Prognostic Value of Serum Iron, Ferritin, and Transferrin in Chronic Alcoholic Liver Disease
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Ethanol increases iron absorption. Therefore, increased amount of iron reaches the liver, and exerts pro-oxidant effects and stimulates ferritin synthesis and hepatic stellate cell activation, promoting fibrosis and inflammation. These mechanisms would theoretically support a role of ferritin as a marker of the transition to liver cirrhosis, and, consequently, as a prognostic factor, but there is controversy regarding its behavior in alcoholics. We analyzed among 238 severe alcoholics the prognostic value of iron, ferritin, transferrin, transferrin saturation index (TSI) and total iron binding capacity (TIBC), and the relationships of these variables with liver function, proinflammatory markers (C-reactive protein (CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor α), and the presence of cirrhosis. Patients showed higher serum ferritin (Z = 2.50, p = 0.031) but lower transferrin (t(264) = 4.81, p < 0.001), TIBC (t(262) = 4.44, p < 0.001), and iron (Z = 3.19, p = 0.001) values compared with 32 age- and sex-matched controls. Ferritin was related to inflammatory cytokines such as IL-8 (ρ = 0.18, p = 0.012) and to IL-6 (ρ = 0.16, p = 0.016), but not to liver function. On the contrary, cirrhotics showed lower transferrin (t(234) = 4.77, p < 0.001) and TIBC (t(232) = 4.67, p < 0.001), but higher TSI (Z = 3.35, p < 0.001) than non-cirrhotics. Transferrin, TSI, and TIBC were related to liver function impairment (marked differences among the Child’s groups regarding transferrin (KW (2) = 22.83, p < 0.001), TSI (KW (2) = 15.81, p < 0.001), and TIBC (KW (2) = 21.38, p < 0.001) but only weakly to inflammation (inverse relationships between IL-6 and total iron (ρ = − 0.16, p = 0.017), TIBC (ρ = − 0.20, p = 0.002), and transferrin (ρ = − 0.20, p = 0.003). In accordance, albumin, IL-6, alcohol quitting, and TSI, in this order, were independently related to mortality, but not ferritin or iron.
KeywordsCirrhosis Alcoholism Iron Ferritin Transferrin Proinflammatory cytokines
Compliance with Ethical Standards
The study protocol was approved by the local ethical committee of our Hospital (CHUC_2019_83) and conforms to the ethical guidelines of the 1975 Declaration of Helsinki. All the patients gave their written informed consent.
Conflict of Interest
The authors declare that they have no conflict of interest.
- 8.Harrison-Findik DD, Schafer D, Klein E, Timchenko NA, Kulaksiz H, Clemens D, Fein E, Andriopoulos B, Pantopoulos K, Gollan J (2006) Alcohol metabolism-mediated oxidative stress down-regulates hepcidin transcription and leads to increased duodenal iron transporter expression. J Biol Chem 281:22974–22982CrossRefPubMedGoogle Scholar
- 14.Ruddell RG, Hoang-Le D, Barwood JM, Rutherford PS, Piva TJ, Watters DJ, Santambrogio P, Arosio P, Ramm GA (2009) Ferritin functions as a proinflammatory cytokine via iron-independent protein kinase C zeta/nuclear factor kappaB-regulated signaling in rat hepatic stellate cells. Hepatology 49:887–900. https://doi.org/10.1002/hep.22716 CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Weismüller TJ, Kirchner GI, Scherer MN, Negm AA, Schnitzbauer AA, Lehner F, Klempnauer J, Schlitt HJ, Manns MP, Strassburg CP (2011) Serum ferritin concentration and transferrin saturation before liver transplantation predict decreased long-term recipient survival. Hepatology 54:2114–2124. https://doi.org/10.1002/hep.24635 CrossRefPubMedGoogle Scholar
- 19.Bruns T, Nuraldeen R, Mai M, Stengel S, Zimmermann HW, Yagmur E, Trautwein C, Stallmach A, Strnad P (2017) Low serum transferrin correlates with acute-on-chronic organ failure and indicates short-term mortality in decompensated cirrhosis. Liver Int 37:232–241. https://doi.org/10.1111/liv.13211 CrossRefPubMedGoogle Scholar
- 20.Al -Freah MA, Kriese S, Foxton MR, Quaglia A, Bomford A, Heaton ND, O’Grady JG, Agarwal K, Wendon JA, Heneghan MA (2013) The association of pretransplant ferritin level with waiting list and post-transplant survival. Does ferritin actually predict outcome? Transpl Int 26:1070–1079. https://doi.org/10.1111/tri.12164 CrossRefGoogle Scholar