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

Hepatology, 05/02/2012

In patients with chronic hepatitis C (CHC), elevated serum ferritin levels are independently associated with advanced liver fibrosis, hepatic steatosis, and poor response to interferon–alpha–based therapy.

Methods

  • The authors 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.

Results

  • They 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.

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