Liver disease in patients with transfusion-dependentβ-thalassemia:The emerging role of metabolism dysfunction-associated steatotic liver disease

In this Editorial,we highlight the possible role that metabolism dysfunction-associated steatotic liver disease(MASLD)may play in the future,regarding liver disease in patients with transfusion-dependent β-thalassemia(TDBT).MASLD is characterized by excessive accumulation of fat in the liver(hepatic steatosis),in the presence of cardiometabolic factors.There is a strong correlation between the occurrence of MASLD and insulin resistance,while its increased prevalence parallels the global epidemic of diabetes mellitus(DM)and obesity.Patients with TDBT need regular transfusions for life to ensure their survival.Through these transfusions,a large amount of iron is accumulated,which causes saturation of transferrin and leads to the circulation of free iron molecules,which cause damage to vital organs(primarily the liver and myocardium).Over the past,the main mechanisms for the development of liver disease in these patients have been the toxic effect of iron on the liver and chronic hepatitis C,for which modern and effective treatments have been found,resulting in successful treatment.Additional advances in the treatment and monitoring of these patients have led to a reduction in deaths,and an increase in their life expectancy.This increased survival makes them vulnerable to the onset of diseases,which until recently were mainly related to the non-thalassemic general population,such as obesity and DM.There is insufficient data in the literature regarding the prevalence of MASLD in this population or on the risk factors for its occurrence.However,it was recently shown by a study of 45 heavily transfused patients with beta-thalassemia(Padeniya et al,BJH),that the presence of steatosis is a factor influencing the value of liver elastography and thus liver fibrosis.These findings suggest that future research in the field of liver disease in patients with TDBT should be focused on the occurrence,the risk factors,and the effect of MASLD on these patients.

Comparative Study of Neurosurgical Complications of Thalassemia and Sickle Cell Disease

Introduction: Sickle cell disease and thalassemia are the most frequent hemoglobinopathies. During their evolution, they present certain complications, among which are two neurosurgical emergencies, namely spontaneous cranial epidural hematoma and non traumatic radiculo-medullary compression, with some particularities for each. Method: In order to highlight these particularities, we compared the characteristics of these two complications, from a number of publications reported between 2000 and 2021. Results: Sickle cell disease was complicated by spontaneous cranial epidural hematoma. Forty-two cases were reported, the mean age was 14.7 years (2 - 21 years) and the sex ratio was 6.4. The clinical presentation combined, in a non-traumatic context, signs of intracranial hypertension with those of neurological focalization. Neuroimaging showed epidural-type collection, often frontal and parietal in location. The incriminating mechanisms were ischemia, hemorrhage and extra medullary hematopoiesis. The treatment was surgical. Non traumatic radiculo-medullary was the complication of thalassemia. Of the 77 cases reported, the mean age was 27.5 years (9 - 66 years) and the sex ratio was 4.1. The lesions were epidural with a clear thoracic predominance and resulted from extra marrow hematopoiesis. Treatment included: hypertransfusion, radiotherapy, hydroxyurea and surgery. Vital and functional prognosis were globally satisfactory when the management was rapid. Conclusion: Cranial and spinal epidural lesions, respective complications of sickle cell disease and thalassemia, result from similar mechanisms. Their prognosis depends on the rapidity of management. .

Genetic diversity of HCV among various high risk populations(IDAs,thalassemia,hemophilia,HD patients) in Iran

Objective:To determine the patterns of distribution of HCV genotypes among high risk population in north of Iran.Methods:A cross-sectional study was conducted on 135 HCV RNA-positive high risk individuals including thalassemia,hemophilia,patients under hemodialysis and intravenous drug addicts.HCV genotypes were determined based on amplification with type-specific primers methods.Results:Among the 187 anti-HCV positive samples,only 135 (72.2%)gave HCV-RNA positvity.Over all,the most identified HCV type was genotype 3a(51.1%) followed by 1a(27.4%),1b(8.2%).Sixteen(11.9%)out of 135 HCV RNA-positive participants have infected with more than one genotype or subtypes as follow:1a/1b in 11(8.2%),2/3a in 3 (2.2%),and 1a/1b/3a in 2(1.5%).Stratification of participants revealed that HCV subtype 3a was more prominent in thalassemia,hemophilia and HD patients but 1a and 1b were frequent in intravenous drug addicts.Conclusions:This study is the first report on HCV genotypes among Iranian subjects with different exposure categories resided in Mazandaran.where genotype 3a was found to be the most frequent genotype in thalassemia,hemophilia,and hemodialysis patients but not in IDAs.Since the addiction age is decreasing in Iran and a lot of addicts are IDAs.it might change the subtype pattern of HCV in general population.

Effectiveness of Using Mean Corpuscular Volume and Mean Corpuscular Hemoglobin for Beta-thalassemia Carrier Screening in the Guangdong Population of China

Beta(β)-thalassemia is one of the most common hemoglobinopathies worldwide,creating major public health problems and social burdens in many regions.Screening forβ-thalassemia carriers is crucial for controlling this condition.To investigate the?effectiveness?of?mean?corpuscular?volume?(MCV)and mean corpuscular hemoglobin(MCH)for screeningβ-thalassemia,retrospective data were analyzed for 6,779β-thalassemia carriers subjected to genetic testing following thalassemia screening in Guangdong province between January 2018 and December 2019.

Can a polymorphism in the thalassemia gene and a heterozygote CFTR mutation cause acute pancreatitis?

The case of a 32-year-old black woman of African descent who suffered from repeated episodes of acute pancreatitis, initially triggered when flying on airplanes, is reported. She did not drink alcohol or smoke. Genetic analysis was negative for cationic trypsinogen, serine protease inhibitor Kazal type 1 and chymotrypsin C. However, hemoglobin F was elevated. Sequencing of the thalassemia gene revealed a novel alteration in the 5' region indicative of a functional abnormality of the molecule. Sequencing the cystic fibrosis transmembrane conductance regulator(CFTR) gene revealed a heterozygote sequence variant. The combination of a hemoglobin gene mutation known for thalassemia in conjunction with the hitherto undescribed CFTR mutation is suggested to pave the road for initial and repetitive pancreatitis attacks. This will be discussed.

Study of concentration of amniotic fluid Alpha-fetal protein in thalassemia fetus

Objective:To test the hypothesis that concentration of amniotic fluid alpha-fetal protein(AFAFP) is increased in thalassemia fetus.Methods:A total of 135 cases of amniocentesis admitted from July 2013 to December 2014 were included in this study.Among them 98 cases of normal fetuses were assigned into control group and 37 cases of thalassemia fetus were included as thalassemia fetus group.Alpha-fetoprotein levels detected by enzyme linked immunosorbent assay and the alpha-fetoprotein concentration were compared between the two groups.There is no significant difference in gestrational age between the two groups.Results:1.AFP concentration in thalassemia fetus group was significantly higher than that of normal control group [(1541.65±734.78) μg/mL vs.(2728.84± 1539.97) μg/mL ],and amniotic fluid AFP concentration was related to fetal thalassemia.2.AFAFP concentration in pureα-thalassemia fetus was higher than that of β thalassemia fetus or mixed αand was not significant.Conclusions:Concentration of a β thalassemia fetus,but the difference mniotic fluid alpha-fetal protein is increased in thalassemia fetus.AFP concentration inα-thalassemia fetus was higher than that of β thalassemia or mixed αand lore β thalassemia fetus but difference was not significance.Further studies are needed to exp the possible correlation between Down syndrome and biochemical markers of Thalassemia.

Spectrum of thalassemia mutations in fetuses of Han and Li ethinicities in Hainan province, China

Objective: To analyze the frequency and spectrum of thalassemia mutations in amniotic fluid samples collected from Han and Li people in Hainan province of China.Methods: We carried out a retrospective analysis on prenatal diagnosis of amniotic fluid samples collected from pregnant women who may have next generation with high risks of medium or severe thalassemia between 2005 and 2016. Diverse fetal thalassemia genotypes and mutated alleles in Han and Li people were analyzed and cmpared. Results: We examined 536 amniotic fluid samples from Han people and 588 from Li people, among which 406 Han and 500 Li samples were found to carry at least one thalassemia gene mutation, with a detection rate of 75.75% and 85.03%, respectively. Among all α-and β-thalassemia mutant alleles detected, the most frequently found mutations in Han and Li samples were SEA-type of α-thalassemia and 41/42(–CTTT) of β-thalassemia, respectively. A total of 75 severe thalassemia cases were identified in Han samples and 53 in Li samples. In most of these severe cases, parents chose to terminate pregnancy after being informed of thalassemia-related risks. Conclusions: The thalassemia mutations shows ethnic and area specificity, and that prenatal diagnosis for high-risk thalassemia carrier pregnant women is an efficient approach to prevent and control the occurrence of severe thalassemia in the high-prevalence areas.

Hepatocellular carcinoma in thalassemia:A critical review

Due to blood transfusions,thalassemics are often infected with either hepatitis C virus(HCV)or hepatitis B virus and often have hemochromatosis.Hepatocellular carcinoma(HCC)has emerged in thalassemics only recently as a result of the improvement in thalassemia outcomes.In fact,a prospective study estimated an HCC incidence inβ-thalassemia of about 2%.Although data are scanty,HCC screening in thalassemics with risk factors for HCC should be carried out.HCV treatments have some efficacy in HCV infected thalassemics despite partial contraindication to ribavirin and iron overload.However,there are no data on how HCV treatment translates into HCC prevention.Preliminary data suggest that HCC treatment in thalassemics should generally have the same outcomes as in nonthalassemics.Although coexistence of severe comorbidities makes liver transplantation challenging,this therapeutic possibility should not be precluded for well selected HCCβ-thalassemia patients.In fact,2 transfusion dependent adult HCCβ-thalassemia patients have recently undergone successful liver transplantation with a good outcome.In conclusion,HCC seems to be a developing issue in thalassemia and HCC screening should be carried out.HCC treatment,including liver transplantation,can be performed in selected patients. A multidisciplinary effort is needed for management.

Ocular findings in children with thalassemia major in Eastern Mediterranean

AIM: To investigate ophthalmologic findings in children with thalassemia major(TM) and compare the findings with healthy controls. ·METHODS: In a cross-sectional study,43 children with thalassemia major from pediatric hematology outpatient clinics from two university hospitals and age/sex matched 47 healthy children were included in the study. After a complete ophthalmic examination,tear function tests including the Schirmer test,fluorescein tear breakup time(BUT),ultrasound pachymetry,and axial length measurement were performed. Obtained data was recorded for statistical analysis and the values of right eyes were compared between groups. ·RESULTS: The mean best corrected visual acuity was 1.34 ±0.75 in TM and 1.08 ±0.28 in controls. It was found lower than 0.1 logMAR unit in 10(23.2%) children with TM and 2(4.2%) in controls,and the difference was statistically significant(P 【0.05). The mean central corneal thickness was 540±26.95 in children with TM and 536.98± 20.45μm in controls(P 】0.05). The mean axial length was 22.53±0.50 in TM and 22.57±0.43mm in the control group. The mean Schirmer test score was 19.94±6.91 in TM and 24.22±3.95mm in the control group(P 【0.01). The mean BUT score was 9.62 ±1.28 in TM and 9.73 ±0.6s in the control group(P 】0.05). ·CONCLUSION: In TM,while corneal thickness,axial length,and BUT are close to controls,the Schirmer scores are less than normal. The study revealed that TM may be affected by the tear function and visual acuity.

Early detection of cardiac involvement in thalassemia: From bench to bedside perspective

Myocardial siderosis is known as the major cause of death in thalassemia major(TM) patients since it can lead to iron overload cardiomyopathy.Although this condition can be prevented if timely effective intensive chelation is given to patients,the mortality rate of iron overload cardiomyopathy still remains high due to late detection of this condition.Various direct and indirect methods of iron assessment,including serum ferritin level,echocardiogram,non-transferrin-bound iron,cardiac magnetic resonance T2*,heart rate variability,and liver biopsy and myocardial biopsy,have been proposed for early detection of cardiac iron overload in TM patients.However,controversial evidence and limitations of their use in clinical practice exist.In this review article,all of these iron assessment methods that have been proposed or used to directly or indirectly determine the cardiac iron status in TM reported from both basic and clinical studies are comprehensively summarized and presented.Since there has been growing evidence in the past decades that cardiac magnetic resonance imaging as well as cardiac autonomic status known as the heart rate variability can provide early detection of cardiac involvement in TM patients,these two methods are also presented and discussed.The existing controversy regarding the assessment of cardiac involvement in thalassemia is also discussed.

Thalassemia Screening by Sentiment Analysis on Social Media Platform Twitter

Thalassemia syndrome is a genetic blood disorder induced by the reduction of normal hemoglobin production,resulting in a drop in the size of red blood cells.In severe forms,it can lead to death.This genetic disorder has posed a major burden on public health wherein patients with severe thalassemia need periodic therapy of iron chelation and blood transfusion for survival.Therefore,controlling thalassemia is extremely important and is made by promoting screening to the general population,particularly among thalassemia carriers.Today Twitter is one of the most influential social media platforms for sharing opinions and discussing different topics like people’s health conditions and major public health affairs.Exploring individuals’sentiments in these tweets helps the research centers to formulate strategies to promote thalassemia screening to the public.An effective Lexiconbased approach has been introduced in this study by highlighting a classifier called valence aware dictionary for sentiment reasoning(VADER).In this study applied twitter intelligence tool(TWINT),Natural Language Toolkit(NLTK),and VADER constitute the three main tools.VADER represents a gold-standard sentiment lexicon,which is basically tailored to attitudes that are communicated by using social media.The contribution of this study is to introduce an effective Lexicon-based approach by highlighting a classifier calledVADERto analyze the sentiment of the general population,particularly among thalassemia carriers on the social media platform Twitter.In this study,the results showed that the proposed approach achieved 0.829,0.816,and 0.818 regarding precision,recall,together with F-score,respectively.The tweets were crawled using the search keywords,“thalassemia screening,”thalassemia test,“and thalassemia diagnosis”.Finally,results showed that India and Pakistan ranked the highest in mentions in tweets by the public’s conversations on thalassemia screening with 181 and 164 tweets,respectively.

Effects of variant UDP-glucuronosyltransferase 1A1 gene, glucose-6-phosphate dehydrogenase deficiency and thalassemia on cholelithiasis

AIM： To test the hypothesis that the variant UDP- glucuronosyltransferase 1A1 （UGT1A1） gene, glucose-6- phosphate dehydrogenase （G6PD） deficiency, and thalassemia influence bilirubin metabolism and play a role in the development of cholelithiasis. METHODS： A total of 372 Taiwan Chinese with cholelithiasis who had undergone cholecystectomy and 293 healthy individuals were divided into case and control groups, respectively. PCR and restriction fragment length polymorphism were used to analyze the promoter area and nucleotides 211, 686, 1 091, and 1 456 of the UGT1A1 gene for all subjects and the gene variants for thalassemia and G6PD deficiency. RESULTS： Variation frequencies for the cholelithiasis patients were 16.1%, 25.8%, 5.4%, and 4.3% for A（TA）6 TAA/A（TA）TTAA （6/7）, heterozygosity within the coding region, compound heterozygosity, and homozygosity of the UGT1A1 gene, respectively. Comparing the case and control groups, a statistically significant difference in frequency was demonstrated for the homozygous variation of the UGT1A1 gene （P = 0.012, Z2 test）, but not for the other variations. Further, no difference was demonstrated in a between-group comparison of the incidence of G6PD deficiency and thalassemia （2.7% vs 2.4% and 5.1% vs 5.1%, respectively）. The bilirubin levels for the cholelithiasis patients with the homozygous variant-UGT1A1 gene were significantly different from the control analog （18.0±6.5 and 12.7±2.9 μmol/L, respectively; P〈0.001, Student＇s ttest）.CONCLUSION： Our results show that the homozygous variation in the UGT1A1 gene is a risk factor for the development of cholelithiasis in Taiwan Chinese. 2005 The WJG Press and Elsevier Inc. All rights reserved

Iron dysregulation in beta-thalassemia

Iron deficiency anemia and iron overload conditions affect more than one billion people worldwide.Iron homeostasis involves the regulation of cells that export iron into the plasma and cells that utilize or store iron.The cellular iron balance in humans is primarily mediated by the hepcidin-ferroportin axis.Ferroportin is the sole cellular iron export protein,and its expression is regulated transcriptionally,post-transcriptionally and posttranslationally.Hepcidin,a hormone produced by liver cells,post-translationally regulates ferroportin expression on iron exporting cells by binding with ferroportin and promoting its internalization by endocytosis and subsequent degradation by lysosomes.Dysregulation of iron homeostasis leading to iron deposition in vital organs is the main cause of death in betathalassemia patients.Beta-thalassemia patients show marked hepcidin suppression,ineffective eiythropoiesis,anemia and iron overload.Beta-thalassemia is common in the Mediterranean region,Southeast Asia and the Indian subcontinent,and the focus of this review is to provide an update on the factors mediating hepcidin related iron dysregulation in beta-thalassemia disease.Understanding this process may pave the way for new treatments to ameliorate iron overloading and improve the long term prognosis of these patients.

An ironic case of liver infections:Yersinia enterocolitis in the setting of thalassemia

A 49 years old Vietnamese male with a history of thalassemia,presented with gastrointestinal symptoms and signs of hemolysis.He was diagnosed with yersinia enterocolitis.Yersinia is a gram-negative rod that most frequently occurs in children especially during the winter months.In the current case,the bone marrow biopsy showed hemophagocytosis along with positive cultures for Yersinia.The microorganism likely triggered hemophagocytosis.This syndrome,also known as,hemophagocytic lymphohistiocytosis,is defined by fever for more than 7 d,cytopenia of two or more cell lines,hemophagocytosis,hepatitis,serum ferritin greater than500,jaundice,lymphadenopathy,and hepatosplenomegaly.This disorder can be either familial or secondary to a strong immunologic activation.Both have an overwhelming activation of T-cells and macrophages.

Partial splenic embolization in the management of thalassemia major A report of 40 cases

Forty children with thalassemia major were treated with gelfoam particles for partialsplenic embolization (PSE).The embolization of the spleen ranged from 50 to 85 per cent.Af-ter PSE,the spleen shrank greatly,and the symptoms of anemia improved.The immunologicalfunction of the body was the same as before PSE.All patients showed a marked reduction intransfusion requirements.Therefore,it is believed that PSE is an effective therapy for tha-lassemia major.

Intracranial Extramedullary Hematopoiesis in β-thalassemia Major

A case of β-thalassemia major with a huge mass of hernatopoictic tissuc firmly attached tothe dura mater was reported This is the first case reported in China.

Up-regulation of NKG2A Inhibitory Receptor on Circulating NK Cells Contributes to Transfusion-induced Immunodepression in Patients with β-thalassemia Major

Accumulating evidence has shown that allogeneic blood transfusions can induce significant immunosuppression in recipients, and thereby increase the risk of postoperative infection and/or tumor relapse. Although it is well known that natural killer（NK） cells are responsible for the immunodepression effects of transfusion, the underlying mechanisms remain obscure. In this study, we investigated the role of NK cells in transfusion-induced immunodepression in β-thalassemia major. The proportion of circulating NK cells and the expression of NK receptors（NKG2A, CD158 a, NKP30, NKP46 and NKG2D） as well as CD107 a were detected by multicolor flow cytometry. IFN-γ production by circulating NK cells was detected by intracellular cytokine staining. Our results showed that the proportion and cytotoxicity（CD107a expression） of circulating NK cells in transfusion-dependent β-thalassemia major patients were remarkably lower than those of β-thalassemia minor patients or healthy volunteers. Expression of NKG2 A inhibitory receptor on circulating NK cells in patients with β-thalassemia major was remarkably up-regulated, but there were no significant differences in the expression levels of NKP30, NKP46, NKG2 D, CD158 a and IFN-γ. These results indicate NKG2 A inhibitory receptor may play a key role in transfusion-induced immunodepression of NK cells in patients with β-thalassemia major.

Amelioration of β^(654)-thalassemia in mouse model with the knockdown of aberrantly spliced β-globin mRNA

Large amounts of aberrantly spliced mRNA from the β^654 allele was present in erythroid cells, which might impair the erythropoiesis. A therapeutic strategy for β-thalassemia was explored by knocking down the aberrantly spliced mRNA of β-globin. Lentiviral vector with siRNA fragment targets on the specific portion of β^654-globin aberrantly spliced pre-mRNA was constructed. In HeLa β^654 cells, the siRNA vector could reduce approximately 60% of aberrantly spliced mRNA, which was assessed by RT-PCR and qRT-PCR. Furthermore, a disease model of β^654 thalassemia mice with lentiviral-mediated siRNA was produced by subzonal injection （named Hβi-Hbb^th-4/Hbb^＋ transgenic mice）. Our results showed that the hemotological parameters were improved in Hβi-Hbb^th-4/Hbb^＋ transgenic mice. This study provides a potential way for β^654-thalassemia therapy by knocking down the aberrantly spliced β-globin mRNA, whilst supporting that the aberrantly spliced β-globin mRNA may aggravate the disease.

Carrier Screening and Prenatal Gene Diagnosis of β-thalassemia by PCR-RDB Technique

In order to identify the distribution of gene types of β-thalassemia and reduce the birthrates of β-thalassemia major in Guiyang area, 1054 pregnant women and their spouses from Affiliated Hospital, Guiyang Medical College were screened. The positive samples were analyzed with polymerase chain reaction and reverse dot blot method (PCR-RDB). When both partners were heterozygous identified as carriers for β- thalassemia, the risk of having a fetus who was homozygous or compound heterozygous was 2.66 %; the ratio of male to female was 1/1.15. Seven types of mutation were identified. CD17 and CD41-42 were dominant among them. Among the 4 cases subject to prenatal gene diagnosis, one fetus was completely normal and 3 fetuses were diagnosed as having β-thalassemia major (1 homozygous and 2 compound heterozygous). The fetuses diagnosed as β-thalassemia major were selectively terminated within two weeks. It was concluded that the birthrate of β-thalassemia major in Guiyang area was reduced and the target of improving birth outcome and child development has been achieved.

Epidemiological analysis on the incidence of thalassemia and G6PD deficiency in the population of childbearing age in Hengxian county in Guangxi

Objective:We investigated the incidence of thalassemia and glucose-6-phosphate dehydrogenase(G6PD)deficiency in people of childbearing age of Hengxian in Guangxi,to further provide scientific data for the diagnosis,treatment and prepotency consultation for thalassemia.Methods:A total of 12,489subjects at childbearing age who were undergoing a routine prenatal check-up in Hengxian family planning service stations were recruited in this study between January 2014and December 2014.They were screened for thalassemia by mean corpuscular volume(MCV)and mean corpuscular hemoglobin(MCH).The people with positive results then underwent thalassemia gene test.The G6PD activities were measured by enzyme kinetic method.Results:The incidence of thalassemia was 20.26%(2,530/12,489)in Hengxian,among which the incidences ofα-thalassemia,β-thalassemia,andα-thalassemia co-inheritance ofβ-thalassemia were13.20%,6.13%and 0.93%respectively.The incidence of G6PD deficiency was 5.39%(617/12,489),and the ratio between male and female is 4.27∶1.25types ofα-thalassemia genotype and 8types ofβ-thalassemia genotype were identified.The genotypes ofSEA/ααand the genotypes of41-42Mβ/Nβwere the most common genetic types forα-thalassemia andβ-thalassemia respectively.Conclusion:Hengxian is a high prevalence area of thalassemia and G6PD deficiency.SEAmutation type is the most common type inα-thalassemia,and the CD 41-42mutation is the most common type inβ-thalassemia in Hengxian.