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Hepcidin/ferroportin expression levels involve efficacy of pegylated-interferon plus ribavirin in hepatitis C virus-infected liver.
- Source :
-
World journal of gastroenterology [World J Gastroenterol] 2015 Mar 21; Vol. 21 (11), pp. 3291-9. - Publication Year :
- 2015
-
Abstract
- Aim: To investigate the relationship between the iron-metabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C patients.<br />Methods: The hepatic expression profile of iron-metabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated. A hundred patients with chronic hepatitis C (genotype1b, n = 50; genotype 2, n = 50) were enrolled and retrospectively analyzed. Liver biopsy samples were subjected to quantitative polymerase chain reaction for iron-metabolism-related genes and protein expression (Western blotting analysis) for ferroportin. As a control, normal liver tissue was obtained from 18 living donors of liver transplantation. Serum hepcidin level was measured by sensitive liquid chromatography/electrospray ionization tandem mass spectrometry.<br />Results: Iron overload is associated with liver damage by increasing oxidative stress and hepatitis C virus (HCV) is reported to induce iron accumulation in hepatocytes in vivo. Conversely, iron administration suppresses HCV replication in vitro. Therefore, the association between HCV infection and iron metabolism remains unclear. Compared with controls, patients had significantly higher gene expression for transferrin, iron-regulatory proteins 1 and 2, divalent metal transporter 1, and ferroportin, but similar for transferrin receptors 1 and 2, and hepcidin. When the expression profiles were compared between sustained virological response (SVR) and non-SVR patients, the former showed significantly lower transcription and protein expression of hepcidin and ferroportin. Expression of hepcidin-regulating genes, BMPR1, BMPR2, and hemojuvelin, was significantly increased, whereas BMP2 was decreased in HCV-infected liver. BMPR2 and hemojuvelin expression was significantly lower in the SVR than non-SVR group. HCV infection affects the expression of iron-metabolism-related genes, leading to iron accumulation in hepatocytes.<br />Conclusion: Decreased expression of hepcidin and ferroportin in SVR patients indicates the importance of hepatocytic iron retention for viral response during pegylated-interferon plus ribavirin treatment.
- Subjects :
- Blotting, Western
Cation Transport Proteins genetics
Chromatography, Liquid
Drug Therapy, Combination
Female
Gene Expression Profiling methods
Gene Expression Regulation
Hepatitis C, Chronic diagnosis
Hepatitis C, Chronic genetics
Hepatitis C, Chronic metabolism
Hepcidins genetics
Humans
Interferon alpha-2
Liver metabolism
Liver virology
Male
Middle Aged
Polymerase Chain Reaction
Recombinant Proteins therapeutic use
Retrospective Studies
Spectrometry, Mass, Electrospray Ionization
Tandem Mass Spectrometry
Time Factors
Treatment Outcome
Antiviral Agents therapeutic use
Cation Transport Proteins metabolism
Hepatitis C, Chronic drug therapy
Hepcidins metabolism
Interferon-alpha therapeutic use
Liver drug effects
Polyethylene Glycols therapeutic use
Ribavirin therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 2219-2840
- Volume :
- 21
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- World journal of gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 25805936
- Full Text :
- https://doi.org/10.3748/wjg.v21.i11.3291