreasing dosage of various drugs is probably not warranted in patients with hepatic iron overload. Further larger studies and genetic testing are needed to confirm our observations. Disclosures: No relevant conflicts of interest to declare.

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.

scholarly journals Correlation of Cardiac and Liver Iron Level with T2*MRI and Vitamin D3 Serum Level in Patients with Thalassemia Major

2020 ◽  
Vol Volume 11 ◽  
pp. 83-87
Author(s):  
Roya Shaykhbaygloo ◽  
Alireza Moradabadi ◽  
Hassan Taherahmadi ◽  
Mohammad Rafiei ◽  
Fariborz Lotfi ◽  
...  
Keyword(s):  
Serum Level ◽  
Vitamin D3 ◽  
Thalassemia Major ◽  
Iron Level ◽  
Liver Iron ◽  
T2 Mri

α-interferon treatment in thalassemia major patients with chronic hepatitis C and liver iron overload

1998 ◽  
Vol 28 ◽  
pp. 191
Author(s):  
MG Clemente ◽  
R Balloi ◽  
PP Muroni ◽  
C Dessì ◽  
G Cornacchia ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Iron Overload ◽  
Chronic Hepatitis C ◽  
Thalassemia Major ◽  
Interferon Treatment ◽  
Liver Iron ◽  
Liver Iron Overload

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.

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