PEG-IFNα/RBV Combination Therapy for Chronic Hepatitis C Patients Increases Serum Ferritin Level while It Improves Sustained Viral Response Rate

Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan.
Intervirology (Impact Factor: 1.68). 01/2010; 53(1):60-5. DOI: 10.1159/000252786
Source: PubMed


We investigated the significance of serum ferritin levels in pegylated interferon (PEG-IFN) and ribavirin (RBV) combination therapy for chronic hepatitis C (CHC) and examined its correlation with serum alanine aminotransferase (ALT) levels during therapy and response to the therapy.
A total of 175 patients with CHC received the combination therapy. Correlations between serum ferritin levels and serum ALT levels at 12 and 24 weeks of therapy were examined. Differences in serum ferritin levels during therapy between patients with sustained viral response (SVR) and non-SVR were also examined.
Only 24 (13.7%) and 20 (11.4%) patients showed elevated serum ALT levels (> or = 70 IU/l) at 12 and 24 weeks of therapy, respectively. There was no correlation between serum ferritin levels and ALT levels. Ninety-five (54.3%) of 175 patients achieved SVR. Serum ferritin levels increased dramatically in both SVR and non-SVR groups after starting the therapy and were significantly higher in the SVR group throughout the therapy.
Serum ferritin level increases during PEG-IFN and RBV combination therapy; however, it did not correlate with either serum ALT level or the total dose of RBV. Higher serum ferritin levels during combination therapy appear to be associated with favorable therapeutic response.

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    • "In the current study the correlation between the degree of hemolysis and on-treatment serum ferritin levels was insignificant. Other investigators reported similar results [Ferrara et al., 2009; Ladero et al., 2009; Yada et al., 2010]. However, hemolysis may have a minor contribution to serum ferritin levels only during the first month of antiviral treatment [Ferrara et al., 2009]. "
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    ABSTRACT: An increase in serum ferritin levels during combined interferon-ribavirin treatment in chronic patients infected with hepatitis C virus (HCV) can occur. A study was conducted to determine whether observing the kinetics of serum ferritin levels during antiviral therapy, may assist in predicting the rate of sustained virological response. The kinetics of serum ferritin levels during antiviral therapy in treatment-naive, adherent patients with chronic HCV who had early virological response were characterized. Thirteen patients achieved sustained virological response (group 1) while eight patients did not (group 2). Pre-treatment serum ferritin levels were higher in group 2 patients. During antiviral therapy, serum ferritin levels increased in both groups. On treatment, the median increase (compared to baseline) and the calculated rate of the increase in serum ferritin levels was higher in group 1 patients (874% vs. 272%, P < 0.05, 63%/week vs. 13%/week, P = 0.024, respectively). Red blood cell lysis did not contribute to the increase in serum ferritin level. Post-treatment (1st month) serum ferritin levels in group 1 patients were lower than in group 2 patients. In addition, the degree of decline in the 1st month serum ferritin levels (from peak levels) in group 1 patients was higher (76% vs. 49%, P = 0.039). Measuring serum ferritin levels during antiviral therapy in HCV patients who had an early virological response may assist in predicting sustained virological response.
    Journal of Medical Virology 07/2011; 83(7):1262-8. DOI:10.1002/jmv.22093 · 2.35 Impact Factor

  • Intervirology 01/2010; 53(1):5-9. DOI:10.1159/000252777 · 1.68 Impact Factor
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    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.
    Hepatology 04/2012; 55(4):1038-47. DOI:10.1002/hep.24787 · 11.06 Impact Factor
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