title: Hepcidin expression in the liver: relatively low level in patients with chronic hepatitis C.
abstract: Patients with chronic hepatitis C frequently have serum and hepatic iron overload, but the mechanism is unknown. Recently identified hepcidin, exclusively synthesized in the liver, is thought to be a key regulator for iron homeostasis and is induced by infection and inflammation. This study was conducted to determine the hepatic hepcidin expression levels in patients with various liver diseases. We investigated hepcidin mRNA levels of liver samples by real-time detection-polymerase chain reaction; 56 were hepatitis C virus (HCV) positive, 34 were hepatitis B virus (HBV) positive, and 42 were negative for HCV and HBV (3 cases of auto-immune hepatitis, 7 alcoholic liver disease, 13 primary biliary cirrhosis, 9 nonalcoholic fatty liver disease, and 10 normal liver). We analyzed the relation of hepcidin to clinical, hematological, histological, and etiological findings. Hepcidin expression levels were strongly correlated with serum ferritin (P < 0.0001) and the degree of iron deposit in liver tissues (P < 0.0001). Hepcidin was also correlated with hematological parameters (vs. hemoglobin, P = 0.0073; vs. serum iron, P = 0.0012; vs. transferrin saturation, P < 0.0001) and transaminase levels (P = 0.0013). The hepcidin-to-ferritin ratio was significantly lower in HCV(+) patients than in HBV(+) patients (P = 0.0129) or control subjects (P = 0.0080). In conclusion, hepcidin expression levels in chronic liver diseases were strongly correlated with either the serum ferritin concentration or degree of iron deposits in the liver. When adjusted by either serum ferritin values or hepatic iron scores, hepcidin indices were significantly lower in HCV(+) patients than in HBV(+) patients, suggesting that hepcidin may play a pivotal role in the pathogenesis of iron overload in patients with chronic hepatitis C.
authors.affiliation: Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Science, Institute of Medical Science, Mie University Graduate School of Medicine, Mie, Japan. nfujita@clin.medic.mie-u.ac.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Fujita
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Sugimoto
authors.forename: Masaki
authors.initials: M
authors.lastname: Takeo
authors.forename: Naohito
authors.initials: N
authors.lastname: Urawa
authors.forename: Rumi
authors.initials: R
authors.lastname: Mifuji
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Motoh
authors.initials: M
authors.lastname: Iwasa
authors.forename: Shozo
authors.initials: S
authors.lastname: Watanabe
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Adachi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kaito
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000097:blood; D005260:Female; D005293:Ferritins / Q000097:blood; D006454:Hemoglobins / Q000032:analysis; D016174:Hepacivirus / Q000235:genetics; D006509:Hepatitis B / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000378:metabolism*; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000097:blood; D019190:Iron Overload / Q000209:etiology; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008107:Liver Diseases / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014168:Transferrin / Q000032:analysis
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D006454:Hemoglobins; D064451:Hepcidins; D012333:RNA, Messenger; D012367:RNA, Viral; D014168:Transferrin; D005293:Ferritins; D007501:Iron; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase