IFNL3 polymorphisms and HCV infection in patients with beta thalassemia.

Unlabelled: BACKGROUND AND RATIONALE FOR THE STUDY: Genome-wide association studies have identified host genetic variation to be critical for spontaneous clearance and treatment response in patients infected with hepatitis C virus. Recently, the role of the IFNL3 polymorphisms in influencing the spontaneous clearance of HCV, the response to interferon and the progression of liver fibrosis, was also demonstrated in patients with thalassemia major infected by genotype 1b. In the present study we retrospectively analyzed 368 anti-HCV positive patients with beta-thalassemia at two Italian major centers in Cagliari and Torino.

A genetic score for the prediction of beta-thalassemia severity.

Clinical and hematologic characteristics of beta(β)-thalassemia are determined by several factors resulting in a wide spectrum of severity. Phenotype modulators are: HBB mutations, HBA defects and fetal hemoglobin production modulators (HBG2:g.-158C>T polymorphism, HBS1L-MYB intergenic region and the BCL11A).

Hepatocellular carcinoma in thalassaemia: an update of the Italian Registry.

The risk of developing hepatocellular carcinoma (HCC) in patients with thalassaemia is increased by transfusion-transmitted infections and haemosiderosis. All Italian Thalassaemia Centres use an ad hoc form to report all diagnoses of HCC to the Italian Registry. Since our last report, in 2002, up to December 2012, 62 new cases were identified, 52% of whom were affected by thalassaemia major (TM) and 45% by thalassaemia intermedia (TI).

Prevalence and risk factors for pulmonary arterial hypertension in a large group of β-thalassemia patients using right heart catheterization: a Webthal study.

Background: Pulmonary arterial hypertension (PAH) remains a concern in patients with β-thalassemia major (TM) and intermedia (TI); however, studies evaluating its prevalence and risk factors using systematic confirmation on right heart catheterization are lacking.

Methods And Results: This was a multicenter cross-sectional study of 1309 Italian β-thalassemia patients (mean age 36.4±9.

Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis.

Chronic hepatitis C may follow a mild and stable disease course or progress rapidly to cirrhosis and liver-related death. The mechanisms underlying the different rates of disease progression are unknown. Using serial, prospectively collected samples from cases of transfusion-associated hepatitis C, we identified outcome-specific features that predict long-term disease severity.

Renal function in patients with β-thalassaemia major: a long-term follow-up study.

Background: Little information is available about the kidney's involvement in patients with β-thalassaemia major (TM). In particular, there are no studies reporting the outcome of renal function over time.

Methods: In this retrospective study, we evaluated the changes in estimated glomerular filtration rate (eGFR) in 81 adult patients with TM followed for 10 years.

Association of chronic hepatitis C with recurrent brief depression.

Background: Depressive syndromes, including recurrent brief depression (RBD), have frequently been observed in association with chronic diseases characterized by immune activation, such as autoimmune thyroiditis or celiac disease. However, the association of RBD with chronic hepatitis C (CHC), a disease with an increased incidence of major depressive disorders, is unknown.

Cases: 135 (83 males, 52 females) consecutive treatment-naïve patients with CHC.

Genetic modifiers of β-thalassemia and clinical severity as assessed by age at first transfusion.

Background: The clinical and hematologic features of β-thalassemia are modulated by different factors, resulting in a wide range of clinical severity. The main factors are the type of disease-causing mutation and the ability to produce α-globin and γ-globin chains. In the present study we investigated the respective contributions of known modifiers to the prediction of the clinical severity of β-thalassemia as assessed by the patients' age at first transfusion.

Feasibility, reproducibility, and reliability for the T*2 iron evaluation at 3 T in comparison with 1.5 T.

This study aimed to determine the feasibility, reproducibility, and reliability of the multiecho T*(2) Magnetic resonance imaging technique at 3 T for myocardial and liver iron burden quantification and the relationship between T*(2) values at 3 and 1.5 T. Thirty-eight transfusion-dependent patients and 20 healthy subjects were studied.

Case report: thalassemia intermedia patient with hypertension non-responsive to combined medical treatment.

Pheochromocytoma is a rare disease in the general population and, to the best of our knowledge, only one case has been reported so far in patients with hemoglobinopathies. We describe the occurrence of pheochromocytoma in a patient with thalassemia intermedia associated with Gilbert's disease and Crigler- Najjar Type 2 syndrome.

β-thalassemia and thyroid failure: is there a role for thyroid autoimmunity?

Autoimmunity is not believed to be involved in tissue damage of Β-Thalassemia (Β-Thal), although nonspecific triggering of autoimmunity by iron overload has been suggested. We recently re-evaluated thyroid function and autoimmunity in 132 Β-Thal patients born and living in Sardinia Island, where a high prevalence of both Β-Thal and autoimmune disease is well documented and in 1002 age and sex-matched euthyroid individuals from the general population. The prevalence of primary hypothyroidism in Β-Thal patients was 28.

Evidence for a proatherogenic biochemical phenotype in beta thalassemia minor and intermedia.

The purpose of this study was to focus on pathophysiological mechanisms linking β-thalassemia intermedia (β-TI) and minor (β-TMI) with cardiovascular risk. Iron status, prooxidant-antioxidant balance and lipid profiles in serum, and lipid content in peripheral blood mononuclear cells (PBMCs) were evaluated in 20 β-TMI subjects, 22 β-TI patients and in 30 nonthalassemic blood donors. The mRNA levels of some genes involved in the regulation of iron and cholesterol metabolism were also determined.

Thalassemia intermedia is associated with a proatherogenic biochemical phenotype.

Objective: Unlike beta thalassemia major (β-TM) in which cardiac siderosis represents the leading cause of mortality and morbidity, in beta thalassemia intermedia (β-TI), pulmonary hypertension (PHT) and thrombosis seems to be the major cardiovascular complications. However, the mechanism underlying these complications in β-TI is still unclear. Endothelial dysfunction, the key early event in atherogenesis, is now emerging as an important cardiovascular risk determiner in β-TI patients.

Increased survival and reversion of iron-induced cardiac disease in patients with thalassemia major receiving intensive combined chelation therapy as compared to desferoxamine alone.

Myocardial iron overload is the leading cause of death in patients with beta-thalassemia major. An intensification monotherapy with deferoxamine (DFO) as well as a combination therapy with DFO and deferiprone (DFP) reduces myocardial iron and improves cardiac function. However, the prognosis for thalassemia major patients with established cardiac disease switched from DFO monotherapy to combined DFP/DFO chelation is unknown.

Amelioration of Sardinian beta0 thalassemia by genetic modifiers.

Sardinian beta-thalassemia patients all are homozygotes for the same null allele in the beta-globin gene, but the clinical manifestations are extremely variable in severity. Previous studies have shown that the coinheritance of alpha-thalassemia or the presence of genetic variants that sustain fetal hemoglobin production has a strong impact on ameliorating the clinical phenotype. Here we evaluate the contribution of variants in the BCL11A, and HBS1L-MYB genes, implicated in the regulation of fetal hemoglobin, and of alpha-thalassemia coinheritance in 50 thalassemia intermedia and 75 thalassemia major patients.

Anemia in beta-thalassemia patients targets hepatic hepcidin transcript levels independently of iron metabolism genes controlling hepcidin expression.

Thalassemia associates anemia and iron overload, two opposite stimuli regulating hepcidin gene expression. We characterized hepatic hepcidin expression in 10 thalassemia major and 13 thalassemia intermedia patients. Hepcidin mRNA levels were decreased in the thalassemia intermedia group which presented both lower hemoglobin and higher plasma soluble transferrin receptor levels.

Association of chronic hepatitis C with major depressive disorders: irrespective of interferon-alpha therapy.

Background: Mood and anxiety symptoms in chronic hepatitis C (CHC) may be related to the patient awareness of the diagnosis and prognosis, to side effects induced by interferon (IFN)-alpha treatment, as well as to substance abuse. However, the observation of metabolic alterations in patients with CHC has led to hypothesize a direct effect of hepatitis C virus (HCV) on brain function. This study was aimed at elucidating whether CHC is associated with specific anxiety or mood disorders independently of confounding factors.

Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with beta-thalassemia.

Background: Iron chelation therapy (ICT) with deferoxamine (DFO), the current standard for the treatment of iron overload in patients with transfusion-dependent disorders such as beta-thalassemia, requires regular subcutaneous or intravenous infusions. This can lead to reduced quality of life and poor adherence, resulting in increased morbidity and mortality in iron-overloaded patients with beta-thalassemia. Deferasirox is an orally administered iron chelator that has been approved for use in the United States, Switzerland, and other countries.

Standardized T2* map of normal human heart in vivo to correct T2* segmental artefacts.

A segmental, multislice, multi-echo T2* MRI approach could be useful in heart iron-overloaded patients to account for heterogeneous iron distribution, demonstrated by histological studies. However, segmental T2* assessment in heart can be affected by the presence of geometrical and susceptibility artefacts, which can act on different segments in different ways. The aim of this study was to assess T2* value distribution in the left ventricle and to develop a correction procedure to compensate for artefactual variations in segmental analysis.

Severe autoimmune hemolytic anemia in a patient with chronic hepatitis C during treatment with peginterferon alfa-2a and ribavirin.

Peginterferon (Peg-IFN) alfa in combination with ribavirin represents the gold standard treatment for chronic hepatitis C, but is associated with various side effects, especially hematological abnormalities. We report here a case of severe autoimmune hemolytic anemia (AIHA) complicated by symptomatic myocardial ischemia in a patient with chronic hepatitis C during combination therapy. The worsening hemolysis after ribavirin withdrawal and exclusion of other causes implicated Peg-IFN alfa as the cause of AIHA.

Long-term benefit of interferon alpha therapy of chronic hepatitis D: regression of advanced hepatic fibrosis.

Background & Aims: Little is known about the long-term effects of interferon alpha on clinical outcome and survival of patients with chronic hepatitis D.

Methods: Thirty-six patients with chronic hepatitis D who participated in a randomized controlled trial of a 48-week course of high (9 million units) or low (3 million units) doses of interferon alpha or no treatment were followed for an additional 2 to 14 years.

Results: Long-term survival was significantly longer in the high-dose group than in untreated controls (P = 0.

Hepatocellular carcinoma in the thalassaemia syndromes.

Hepatocellular carcinoma (HCC) frequently complicates hepatic cirrhosis secondary to viral infection or iron overload. Therefore, patients affected by thalassaemia syndromes have a theoretically high risk of developing the tumour. We collected data on patients attending Italian centres for the treatment of thalassaemia.

Fetal HLA typing in beta thalassaemia: implications for haemopoietic stem-cell transplantation.

Stem-cell transplantation can cure beta thalassaemia. We aimed to assess whether fetal HLA typing done early in the pregnancy of couples who were at risk of beta thalassaemia could provide an alternative to pregnancy termination if the prospect of a bone-marrow transplantation from a family member was available. In our clinic in Sardinia, we did fetal HLA typing for 49 couples at risk of having a baby with beta thalassaemia.