Iron deficiency is a prevalent public health problem in our country and in the world. It is particularly an important threat for the pediatric age group. It is believed that evaluation of ERFE and hepcidin levels in patients with iron deficiency anemia will provide a guide for new treatment methods in the future.
When Group III was compared against GROUP I and Group II in the present study, hemoglobin, MCV, MCH, MCHC, iron, and ferritin values were found to be significantly low in Group I. Besides, RDW value was determined to be significantly high in the iron deficiency group compared to the control group. These findings overlap with laboratory findings regarding iron deficiency anemia.
As the essential regulator of systemic iron balance, hepcidin transcription in the liver is controlled by a complicated signal interaction such as evident inflammation, iron status, and erythropoietic triggering (13). The iron in the circulation and tissues increases hepcidin level in order to restrain more iron intake, and erythropoietic activity suppresses hepcidin in order to increase the usability of iron for erythrocyte production (14).
In iron deficiency, hepcidin decreases and iron absorption increases, which leads to iron release from deposits (15). In a study conducted by Semercioglu et al., hepcidin levels were found to be significantly lower in children with iron deficiency anemia compared to the children without iron deficiency anemia (17). In parallel with the said study and the literature, in the present study, hepcidin level was found to be significantly lower in the iron deficiency group in comparison to the control group.
Hepcidin also functions as a mediator in host defense. During infections, cytokines increase (especially interleukin), hepcidin level increases very fast, and this leads to an acute decrease in plasma iron concentration (15). Decreased plasma and non-cellular iron concentration restrain the required iron supply for infectious agents (15). Inflammation anemia is characterized by high hepcidin concentrations stimulated by inflammatory cytokines (15). In a study conducted on children with inflammatory intestine disease, a positive correlation was found between hepcidin and ferritin (16). Similarly, in the present study, a strong correlation was determined between ferritin and hepcidin, but no correlation was found with other laboratory parameters. This may suggest that hepcidin is largely regulated by iron deposit level.
In the comparison between Group I and Group II in terms of values following one-month treatment, significant increases were observed in erythrocyte count, hemoglobin, hematocrit, MCV, MCHC, iron, ferritin, and hepcidin levels. Iron binding capacity, on the other hand, displayed a significant decrease.
In cases of recurring blood loss, hepcidin is suppressed by erythroferrone and it allows more iron absorption which is required for the recovery of anemia (15). Ganz et al. found a negative correlation between ERFE and hepcidin concentrations (18). On the other hand, in another study, no correlation was found between plasma ERFE and hepcidin concentrations (19). In the present study, no correlation was determined between ERFE and hepcidin concentrations.
In another study, ERFE concentrations of individuals with iron deficiency were found to be higher compared to ERFE concentrations of the control group individuals (20). In the said study, a negative correlation was shown between ERFE and ferritin concentrations. These researchers could not demonstrate a relationship between hepcidin and ERFE as they did not measure hepcidin values (20). In the present study, no correlation was found between hepcidin and erythroferrone as well as between ferritin and erythroferrone.
In a similar study to the present study conducted by Xu LH et al., when serum hepcidin levels were examined between women who gave birth to children with IDA and women who gave birth to children without IDA, it was determined that hepcidin significantly decreased in the iron deficiency group, but that there was no significant difference between the two groups in terms of erythroferrone levels (21). In studies conducted, it has been reported that iron deposits reached maximum level in 2–3 months after the beginning of the treatment (22). In the present study, no significant change was found in erythroferrone levels. It is thought that this may have resulted from the short duration iron treatment provided to the patients with iron deficiency anemia included in the study.
If the suppressive role and effective mechanism of ERFE on hepcidin can be clarifiedas a result of the studies to be conducted in the future, antibodies specific to ERFE can be produced. More detailed studies are needed in order to reveal the role of ERFE in iron metabolism.
The present study is important in that it covered childhood period when iron deficiency is observed the most. The study has provided guidance in terms of making sense of the parameters examined. Iron deficiency anemia treatment is a long-term treatment. The limitations of the study are collecting the second repetition samples in a short period of one month, the low number of cases, and not including patients with severe anemia in the study.
In conclusion, in the study, it was determined that serum hepcidin level decreased in iron deficiency anemia, provided that there was no inflammatory processes. The positive and strong correlation found between hepcidin and ferritin suggested that iron deposits could be effective in iron balance. Not determining a significant difference in serum erythroferrone levels between the control group and the iron deficiency group suggested that erythroferrone may not play a role in the regulation of iron metabolism in children with mild and moderate iron deficiency anemia.