Contents lists available at ScienceDirect Journal of Trace Elements in Medicine and Biology journal homepage: www.elsevier.com/locate/jtemb Clinical studies Ferritin and liver fibrosis among patients with chronic hepatitis C virus infection Candelaria Martín-González*, Ricardo Pelazas-González, Camino Fernández-Rodríguez, Remedios Alemán-Valls, Antonio Martínez-Riera, Paula Ortega-Toledo, Alen García-Rodríguez, Melchor Rodríguez-Gaspar, Emilio González-Reimers 1 Servicio de Medicina Interna. Hospital Universitario de Canarias. Universidad de La Laguna. Tenerife, Canary Islands, Spain ARTICLE INFO Keywords: HCV Chronic hepatitis C Iron Ferritin Transferrin Liver fibrosis ABSTRACT Introduction: In chronic hepatitis C virus (HCV) infection there is increased iron absorption leading to iron overload, a fact that may promote ferritin synthesis. Theoretically, increased ferritin should promote ongoing liver fibrosis but disparate results have been described. Objective: We analyze the behavior of iron metabolism- related variables, comparing them with fibrosis and inflammatory activity in liver biopsy in HCV infected patients. Patients and Methods: We analyzed among 90 HCV patients subjected to liver biopsy prior to antiviral treatment the relationships of serum levels of iron, ferritin, transferrin, transferrin saturation index (TSI) and total iron binding capacity (TIBC) with liver fibrosis and histological severity, assessed by Metavir-f, Metavir-a and Knodell indices, as well as with liver function, and also compared the aforementioned iron metabolism- related variables with 34 controls. Results: Patients showed higher values of sideremia (T = 2.04; p = 0.044) and transferrin (T = 2.29; p = 0.004) compared with controls; but not ferritin, that was significantly higher among the 33 patients who also consumed alcohol (Z = 2.05; p = 0.041). Most patients showed a well preserved liver function (86 cases, Child A). Patients with Child B or C showed higher ferritin levels (Z = 2.68; p = 0.007) and TSI (Z = 2.41; p = 0.016), but lower transferrin and TIBC (Z = 3.25; p = 0.001) than Child A patients. Transferrin and TIBC were directly related to albumin (ρ = 0.24; p = 0.026), whereas bilirubin showed direct relationships with iron (ρ = 0.25; p = 0.016), TSI (ρ = 0.39; p < 0.001) and ferritin (ρ = 0.36; p < 0.001). Both ferritin (ρ = -0.22; p = 0.04) and TSI (ρ = -0.25; p = 0.016) were related to platelet count. No relationships were observed between iron variables and Knodell index, but serum iron, serum transferrin, and TSI were directly related to Metavir-f score (ρ = 0.28; p = 0.009, ρ = 0.22; p = 0.044, and ρ = 0.22; p = 0.044, in this order). Conclusion: Alterations of iron related variables are relatively subtle in our series of 90 well compensated HCV patients. Serum ferritin was not related to liver fibrosis and increases only when alcoholism co-exists with HCV infection. 1. Introduction Iron overload is a common finding in chronic hepatitis C virus (HCV) infection [1], possibly in relation with impaired hepcidin se- cretion that accounts for increased iron absorption and excessive liver storage [2]. Increased liver iron would promote enhanced ferritin synthesis [3], and ferritin activates production of collagen and liver fibrogenesis [4]. This process might be more severe in alcoholics with HCV, since ethanol increases iron absorption, also mediated by down- regulation of hepcidin expression [5]. Therefore, serum ferritin could be a useful marker of ongoing fibrosis, a key feature in the progression of chronic HCV infection [6]. This chain of events has been challenged by several findings. Silva et al. (2005) found that iron overload in only 5 out of 96 HCV patients, and increased serum ferritin in 27% of pa- tients [7]. Similar results were reported by Haque et al. [8]. Fabris et al. found, among 69 HCV patients, relatively low serum ferritin values https://doi.org/10.1016/j.jtemb.2020.126542 Received 28 December 2019; Received in revised form 29 March 2020; Accepted 27 April 2020 ⁎ Corresponding author. E-mail addresses: candemartin1983@gmail.com (C. Martín-González), melrodgaspar@hotmail.com (M. Rodríguez-Gaspar), egonrey@ull.es (E. González-Reimers). 1 Senior author. Journal of Trace Elements in Medicine and Biology 61 (2020) 126542 0946-672X/ © 2020 Elsevier GmbH. All rights reserved. T