Role of transferrin receptor 2 in hepatic accumulation of iron in patients with chronic hepatitis C.
OBJECTIVE
Iron deposition in the liver is a common finding in patients with chronic hepatitis C (CH-C). The mechanism of this hepatic accumulation of iron is not completely understood. This study assessed if the protein expression of transferrin receptor 2 (TfR2) is upregulated in the liver of patients with CH-C and if TfR2 protein mediates iron accumulation during hepatitis C virus (HCV) infection.


METHODS
Liver specimens from patients with CH-C that underwent interferon (IFN) therapy (n=23) and from patients with CH-B (n=18) were evaluated. Hepatic expression of TfR2 protein was analyzed by immunohistochemistry. Total hepatic iron score (THIS) was evaluated by Prussian blue staining.


RESULTS
TfR2 protein was expressed in the cell membrane and cytosol of hepatocytes. Cytosol TfR2 protein was found to co-localize with Tf. THIS (P=0.0198) and hepatic TfR2 (P=0.0047) expression were significantly higher in CH-C than in CH-B. The change in THIS values (rho=0.580, P=0.0079) and the grade of histological activity (rho=0.444, P=0.0373) were significantly correlated with changes in TfR2 expression after IFN therapy.


CONCLUSIONS
The protein expression of TfR2 is significantly associated with iron deposition in the liver in patients with CH-C. HCV infection may affect the hepatic expression of TfR2, leading to iron accumulation in the liver.
Mifuji
Rumi
R
Department of Gastroenterology and Hepatology, Institute of Clinical Medicine and Biomedical Sciences, Mie University Graduate School of Medicine, Japan.
Kobayashi
Yoshinao
Y
Ma
Ning
N
Qiang
Qin Li
QL
Urawa
Naohito
N
Horiike
Shinichiro
S
Iwasa
Motoh
M
Kaito
Masahiko
M
Malavasi
Fabio
F
Adachi
Yukihiko
Y
D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D019694:Hepatitis B, Chronic / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007372:Interferons / Q000494:pharmacology / Q000627:therapeutic use; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011990:Receptors, Transferrin / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism
D000998:Antiviral Agents; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; D014168:Transferrin; D007372:Interferons; D007501:Iron