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Progression of liver fibrosis in patients with hemoglobinopathies is strongly related to the severity of iron overload and the presence of chronic hepatitis C virus (HCV) infection. Effective iron chelation therapy and HCV infection eradication may prevent liver complications. The European Association for the Study of the Liver guidelines recommend interferon‐free regimens for the treatment of HCV infection in patients with hemoglobinopathies. However, data regarding the use of direct‐acting antiviral drugs (DAAs) in this patient population are few. This observational study evaluated the safety and efficacy of therapy with DAAs in an Italian cohort of patients with hemoglobinopathies, chronic HCV infection and advanced liver fibrosis. Between March 2015 and December 2016, 139 patients received DAAs and completed 12 weeks of follow up after the end of treatment for the evaluation of sustained virological response (12SVR). The 12SVR (93.5%) was comparable with that typically observed in cirrhotic patients without hemoglobinopathies. Three patients died during the period of observation of causes unrelated to DAAs. One patient did not achieve a virological response and five (3.6%) relapsed during 12 weeks of follow‐up after the end of therapy. In addition, patients showed significant reductions in serum ferritin at 12 weeks to levels similar to those observed in a control group of 39 patients with thalassemia major without HCV infection, who adhered to chelation therapy and had no overt iron overload. In conclusion, the use of DAAs appears to be safe and effective in patients with hemoglobinopathies and advanced liver disease due to HCV.

An accurate assessment of body iron accumulation is essential for the diagnosis and therapy of iron overload in diseases, such as hemochromatosis, thalassemia and other forms of severe anemias. The magnetic iron detector (MID) is a room-temperature susceptometer, which measures the total iron overload in the liver. Since February 2005, about 600 patients have been assessed using this device. The iron overload is obtained by calculating the difference between the measured magnetization signal of the patient and the patient's background signal. The latter is the magnetization signal that the patient would generate with normal iron content. This study presents the method for calculating the background signal of healthy volunteers and the application of the same method to patients with iron burden in order to evaluate their overload. The present MID sensitivity is 0.8 g and the reproducibility of the iron overload measurement of the same patients is lower than 0.5 g. The MID does not require calibration with liver biopsies. We correlated the MID measurements with the results of 26 biopsies (R = 0.62), 64 superconducting quantum interference device susceptometer measurements (R = 0.79), 666 serum ferritin concentration measurements (R = 0.72), and 41 MRI- R2* measurements (R = 0.71).

We conducted the first nation-wide cohort study of sickle cell disease (SCD) in Italy, a Southern European country exposed to intense recent flux migration from endemic areas for SCD. We evaluate the impact of hydroxyurea on a total of 652 pediatric and adult patients from 33 Reference Centers for SCD (mean age 24.5±15years, 51.4% males). Hydroxyurea median treatment duration was 7years (range: <1year to 29years) at a mean therapeutic dose of 18±4.7mg/kg/day. Hydroxyurea was associated with a significant increase in mean total and fetal hemoglobin and a significant decrease in mean hemoglobin S, white blood and platelet counts, and lactate dehydrogenase levels. Hydroxyurea was associated with a significant reduction in the incidence of acute chest syndrome (-29.3%, p<0.001), vaso-occlusive crisis (-34.1%, p<0.001), hospitalization (-53.2%, p<0.001), and bone necrosis (-6.9%, p<0.001). New silent cerebral infarction (SCI) occurred during treatment (+42.4%, p<0.001) but not stroke (+0.5%, p=0.572). These observations were generally consistent upon stratification for age, descent (Caucasian or African), genotype (βS/βS, βS/β or βS/β) and duration of treatment (< or ≥10years). There were no new safety concerns observed compared to those commonly reported in the literature. Our study, conducted on a large population of patients with different descent and compound state supports the benefits of hydroxyurea therapy as a treatment option. Registered at clinical trials.gov (NCT02709681).

An accurate assessment of body iron accumulation is essential for the diagnosis and therapy of iron overload in diseases such as thalassemia or hemochromatosis. Magnetic iron detector susceptometry and MRI are noninvasive techniques capable of detecting iron overload in the liver. Although the transverse relaxation rate measured by MRI can be correlated with the presence of iron, a calibration step is needed to obtain the liver iron concentration. Magnetic iron detector provides an evaluation of the iron overload in the whole liver. In this article, we describe a retrospective observational study comparing magnetic iron detector and MRI examinations performed on the same group of 97 patients with transfusional or congenital iron overload. A biopsy‐free linear calibration to convert the average transverse relaxation rate in iron overload (R2 = 0.72), or in liver iron concentration evaluated in wet tissue (R2 = 0.68), is presented. This article also compares liver iron concentrations calculated in dry tissue using MRI and the existing biopsy calibration with liver iron concentrations evaluated in wet tissue by magnetic iron detector to obtain an estimate of the wet‐to‐dry conversion factor of 6.7 ± 0.8 (95% confidence level). Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.

Background The correlation between thalassemia and malignancies other than hepatocellular carcinoma (HCC) and the possible relationship between other hemoglobinopathies and tumor risk have been poorly evaluated. Methods Eight Italian specialized centers evaluated the incidence of malignant neoplasms in hemoglobinopathies as well as their sites and features. The study cohort included 4631 patients followed between 1970 and 2021 (transfusion‐dependent β‐thalassemia, 55.6%; non–transfusion‐dependent thalassemia, 17.7%; sickle cell disease, 17.6%; hemoglobin H disease, 8.3%). Results A total of 197 diagnoses of cancer were reported (incidence rate, 442 cases per 100,000 person‐years). The liver was the most frequent site of tumors in both sexes, with a higher incidence (190 cases per 100,000 person‐years) in comparison with the general population found in all types of hemoglobinopathies (except hemoglobin H disease). In recent years, tumors have become the second cause of death in patients with transfusion‐dependent thalassemia. A lower risk of breast and prostate cancer was observed in the whole group of patients with hemoglobinopathies. The first cancer diagnoses dated back to the 1980s, and the incidence rate sharply increased after the 2000s. However, although the incidence rate of cancers of all sites but the liver continued to show an increasing trend, the incidence of HCC showed stability. Conclusions These findings provide novel insights into the relationship between cancer and hemoglobinopathies and suggest that the overall risk is not increased in these patients. HCC has been confirmed as the most frequent tumor, but advances in chelation and the drugs that have led to the eradication of hepatitis C may explain the recent steadiness in the number of diagnoses that is reported here.

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