Elevated serum transaminase activities were associated with increased serum levels of iron regulatory hormone hepcidin and hyperferritinemia risk

Abstract

Iron imbalance is a feature of liver damage. However, the biological correlation of serum hepcidin, a key regulator of iron homeostasis, with liver malfunction is undefined. To this end, we piloted the Chinese population studies to address whether hepcidin is linked to liver functionality. The serum hepcidin, ferritin, alanine transaminase, aspartate transaminase, gamma-glutamyltransferase and bilirubin were examined in two independent Chinese cohorts consisted of 3455 individuals. After adjustment for sex, age, body mass index, smoking habits, drinking categories and diabetic status, a positive association between hepcidin and alanine transaminase (ALT) (beta = 0.18 ± 0.01, P < 0.0001) was discovered using linear regression in a cohort consisting of 1813 individuals. This association was then validated in the second independent cohort of 1642 individuals (beta = 0.08 ± 0.02, P < 0.0001). Furthermore, consistent with cohort study, by applying both CCl4 and lipopolysaccharide induced mouse liver injury models, at least 2-fold elevations in hepcidin expression, serum ALT and inflammatory cytokine IL-6 were discovered during the initiation stage of liver injury. Our findings suggest that increased serum hepcidin may reflect a protective response to the iron status and elevated serum cytokines during liver injury. Additional studies are warranted to validate these findings and test their potential clinical relevance in patients.

Effect of Serum Ferritin on the Prognosis of Patients with Sepsis: Data from the MIMIC-IV Database

“…The marked reductions in circulating iron mediated by hepcidin can effectively increase the expression of ferritin. What is more, the damage to hepatocytes may result in the release of ferritin into circulation, which is the principal site for the storage of ferritin [ 34 , 35 ]. Hepatocyte injury also leads to the abnormal synthesis and secretion of hepcidin, which also contributes to the abnormal expression of ferritin [ 34 ].…”

“…What is more, the damage to hepatocytes may result in the release of ferritin into circulation, which is the principal site for the storage of ferritin [ 34 , 35 ]. Hepatocyte injury also leads to the abnormal synthesis and secretion of hepcidin, which also contributes to the abnormal expression of ferritin [ 34 ]. Ferritin is regarded as a protective factor.…”

Inflammatory Biomarkers of Cardiometabolic Risk in Obese Egyptian Type 2 Diabetics

“…There was a statistically significant increase in the same markers when comparing diabetic groups to the non-diabetic group; this was in agreement with previous studies. Rajeev G. et al [ 51 ] and An P. et al [ 52 ] stated that inflammation as measured by serum inflammatory markers has been shown to be increased in people with diabetes. There was a significant correlation between hs-CRP, IL-6 and TNF-α with measures of obesity such as BMI and WC.…”

Hepatic transferrin plays a role in systemic iron homeostasis and liver ferroptosis

“…The following were performed as previously described: PHZinduced hemolysis; iron dextran injection; HID treatment; Fer-1 treatment; carbon tetrachloride (CCl 4 )-induced fibrosis murine model; flow cytometry analysis; serum iron, tissue non-heme iron, and serum NTBI testing; Perls Prussian blue, ALT, Sirius Red, Masson's trichrome, and 4-hydroxynonenal (4-HNE) staining; analysis of malondialdehyde (MDA), thiol, and superoxide dismutase (SOD) enzyme activity; reverse transcription polymerase chain reaction (RT-PCR); western blot analysis; IHC; and measurement of serum Trf and serum erythropoietin (Epo). 15,[19][20][21][22][23][24][25][26] Detailed information about these methods is available in the supplemental Methods.…”