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Deferasirox improves liver fibrosis in beta‐thalassaemia major patients. A five‐year longitudinal study from a single thalassaemia centre

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Beta-thalassaemia major patients often develop liver fibrosis due to transfusion-related iron overload, increased intestinal iron absorption and/or hepatitis C virus (HCV) infection (Deugnier et al, 2011). The present study aimed… Click to show full abstract

Beta-thalassaemia major patients often develop liver fibrosis due to transfusion-related iron overload, increased intestinal iron absorption and/or hepatitis C virus (HCV) infection (Deugnier et al, 2011). The present study aimed to prospectively evaluate the liver fibrosis status in beta-thalassaemia major patients being chelated with deferasirox only and explore the contribution of iron overload in liver fibrosis. The study took place at Adults Thalassaemia Unit, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece. We conducted a prospective five-year (2008–2013) follow-up study in 22 beta-thalassaemia major patients (9 males/ 13 females) with a median age of 32 (20–47) years. All patients were on regular transfusion regimen, maintaining a pre-transfusion haemoglobin level >95 g/l, and deferasirox chelation therapy was chosen for optimized treatment adherence. All patients were negative by polymerase chain reaction for HCVRNA and had no other characteristics, comorbidities or medications of known effect on transient elastography liver stiffness measurement (Ferraioli et al, 2015; Chang, 2016). During the study period, seven female patients discontinued deferasirox chelation for 16 (12–18) months due to successful pregnancies but restarted deferasirox 12 (8–16) months before the second fibrosis evaluation. Patients were assessed with transient elastography at baseline—within 35 (5–47) days after having been switched to 35 (30–40) mg/kg deferasirox—and re-examined at five years with the same method by the same operator, who was blinded to the rest of the medical history and laboratory studies of each patient. Transient elastography was performed with use of FibroScan (Echosens, Paris, France) as per the manufacturer’s recommendations and the relevant clinical guidelines (Ferraioli et al, 2015). Liver stiffness measurements are expressed in Kilopascals (kPa). Serum ferritin levels, liver and cardiac T2* magnetic resonance imaging (MRI) were concurrently run for the evaluation of iron overload. The determination of serum ferritin was performed with the ARCHITECT ferritin assay (Abbott Laboratories, Lake Bluff, IL, USA) using Architect i system (Abbott Laboratories) according to the manufacturer’s instructions. Magnetic resonance images were acquired using the Philips Intera 1 5T MRI system (Koninklijke Philips N.V., Amsterdam, The Netherlands) with use of the previously validated protocol provided by Anderson et al (2001). Descriptive analysis is expressed as the mean and standard deviation. Comparison between measurements at the baseline and measurements at the five-year follow-up was performed with use of the paired samples t-test. Multiple regression analysis was performed on the five-year liver stiffness measurements change, to assess the effect of gender, age, ferritin change, liver and cardiac T2* MRI differences, as well as iron chelation pattern (intermittent vs continuous). The assumptions checking procedure showed two significantly lower outliers on the ferritin change values that were influencing the results of the analysis. These two patients were excluded from the analysis. The results are reported after checking for their validity on the whole set of patients. All statistical analyses were performed using two-tailed significance tests with the level of significance set at 0 05. Analysis was carried out with use of the IBM SPSS , Version 21.0 software (IBM Corporation, Armonk, NY, USA). The main results of the study, including the descriptive analysis of the study sample as well as the multivariable regression analysis, are reported in Table I, Fig 1 and Data S1. The results of the present study stress that uninterrupted iron chelation with deferasirox could offer significant improvement in liver fibrosis as assessed by means of transient elastography. The change in five-year liver stiffness measurements was significantly affected by the chelation intake pattern irrespective of age, gender, ferritin changes, and liver and cardiac T2* MRI differences (b = 2 806, P = 0 005). Moreover, the group of patients on continuous deferasirox chelation achieved significantly reduced transient elastography values between baseline and follow-up measurements at five years (z = 2 26, P = 0 024). This is also in line with better control of iron overload as shown by the improvement in T2* MRI obtained liver iron concentration during the same period, although this was not statistically significant. Repeating the analysis to take into account the parameters of non-pregnant females vs pregnant females and males vs pregnant females confirmed the above mentioned results (Table I). Of note, a major limitation of the study is the small number of patients taken into consideration. Therefore, despite high significance, cautious interpretation of the above-mentioned results is required. Notably, the results of the present study are partially in accordance with the relevant literature regarding chelation with deferasirox. In the last decade, it has been shown that Correspondence

Keywords: thalassaemia; liver fibrosis; analysis; study; five year

Journal Title: British Journal of Haematology
Year Published: 2018

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