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Background and Aims: Direct antiviral agents (DAAs) have revolutionised the standard of care for the treatment of hepatitis even in patients with hemoglobinopathies. The aim of this study is to show how, thanks to DAAs, HCV infection has been substantially eradicated in one of the biggest Centres for the management of Thalassemia in Europe., Methods: Thalassemia major patients regularly transfused and iron chelated in Cagliari (Italy) who were HCV-RNA positive were evaluated for the potential prescription of antiviral therapy., Results: A total of 99 patients, 26 of whom had been diagnosed with cirrhosis, were treated with at least one dose of DAAs, which proved to be safe and well tolerated. Two of the patients died during the treatment after becoming HCV-RNA negative while another voluntarily interrupted the therapy. The final SVR in the patients who completed the treatment was 100%, while measuring 97% (96/99) in the Intention-to-Treat analysis. After DAAs, no new cases of hepatocellular carcinoma have been reported., Conclusions: The use of DAAs in patients suffering from beta-Thalassemia major with chronic hepatitis C or cirrhosis can be considered safe and effective. Close monitoring for hepatocellular carcinoma development is, in any case, recommended indefinitely post-SVR., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The aim of the study was to assess the current state in terms of liver and heart iron overload as well as of liver and heart related morbidity and mortality in a large cohort of thalassemia patients. Myocardial iron loading was present in 28.9% patients, which was severe in 3.2%. Liver iron was normal in 9.3% and severe in 15%. The rate of cardiac deaths started to decrease between 2000 and 2003 and dropped significantly afterwards. The prescription of combination therapy soon after the hospital admission for decompensated heart failure was associated with a decrease in the short-term mortality. In 111 adult patients who underwent liver elastometry, 14 HCVRNA positive subjects and 2 HCVRNA negative, had stiffness values suggestive of cirrhosis. No cases of hepatocarcinoma were reported. Liver "iron free foci" occurred in a HCV negative patient and the occurrence of a malignant epithelioid hemangioendothelioma led to liver transplantation in another. The study suggests that a subset of patients continues to develop progressive hemosiderosis that may lead to cardiac disease and death. Beyond its key role in preventing myocardial iron overload, liver iron chelation is essential for hampering the onset of hepatic tumors, which may not be limited to hepatocarcinoma., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This study aimed to verify the impact of heart magnetic resonance imaging on chelation choices and patient compliance in a single-institution cohort as well as its predictive value for heart failure and arrhythmias. Abnormal cardiac T2* values determined changes in treatment in most subjects. Heart T2* was confirmed to be highly predictive over 1 year for heart failure and arrhythmias. The choice of chelation regimens known to remove heart iron efficiently was not sufficient by itself to influence the risk. Compliance with treatment had a more remarkable role., (© 2013 John Wiley & Sons Ltd.)

Objective: Insulin resistance (IR) increases during puberty in normal children. IR is the first adverse metabolic event of obesity, and the marker of the metabolic syndrome. We aimed to study the effect of puberty on IR in obese and normal-weight children., Design: Cross-sectional evaluation of fasting glucose, insulin concentrations, and homeostasis model assessment of IR (HOMA-IR) in obese and control children throughout puberty., Patients and Methods: We recruited 424 obese children (207 pre-pubertal and 217 pubertal divided in Tanner stages 2-3, 4, and 5) and estimated IR using the HOMA-IR index. Data were compared to those obtained in 123 healthy normal-weight children (40 pre-pubertal and 83 pubertal divided in Tanner stages 2-3, 4, and 5)., Results: In the obese children mean HOMA-IR increased progressively across Tanner stages, and was significantly higher in all groups (pre-pubertal and Tanner stages 2-3, 4, and 5) of obese than in control children. HOMA-IR was significantly correlated with BMI., Conclusions: HOMA-IR in obese children increases at puberty more than in normal-weight children and does not return to pre-pubertal values at the end of puberty.

Objectives: Evaluation of GH response to ghrelin in patients with GH deficiency (GHD) may help to elucidate the site and mechanism of action of ghrelin. We aimed to investigate the GH-releasing effect of ghrelin in children and young adults with childhood-onset GHD., Design: All subjects underwent ghrelin testing and neuro-imaging examination. Magnetic resonance imaging evidenced the presence of a vascular pituitary stalk (VPS) or its complete absence (PSA)., Patients and Methods: Seventeen prepubertal children and nine adult patients with childhood-onset GHD were selected for the study. The children were enrolled at a median age of 5.8 years. The adult subjects were included at a median age of 23.3 years. The diagnosis of GHD in the adult patients had been established at a median age of 8.5 years. Ghrelin was administered at a dose of 1 microg/kg body weight, i.v. at time zero, and blood for GH determination was obtained at 0, 15, 30, 45, 60, 75, 90, 105 and 120 min., Results: Median GH response after ghrelin was similar between children and adults. Median peak GH response to ghrelin (7.45 microg/l, IQR: 3.9-11.3 microg/l) was significantly higher in patients with VPS (10.9 microg/l, IQR: 2.4-15.1 mcirog/l) than in those with PSA (IQR: 2.3-6.7 microg/l; P=0.001). It was significantly higher in subjects with isolated GHD (12.5 microg/l, IQR: 10.8-15.5 microg/l) than in those with multiple pituitary hormone deficiencies (5.15 microg/l, IQR: 2.4-9.0 microg/l; P=0.003). No correlation was found between the GH peak after ghrelin and body mass index., Conclusion: The GH response to ghrelin in patients with congenital hypopituitarism depends on the degree of the anatomical abnormalities and lends further support to the assumption that the main action of the peptide is exerted at the hypothalamic level and requires the integrity of hypothalamic-pituitary connections.

Background and Objectives: Deferasirox (ICL670) is a novel once-daily oral iron chelator developed for the treatment of chronic iron overload from blood transfusions. This study evaluated the safety and tolerability of deferasirox in pediatric patients with transfusion-dependent beta-thalassemia major. Efficacy and pharmacokinetic assessments were secondary objectives., Design and Methods: Forty patients equally stratified into two age groups--children (2 to <12 years) and adolescents (12-17 years)--were treated with deferasirox for 48 weeks. All received once-daily deferasirox 10 mg/kg/day with modifications allowed after 12 weeks' treatment. Safety, liver iron concentration (LIC), serum ferritin and pharmacokinetics were assessed., Results: Thirty-nine patients completed the study. One withdrew due to a skin rash. Adverse events were typical of this population, but only four were considered related to the study drug: mild nausea (two adolescents) and moderate skin rash (two children). There were no serious adverse events related to the study drug. Five patients briefly interrupted treatment due to elevated transaminases with no recurrences when treatment resumed. The mean deferasirox dose was 11.3 mg/kg/day. Overall LIC increased gradually from week 12 as mean daily iron intake was higher than excretion. Steady-state plasma levels of deferasirox and its iron complex, Fe-[deferasirox]2, were comparable between children and adolescents., Interpretation and Conclusions: Deferasirox was well tolerated by this pediatric population. Toxicities known to be associated with other commercially available iron chelators were not observed. The dose employed was too low to induce a net negative iron balance in this regularly transfused population. Pharmacokinetic data support a once-daily dosing regimen based on body weight.