Introduction
Thalassemia syndromes are hereditary disorders in the production of α and β globin chains in the hemoglobin tetramer structure. In β-thalassemia patients, the incomplete production of β-globin by disrupting the production of sufficient amounts of HbA leads to the formation of small red blood cells (microcytosis) and containing low amounts of hemoglobin (hypochromia). On the other hand, due to the disturbance created in the balance of α and β globin chains, α-globin chains are unpaired and excessively accumulated, and by forming toxic deposits, it causes severe damage to the membrane of red blood cells and erythroid precursors (microcytic hypochromic anemia). As a result of this damage to blood cells, ineffective erythropoiesis occurs to compensate for anemia in the body which, in addition to producing a few red blood cells with a short lifespan, causes iron overload in the body by increasing the absorption of dietary iron. According to the statistics reported by the World Health Organization (WHO) in 2008, about 40,000 babies with β-thalassemia are born every year, and 25,500 of them depend on regular blood transfusions for their survival. Long-term blood transfusion in β-thalassemia major patients doubles the possibility of iron overload in the body of these patients. In the absence of appropriate treatment with iron chelators (iron overload treating drugs), it may lead to the death of patients in the second or third decade of life due to heart, endocrine and liver failure caused by secondary hemochromatosis. This study aims to determine the effect of iron removal with deferasirox in β-thalassemia patients treated with regular blood transfusions on the level of ferritin and liver aminotransferases.

Methods
In this analytical cross-sectional study, the changes in the serum level of liver enzymes in β-thalassemia patients receiving deferasirox in the thalassemia department of Hefdeh Shahrivar Hospital and in the Be’sat Clinic in Rasht, Iran, were retrospectively investigated. For this reason, 104 β-thalassemia patients dependent on regular blood draws, aged over 2 years, who were treated with deferasirox as an iron chelator for at least two consecutive years, were selected. The SPSS software (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. The normality of the data was examined by the Kolmogorov-Smirnov test. If the data were normal, the paired t-test would be used; otherwise, the Mann-Whitney U test would be used. Comparison of qualitative variables was done by chi-square test and, if necessary, Fisher’s exact test. P<0.05 was considered as a statistically significant.

Results
Among 104 patients included in the study, 44(42.3%) were male and 60(57.7%) were female, in the age range of 5-46 years (mean age=24.25±8.79 years). Blood transfusions had been performed for 27 patients (26%) with intervals of less than three weeks and for 77 patients (74%) with intervals of more than three weeks (mean blood transfusion interval=27.09±7.04 days). Deferasirox had been used by 53 patients (51%) for 2-5 years and by 51 patients (49%) for more than 5 years (mean duration of treatment by deferasirox=5.54±1.45 years). Deferasirox dosage in 38 patients (36.5%) was less than 32 mg/kg/day and in 66 patients (63.5%) more than 32 mg/kg/day (mean dosage 32.3±82.58 mg/kg/day).
Statistically, there was a significant difference in the reduction of serum ferritin (P=0.017), AST (P=0.0001) and ALT (P=0.015) in the last blood test after starting deferasirox treatment, compared to baseline levels. In terms of gender, there was a statistically significant difference in serum AST level before and after taking the drug compared to baseline in both males (P=0.0001) and females (P=0.004). Also, a statistically significant difference was observed in the ALT serum level before and after taking the drug in both males (P=0.006) and females (P=0.024).
In terms of age range, there was a statistically significant difference in the serum AST level before and after taking the drug in the age groups of <15 years (P=0.026), 15-30 years (P=0.003) and >30 years (P=0.001). In the serum ALT level, there was a significant difference in the age groups of 15-30 years (P=0.04) and >30 years (P=0.001).
In terms of blood transfusion intervals, there was a statistically significant difference in the level of serum AST before and after taking the drug in blood recipients with interval of >3 weeks (P=0.001). In the serum ALT level, there was a significant difference in blood recipients with interval of <3 weeks (P=0.031) and >3 weeks (P=0.01).
Regarding the duration of deferasirox use, there was a statistically significant difference in the serum AST level before and after taking the drug in the groups <5 years (P=0.002) and >5 years (P=0.0001). There was also a significant difference in the serum ALT level in the groups <5 years (P=0.016) and >5 years (P=0.012).
In terms of deferasirox dosage, there was a statistically significant difference in the serum AST level before and after taking the drug in the groups <32 mg/kg/day (P=0.012) and >32 mg/kg/day (P=0.0001). In the serum ALT level, there was a significant difference in the dosage group of >32 mg/kg/day (P=0.003).

Conclusion
In this study, the use of deferasirox not only led to a slight increase in liver enzymes, but also a significant decrease in serum ferritin and transaminase levels in β-thalassemia patients dependent on blood transfusion. It seems that deferasirox consumption after a few months, although causes mild and rare liver complications, can play a protective role for the liver against iron overload in the body and lead to a decrease in the level of liver aminotransferases. In this study, the greatest decrease in the level of liver transaminases following deferasirox intake was found in males, age group >30 years, those with blood transfusion interval >3 weeks, those with duration of drug use >5 years, and those with drug dosage >32 mg/kg/day. However, the efficacy of this iron chelator in reducing the level of liver enzymes was not significantly different between patients in terms of age, sex, interval of blood transfusion, duration of use, or dosage. Considering some discrepancies among various studies, for more accurate determination of the capability of non-invasive diagnostic methods (including liver aminotransferases and MRI) in showing the harmful effects of iron overload and deferasirox on the liver, more extensive evidence-based studies in β-thalassemia patients are needed.

Ethical Considerations
Compliance with ethical guidelines
This study was approved by the Ethics Committee in Biological Research of Guilan University of Medical Sciences (Code: IRGUMS.REC.1397.092).

Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors.

Authors' contributions
Conceptualization and methodology: Bahram Darbandi, Soodeh Salehi, Shayan Pourkazem and Mohammadreza Sharifi Rad; Validation and analysis: Adel Baghersalimi, Mercedeh Enshaei and Mohammadreza Sharifi Rad; Visualization and investigation: Shayan Pourkazem; Initial draft preparation: Mohammadreza Sharifi Rad and Shayan Pourkazem; Review and editing: Bahram Darbandi, and Shayan Pourkazem; Supervision: Vahid Aminzadeh, Behrang Motamed, Adel Baghersalimi, and Bahram Darbandi; Project administration: Bahram Darbandi; Resources: Mohammadreza Sharifi Rad.

Conflicts of interest
The authors declared no conflict of interest.

Acknowledgements
The authors express their gratitude to Afaq Hassan Zadeh Rad and Reza Bayat, the esteemed colleagues of the Children's Diseases Research Center, Guilan University of Medical Sciences Rasht, Guilan.


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