Iron homeostasis is dysregulated,but the iron-hepcidin axis is functional,in chronic liver disease |
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| Institution: | 1. Innovative Clinical Trials, Department of Cardiology and Pneumology, University of Göttingen Medical School, Göttingen, Germany;2. Applied Cachexia Research, Department of Cardiology, Charité Medical School, Berlin, Germany;1. Department of Pharmacy, Second Artillery General Hospital Beijing China;2. Department of Oncology, 304 Hospital, Chinese PLA General Hospital Beijing China;3. Department of Pharmacology, Beijing Institute of Microbiology and Epidemiology Beijing China;1. Gastroenterology Service, Donostia University Hospital, Donostia, Spain;2. Clinical Epidemiology Unit, CASPe, CIBER-ESP, Donostia University Hospital, Donostia, Spain;3. Clinical Epidemiology Unit, CASPe, CIBER-ESP, Donostia University Hospital, Donostia, Spain;4. Immunology Service, Donostia University Hospital, Donostia, Spain;5. Radiology Service, Osatek Donostia, Donostia, Spain;1. Department of Surgery, University of Missouri, Columbia, MO, USA;2. Division of Surgical Oncology, Columbia, MO, USA;3. Ellis Fischel Cancer Center, Columbia, MO, USA;4. Department of Otolaryngology—Head and Neck Surgery, University of Missouri, Columbia, MO, USA |
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| Abstract: | BackgroundPerturbations in iron homeostasis have been reported to be associated with irreversible liver injury in chronic liver disease (CLD). However, it is not clear whether liver dysfunction per se underlies such dysregulation or whether other factors also contribute to it. This study attempted to examine the issues involved.MethodsPatients diagnosed to have chronic liver disease (n = 63), who underwent a medically-indicated upper gastrointestinal endoscopy, were the subjects of this study. Patients with dyspepsia, who underwent such a procedure, and were found to have no endoscopic abnormalities, were used as control subjects (n = 49). Duodenal mucosal samples were obtained to study mRNA and protein levels of duodenal proteins involved in iron absorption. A blood sample was also obtained for estimation of hematological, iron-related, inflammatory and liver function-related parameters.ResultsPatients with CLD had impaired liver function, anemia of inflammation and lower serum levels of hepcidin than control subjects. Gene (mRNA) expression levels of duodenal ferroportin and duodenal cytochrome b (proteins involved in iron absorption) were decreased, while that of divalent metal transporter–1 (DMT-1) was unchanged. Protein expression of DMT-1 was, however, decreased while that of ferroportin was unchanged. In the CLD group, serum hepcidin was predicted independently by serum ferritin and hemoglobin, but not by C-reactive protein (a marker of inflammation). CLD patients with serum ferritin greater than 300 μg/dL had significantly greater liver dysfunction (as indicated by significantly higher serum concentrations of bilirubin, AST and ALT, and MELD scores), higher serum concentrations of CRP and hepcidin, and higher ferroportin protein expression, than those with serum ferritin ≤ 300 μg/dL.ConclusionsIn patients with CLD, anemia of inflammation and low serum hepcidin levels were found to paradoxically co-exist. Expression of duodenal proteins involved in iron absorption were either decreased or unaltered in these patients. The hepcidin response to higher body iron levels and/or inflammation appeared to be functional in these patients, despite the presence of liver disease. |
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| Keywords: | Iron absorption DMT-1 Ferroportin Chronic liver disease Hepcidin |
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