Serum ferritin levels are associated with a distinct phenotype of chronic hepatitis C poorly responding to pegylated interferon-alpha and ribavirin therapy.

Details

Serval ID
serval:BIB_6813444DD2EB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Serum ferritin levels are associated with a distinct phenotype of chronic hepatitis C poorly responding to pegylated interferon-alpha and ribavirin therapy.
Journal
Hepatology
Author(s)
Lange C.M., Kutalik Z., Morikawa K., Bibert S., Cerny A., Dollenmaier G., Dufour J.F., Gerlach T.J., Heim M.H., Malinverni R., Müllhaupt B., Negro F., Moradpour D., Bochud P.Y.
Working group(s)
Swiss Hepatitis C Cohort Study Group
Contributor(s)
Negro F., Hadengue A., Kaiser L., Rubbia-Brandt L., Moradpour D., Cellerai C., Rickenbach M., Cerny A., Martinetti G., Dufour JF., Gorgievski M., Spicher VM., Heim M., Hirsch H., Müllhaupt B., Helbling B., Regenass S., Malinverni R., Semela D., Dollenmaier G., Cathomas G.
ISSN
1527-3350 (Electronic)
ISSN-L
0270-9139
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
55
Number
4
Pages
1038-1047
Language
english
Notes
Publication types: Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Elevated serum ferritin levels may reflect a systemic inflammatory state as well as increased iron storage, both of which may contribute to an unfavorable outcome of chronic hepatitis C (CHC). We therefore performed a comprehensive analysis of the role of serum ferritin and its genetic determinants in the pathogenesis and treatment of CHC. To this end, serum ferritin levels at baseline of therapy with pegylated interferon-alpha and ribavirin or before biopsy were correlated with clinical and histological features of chronic hepatitis C virus (HCV) infection, including necroinflammatory activity (N = 970), fibrosis (N = 980), steatosis (N = 886), and response to treatment (N = 876). The association between high serum ferritin levels (> median) and the endpoints was assessed by logistic regression. Moreover, a candidate gene as well as a genome-wide association study of serum ferritin were performed. We found that serum ferritin ≥ the sex-specific median was one of the strongest pretreatment predictors of treatment failure (univariate P < 0.0001, odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.34-0.60). This association remained highly significant in a multivariate analysis (P = 0.0002, OR = 0.35, 95% CI = 0.20-0.61), with an OR comparable to that of interleukin (IL)28B genotype. When patients with the unfavorable IL28B genotypes were stratified according to high versus low ferritin levels, SVR rates differed by > 30% in both HCV genotype 1- and genotype 3-infected patients (P < 0.001). Serum ferritin levels were also independently associated with severe liver fibrosis (P < 0.0001, OR = 2.67, 95% CI = 1.68-4.25) and steatosis (P = 0.002, OR = 2.29, 95% CI = 1.35-3.91), but not with necroinflammatory activity (P = 0.3). Genetic variations had only a limited impact on serum ferritin levels. Conclusion: In patients with CHC, elevated serum ferritin levels are independently associated with advanced liver fibrosis, hepatic steatosis, and poor response to interferon-alpha-based therapy.
Keywords
Adolescent, Adult, Aged, Antiviral Agents/therapeutic use, Biological Markers/blood, Drug Therapy, Combination, Fatty Liver/epidemiology, Female, Ferritins/blood, Genotype, Hepacivirus/genetics, Hepatitis C, Chronic/blood, Hepatitis C, Chronic/complications, Humans, Incidence, Interferon-alpha/therapeutic use, Liver Cirrhosis/epidemiology, Male, Middle Aged, Phenotype, Polyethylene Glycols/therapeutic use, Recombinant Proteins/therapeutic use, Retrospective Studies, Ribavirin/therapeutic use, Risk Factors, Treatment Outcome, Young Adult
Pubmed
Web of science
Create date
05/05/2012 15:35
Last modification date
20/08/2019 14:23
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