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

Hepatology. 2011 Nov 16. doi: 10.1002/hep.24787. [Epub ahead of print]

Lange CM, Kutalik Z, Morikawa K, Bibert S, Cerny A, Dollenmaier G, Dufour JF, Gerlach TJ, Heim MH, Malinverni R, Müllhaupt B, Negro F, Moradpour D, Bochud PY; the Swiss Hepatitis C Cohort Study Group.

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Division of Gastroenterology and Hepatology, University Hospital Lausanne, CH-1011 Lausanne, Switzerland; Medizinische Klinik 1, Klinikum der J. W. Goethe-Universität Frankfurt a.M., D-60590 Frankfurt a.M., Germany. Christian.Lange@chuv.ch.

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. We therefore performed a comprehensive analysis of the role of serum ferritin and their genetic determinants in the pathogenesis and treatment of chronic hepatitis C. To this end, serum ferritin levels at baseline of therapy with pegylated interferon-α and ribavirin or before biopsy were correlated with clinical and histological features of chronic 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 pre-treatment predictors of treatment failure (univariate P<0.0001, OR=0.45, 95% 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 odds ratio comparable to that of IL28B genotype. When patients with the unfavorable IL28B genotypes were stratified according to high vs. low ferritin levels, SVR rates differed by >30% in both HCV genotype 1- and 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 chronic hepatitis C, elevated serum ferritin levels are independently associated with advanced liver fibrosis, hepatic steatosis, and poor response to interferon-α-based therapy. (HEPATOLOGY 2011.).

Copyright © 2011 American Association for the Study of Liver Diseases.

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