Hepcidin levels, markers of iron overload, and liver damage in children with beta-thalassemia major
Abstract
Background Thalassemia is a hemoglobin synthesis disorder that causes patients to need lifelong blood transfusions, leading to iron overload and alter organ function, including the liver. Hepcidin, produced by the liver, plays a role in iron homeostasis and should be increased in excess iron stores. However, the level decreases in thalassemia due to some factors, such as ineffective erythropoiesis and liver damage. Recent publications revealed that hepcidin could be associated with iron overload and also a marker of liver diseases.
Objective To analyse the correlation between hepcidin level, markers of iron overload, and liver damage in beta-thalassemia major.
Methods This cross-sectional study included all ?-thalassemia major age 2-18 years admitted to Dr. Mohammad Hoesin Hospital, Palembang, South Sumatera, who underwent blood transfusions from March to August 2022. We measured the level of iron overload markers, hepcidin, liver function test (LFT), and performed liver ultrasonography (USG).
Results Of 97 subjects, median hepcidin level was 10.01 ng/mL and 68% of the subjects showed a decrease. The iron overload parameters were evaluated from serum iron levels (P=0.13), ferritin levels (P=0.90), and transferrin saturation (P=0.29) and 24.7% had abnormal liver USG findings. Spearman’s correlation revealed that only direct bilirubin (DB) (r=0.35; P=0.001) and liver USG (r=0.20; P=0.05) had positive correlations with decreased levels of hepcidin. Also, it had 91.7% sensitivity in predicting liver damage from ultrasound.
Conclusion The hepcidin level was not significantly associated with iron overload markers.
References
2. Kementerian Kesehatan Republik Indonesia. Pedoman nasional pelayanan kedokteran dan tata laksana talasemia. Jakarta: Kemenkes RI; 2018. p. 4-90. Available from: http://hukor.kemkes.go.id/uploads/produkhukum/KMK_No.HK.01_.07- MENKES-1
3. Direktorat Pencegahan dan Pengendalian Penyakit Tidak Menular, Kementerian Kesehatan Republik Indonesia. Angka pembawa sifat talasemia tergolong tinggi. [cited 11 November 2021]. Available from: https://p2ptm.kemkes.go.id/tag/angka-pembawa-sifat-talasemia-tergolong-tinggi
4. Divisi Hematoonkologi RSUP Dr. Moh. Hoesin Palembang. Register pasien talasemia. (unpublished).
5. Patel S, Siddiqui A, Kareem I. A correlative study of serum bilirubin and liver enzymes with serum ferritin in beta thalassemia major. J Dent Med Sci. 2018;17:62–7. DOI: https://doi.org/10.9790/0853-1701026267
6. Wahidiyat PA, Iskandar SD, Rahmartani D, Sekarsari D. Liver iron overload and hepatic function in children with thalassemia major. Paediatr Indones. 58:2018;233-7. https://doi.org/10.14238/pi58.5.2018.233-7
7. Kali A, Charles MVP, Seetharam RSK. Hepcidin - A novel biomarker with changing trends. Pharmacogn Rev. 2015;9:35-40. DOI: https://doi.org/10.4103/0973-7847.156333
8. Ginzburg Y, Rivella S. ?-thalassemia: a model for elucidating the dynamic regulation of ineffective erythropoiesis and iron metabolism. Blood. 2011;118:4321-30. DOI: https://doi.org/10.1182/blood-2011-03-283614
9. Xu Y, Alfaro-Magallanes VM, Babitt JL. Physiological and pathophysiological mechanisms of hepsidin regulation: clinical implications for iron disorders. Br J Haematol. 2021;193:882-93. DOI: https://doi.org/10.1111/bjh.17252
10. Risum M, Barfod T, Raaschou-Jensen K. Transient elastography for the detection of hepatic iron overload in patients with myelodysplastic syndrome. Eur Oncol Haematol. 2016;12:103–6. DOI: https://touchoncology.com/transient-elastography-for-the-detection-of-hepatic-iron-overload-in-patients-with-myelodysplastic-syndrome-2/
11. Delima RD, Chua ACG, Tirnitz-Parker JEE, Gan EK, Croft KD, Graham RM, et al. Disruption of hemochromatosis protein and transferrin receptor 2 causes iron-induced liver injury in mice. Hepatology. 2012;56:585–93. DOI: https://doi.org/10.1002/hep.25689
12. An P, Wang H, Wu Q, Guo X, Wu A, Zhang Z, et al. Elevated serum transaminase activities were associated with increased serum levels of iron regulatory hormone hepcidin and risk of hyperferritinemia. Sci Rep. 2015;5:13106. DOI: https://doi.org/10.1038/srep13106
13. Tantiworawit A, Khemakapasiddhi S, Rattanathammethee T, Hantrakool S, Chai- Adisaksopha C, Rattarittamrong E, et al. Correlation of hepcidin and serum ferritin levels in thalassemia patients at Chiang Mai University Hospital. Biosci Rep. 2021;41. DOI: https://doi.org/10.1042/BSR20203352
14. Enomoto M, Morikawa H, Tamori A, Kawada N. Noninvasive assessment of liver fibrosis in patients with chronic hepatitis B. World J Gastroenterol. 2014;20:12031–8. DOI: https://doi.org10.3748/wjg.v20.i34.12031
15. Tomic D, Kemp WW, Roberts SK. Nonalcoholic fatty liver disease: current concepts, epidemiology and management strategies. Eur J Gastroenterol Hepatol. 2018;30:1103–15. DOI: https://doi.org/10.1097/MEG.0000000000001235
16. Wong T, Wong RJ, Gish RG. Diagnostic and treatment implications of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Gastroenterol Hepatol (N Y). 2019;15:83–9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469262/pdf/GH_15_83.pdf
17. Kumar S, Bhatia P, Jain R, Bharti B. Plasma hepsidin levels in healthy children: review of current literature highlights limited studies. J Pediatr Hematol Oncol. 2019;41:238-42. DOI: https://doi.org/10.1097/MPH.0000000000001216
18. Jaya IK, Sari DP, Zen NF. Gambaran usia tulang pada pasien talasemia dengan perawakan pendek di bagian ilmu kesehatan anak RSUP Dr. Moh Hoesin Palembang. Jurnal Kedokteran dan Kesehatan FK UNSRI. 2015:2:217-22. ISSN (Print): 2406-7431
E-ISSN (Online) : 2614-0411.
19. Tantiworawit A, Khemakapasiddhi S, Rattanathammethee T, Hantrakool S, Chai- Adisaksopha C, Rattarittamrong E, et al. Correlation of hepsidin and serum ferritin levels in talasemia patients at Chiang Mai University Hospital. Biosci Rep 2021;41(2):1-8. DOI: https://doi.org/10.1042/BSR20203352
20. Gardenghi s, Ramos P, Marongiu MF, Melchiori L, Breda L, Guy E, et al. Hepcidin as a therapeutic tool to limit iron overload and improve anemia in beta-thalassemic mice. J Clin Invest. 2010;120(12):4466-77. DOI: https://doi.org/10.1172/JCI41717
21. Agustina R, Mandala Z, Indah RN. Hubungan kadar feritin serum dengan kadar enzim SGOT dan SGPT pada pasien thalasemia ? mayor Jurnal Ilmiah Kesehatan Sandi Husada. 2020:11:252-7. DOI: https://doi.org/10.35816/jiskh.v11i1.258
22. Jagadishkumar K, Yerraguntla, N. Vaddambal MG. Serum hepcidin levels in children with beta thalassemia major. [cited 2023 Nov 30]. Indian Pediatr. 2018; 55:911-2. Available from: https://www.indianpediatrics.net/oct2018/911.pdf
23. Al-Moshary M, Imtiaz N, Al-Mussaed E, Khan A, Ahmad S, Albqami S. Clinical and biochemical assessment of liver function test and its correlation with serum ferritin levels in transfusion-dependent thalassemia patients. Cureus. 2020;12:e7574. DOI: https://doi.org/10.7759/cureus.7574
24. Kaddah Ahmad Maher, Amin abdel Salam, Marwa Salah Farhan, Reham Ragab. Serum hepcidin as a diagnostic marker of severe iron overload in beta thalassemia major. Indian J Pediatr. 2017;84:745-50. DOI: https://doi.org/10.1007/s12098-017-2375-4
25. Shah FT, Ali SM, Shahid A, Dilawar M, Rafi T. Correlation between serum ferritin levels and the extent of liver damage in patients with beta thalassemia major. Cureus 2018; 10(8): e3156. DOI: https://doi.org/10.7759/cureus.42069
26. Saad HKM, Taib WRW, Ismail I, Johan MF, Al Wajeeh AS, Al Jamal HAN. Reduced hepcidin expression enhances iron overload in patients with HbE/? thalassemia: a comparative cross sectional study. Exp Ther Med. 2021;22:1402. DOI: https://doi.org/10.3892/etm.2021.10838
27. Agustina R, Mandala Z, Indah RN. Hubungan kadar feritin serum dengan kadar enzim sgot dan sgpt pada pasien thalasemia ? mayor. Jurnal Ilmiah Kesehatan Sandi husada 2020:9:252-7. DOI: https://doi.org/10.35816/jiskh.v11i1.258
28. Hossaini SKE, Haeri MR. Association between serum levels of hepcidin and ferritin in patients with thalassemia major and intermedia, the role of iron chelator. J Hematopathol. 2019;12:143-7. DOI: https://doi.org/10.1007/s12308-019-00363-x
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Accepted 2024-10-14
Published 2024-10-14
