Hepcidin as a Therapeutic Target in Liver Cirrhosis: A Cohort Study on Iron Dysregulation
DOI:
https://doi.org/10.36283/ziun-pjmd14-2/004Keywords:
Hepcidin, Liver Cirrhosis, Iron Overload, Ferritin, Liver Function, Cirrhosis, ComplicationsAbstract
Background: Iron metabolism dysregulation in liver cirrhosis leads to iron accumulation which triggers oxidative stress and advances liver tissue damage. This study investigated how Hepcidin modulation affects iron accumulation and liver function alongside cirrhosis complications among liver cirrhosis patients.
Methods: Researchers conducted a prospective cohort study (January 2024 to January 2025) by monitoring 120 liver cirrhosis patients at Asian Institute of Medical Sciences Hyderabad and remaining from Liaquat University Hospital Jamshoro (ERC/9303/24) in adherence with the Declaration of Helsinki. The study documented both baseline clinical data alongside liver function tests and Hepcidin measurements. Two separate groups were formed through randomization for treatment with Hepcidin-modulating. Disease severity using Child-Pugh and MELD scores was determined. The study used both Kaplan-Meier survival and Cox regression methods to examine clinical outcomes. Data were analyzed using SPSS version 22. Paired t-tests evaluated within-group changes, and one way ANOVA was employed for between-group comparisons (p-value<0.05, Statistical Significance).
Results: The intervention group experienced a substantial Hepcidin level rise from 45.7 ng/mL to 87.5 ng/mL. The levels of serum ferritin declined from 890.5 ng/mL to 510.2 ng/mL. The intervention group achieved notable liver function improvement through their Child-Pugh score drop from 8.2 to 6.5 (p=0.003) and their MELD score reduction from 18.2 to 14.9 (p=0.002).
Conclusion: The modulation of Hepcidin treatment leads to major reductions in iron burden while also supporting improved liver function and lowering cirrhosis-related complications among liver cirrhosis patients.
References
Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of non-alcoholic fatty liver disease—Meta-analytic assessment of prevalence, incidence, and outcomes. J Hepatol. 2016 Apr;64(4):731-740. doi:10.1016/j.jhep.2015.11.014.
Liu Y, Li G, Lu F, Guo Z, Cai S, Huo T. Excess iron intake induced liver injury: The role of gut-liver axis and therapeutic potential. Biomed Pharmacother. 2023 Dec;168:115728. doi:10.1016/j.biopha.2023.115728.
Billesbølle CB, Azumaya CM, Kretsch RC, Powers AS, Gonen S, Schneider S, et al. Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms. Nature. 2020 Oct;586(7831):807-811. doi:10.1038/s41586-020-2668-z.
Nemeth E, Ganz T. Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis. Int J Mol Sci. 2021 Jun 17;22(12):6493. doi:10.3390/ijms22126493.
Camaschella C, Nai A, Silvestri L. Iron metabolism and iron disorders revisited in the hepcidin era. Haematologica. 2020 Feb;105(2):260-272. doi:10.3324/haematol.2019.232124.
Ganz T. Hepcidin and its role in regulating systemic iron metabolism. Hematology Am Soc Hematol Educ Program. 2011;2011(1):507-511. doi:10.1182/asheducation-2011.1.507.
Ganz T, Nemeth E. Hepcidin therapy for disorders of iron metabolism. Biochim Biophys Acta Mol Cell Res. 2012 Sep;1823(9):1434-1443. doi:10.1016/j.bbamcr.2012.01.014.
Neves JV, Gomes AC, Costa DM, Barroso C, Vaulont S, Cordeiro da Silva A, Tavares J, Rodrigues PNS. A role for hepcidin in the anemia caused by Trypanosoma brucei infection. Haematologica. 2021 Mar 1;106(3):806-818. doi:10.3324/haematol.2019.227728.
Lanser L, Fuchs D, Kurz K, Weiss G. Physiology and Inflammation Driven Pathophysiology of Iron Homeostasis-Mechanistic Insights into Anemia of Inflammation and Its Treatment. Nutrients. 2021 Oct 22;13(11):3732. doi:10.3390/nu13113732.
Saboor M, Zehra A, Hamali HA, Mobarki AA. Revisiting Iron Metabolism, Iron Homeostasis and Iron Deficiency Anemia. Clin Lab. 2021 Mar 1;67(3). doi:10.7754/Clin.Lab.2020.200742.
Longo M, Paolini E, Meroni M, Dongiovanni P. Remodeling of Mitochondrial Plasticity: The Key Switch from NAFLD/NASH to HCC. Int J Mol Sci. 2021 Apr 17;22(8):4173. doi:10.3390/ijms22084173.
Leung AKC, Lam JM, Wong AHC, Hon KL, Li X. Iron Deficiency Anemia: An Updated Review. Curr Pediatr Rev. 2024 Jan;20(3):339-356. doi:10.2174/1573396320666230727102042.
Joachim JH, Mehta KJ. Hepcidin in hepatocellular carcinoma. Br J Cancer. 2022 Jul;127(2):185-192. doi:10.1038/s41416-022-01753-2.
Lo JO, Benson AE, Martens KL, Hedges MA, McMurry HS, DeLoughery T, et al. The role of oral iron in the treatment of adults with iron deficiency. Eur J Haematol. 2023 Sep;110(2):123-130. doi:10.1111/ejh.13892.
Billesbølle CB, Azumaya CM, Kretsch RC, Powers AS, Gonen S, Schneider S, et al. Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms. Nature. 2020 Oct;586(7831):807-811. doi:10.1038/s41586-020-2668-z.
Ohta K, Ito M, Chida T, Nakashima K, Sakai S, Kanegae Y, et al. Role of hepcidin upregulation and proteolytic cleavage of ferroportin 1 in hepatitis C virus-induced iron accumulation. PLoS Pathog. 2023 Aug 16;19(8):e1011591. doi:10.1371/journal.ppat.1011591.
Xiong H, Zhang C, Han L, Xu T, Saeed K, Han J, et al. Suppressed farnesoid X receptor by iron overload in mice and humans potentiates iron-induced hepatotoxicity. Hepatology. 2022;76(2):387-403. doi: 10.1002/hep.32270.
Xu Y, Alfaro-Magallanes VM, Babitt JL. Physiological and pathophysiological mechanisms of hepcidin regulation: clinical implications for iron disorders. Br J Haematol. 2021 May;193(5):882-893. doi: 10.1111/bjh.17252.
Praeger-Jahnsen L, Magnussen K, Schiødt FV, Therkildsen RC, Jørgensen N, Friis-Hansen L. A novel hepcidin mutation. Transfus Clin Biol. 2023 Sep;30(3):335-340. doi: 10.1016/j.tracli.2023.03.001.
Lanser L, Fuchs D, Kurz K, Weiss G. Physiology and inflammation-driven pathophysiology of iron homeostasis—mechanistic insights into anemia of inflammation and its treatment. Nutrients. 2021 Nov;13(11):3732. doi: 10.3390/nu13113732.
Migone De Amicis M, Rimondi A, Elli L, Motta I. Acquired refractory iron deficiency anemia. Mediterr J Hematol Infect Dis. 2021 Jan;13(1):e2021028. doi: 10.4084/MJHID.2021.028.
Cabrera E, Crespo G, VanWagner LB. Diagnosis and management of hereditary hemochromatosis. JAMA. 2022 Nov;328(18):1862-1863. doi: 10.1001/jama.2022.17727.
Sagar P, Angmo S, Sandhir R, Rishi V, Yadav H, Singhal NK. Effect of hepcidin antagonists on anemia during inflammatory disorders. Pharmacol Ther. 2021 Sep;226:107877. doi: 10.1016/j.pharmthera.2021.107877.
Kouroumalis E, Tsomidis I, Voumvouraki A. Iron as a therapeutic target in chronic liver disease. World J Gastroenterol. 2023 Jan;29(4):616-655. doi: 10.3748/wjg.v29.i4.616.
Zheng H, Yang F, Deng K, Wei J, Liu Z, Zheng YC, et al. Relationship between iron overload caused by abnormal hepcidin expression and liver disease: a review. Medicine (Baltimore). 2023 Mar;102(11):e33225. doi: 10.1097/MD.0000000000033225.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Pakistan Journal of Medicine and Dentistry
This work is licensed under a Creative Commons Attribution 4.0 International License.
This is an open-access article distributed under the terms of the CreativeCommons Attribution License (CC BY) 4.0 https://creativecommons.org/licenses/by/4.0/
