title: Low hepcidin triggers hepatic iron accumulation in patients with hepatitis C.
abstract: Persistent hepatitis C virus (HCV) infection is a major cause of chronic liver disease including fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Chronic hepatitis C (CHC) is also a problem in patients with chronic kidney disease (CKD), particularly in those on haemodialysis. Excessive iron in the liver of CHC patients contributes to hepatic fibrosis, cirrhosis and finally HCC, while iron depletion is beneficial. In CHC patients without CKD, in HCV-infected experimental animals and in cell culture studies, serum hepcidin levels and/or cellular hepcidin expression are low and directly suppressed by HCV, radical oxygen species, growth factors and/or transcription factors. In contrast, antiviral therapy (e.g. with pegylated interferon-alpha combined with ribavirin) raises hepcidin levels and reduces iron overload in patients with CHC. Hepcidin directly inhibits HCV replication mediated by STAT3 activation. HCV circumvents hepatic innate antiviral defence by lowering hepcidin. If hepcidin is also low in CKD patients with CHC, iron supplementation should be avoided even in CKD patients with CHC treated with erythropoiesis-stimulating agents.
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Walter H
authors.initials: WH
authors.lastname: Hörl
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Alice
authors.initials: A
authors.lastname: Schmidt
mesh_terms: D000328:Adult; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use; D004815:Epidermal Growth Factor / Q000502:physiology; D005260:Female; D016174:Hepacivirus / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D017228:Hepatocyte Growth Factor / Q000502:physiology; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D018962:Phlebotomy; D051436:Renal Insufficiency, Chronic / Q000097:blood; D012254:Ribavirin / Q000627:therapeutic use; D014779:Virus Replication / Q000502:physiology
chemical_list: D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents; D064451:Hepcidins; D016898:Interferon-alpha; D012254:Ribavirin; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D007501:Iron
keywords: hepatitis C; hepcidin; iron; liver