Hepcidin as a predictor of treatment response in chronic hepatitis C infection

Authors

  • Pavel Strnad M.D.,

    1. Interdisciplinary Center for Clinical Research, IZKF and Department of Internal Medicine III, Aachen University Hospital, Aachen, Germany
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  • Renwar Nuraldeen M.D.,

    1. Interdisciplinary Center for Clinical Research, IZKF and Department of Internal Medicine III, Aachen University Hospital, Aachen, Germany
    2. Department of Internal Medicine I, Ulm University Hospital, Ulm, Germany
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  • Janett Fischer Ph.D.,

    1. Department of Hepatology, Clinic of Gastroenterology and Rheumatology, Leipzig University Hospital, Leipzig, Germany
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  • Thomas Berg M.D.,

    1. Department of Hepatology, Clinic of Gastroenterology and Rheumatology, Leipzig University Hospital, Leipzig, Germany
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  • Christian Trautwein M.D.

    1. Interdisciplinary Center for Clinical Research, IZKF and Department of Internal Medicine III, Aachen University Hospital, Aachen, Germany
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  • Potential conflict of interest: Nothing to report.

  • This work was supported by grants from the Interdisciplinary Center for Clinical Research within the Faculty of Medicine at RWTH Aachen University and the German Research Foundation (SFB TRR57 to Pavel Strnad).

To the Editor:

With interest, we read the article by Ryan et al.,[1] who evaluated the importance of iron metabolism during the treatment of chronic hepatitis C infection. In particular, their observations suggest that pegylated interferon α, an integral part of the current treatment of chronic hepatitis C virus infection, leads to hypoferremia via the induction of hepcidin, and the extent of hypoferremia correlates with the reduction of the viral load.

Hepcidin plays an important role in both iron metabolism and innate immunity.[2] Therefore, we analyzed its predictive ability during the treatment of chronic hepatitis C. Seventy-four patients with chronic hepatitis C (all genotype I) undergoing dual therapy with pegylated interferon α and ribavirin were included. Hepcidin levels were evaluated at the baseline, at weeks 1, 4, 12, 24 and 6 months after the end of treatment with a commercially available enzyme-linked immunosorbent assay kit (EIA-5258, DRG Instruments, Marburg, Germany; Fig. 1). The study protocol received a priori approval by the appropriate institutional review committee. At the baseline, weak correlations between hepcidin levels and serum ferritin (r = 0.27), body mass index (r = 0.29), and hemoglobin levels (r = 0.32) were observed. On the other hand, we detected a negative relationship between hepcidin and alanine aminotransferase (r = −0.25) and platelet levels (r = −0.25). Male patients displayed significantly higher hepcidin levels. At week 1 of treatment, a significant increase (P < 0.0001) in serum hepcidin levels was found. However, the levels largely returned to the baseline by week 4 and remained stable subsequently (Fig. 1). Neither baseline hepcidin levels nor the increase at week 1 or 4 correlated with the end-of-treatment response or the achievement of a sustained virological response. Although steatosis has been previously shown to be a negative predictive marker for viral clearance,[3] steatotic subjects demonstrated a significantly higher rise in hepcidin levels at week 1 versus the baseline (P < 0.001). Finally, 50 patients who achieved a sustained virological response displayed significantly higher hepcidin values 6 months after the end of treatment in comparison with nonresponders (7.3 ± 0.7 versus 4.1 ± 0.5 ng/mL, P < 0.001), and this is in line with previous reports.[4]

Figure 1.

Impact of dual antiviral therapy on serum hepcidin levels. The results are shown as averages and standard errors. *P < 0.01; **P < 0.001; ***P < 0.0001. Abbreviations: 6m, 6 months after the end of treatment; W1, therapy week 1; W4, therapy week 4; W12, therapy week 12; W24, therapy week 24.

In conclusion, dual therapy leads to striking up-regulation of hepcidin levels, which likely contributes to the development of anemia in treated subjects. Further studies are needed to determine whether antiviral drugs themselves or events occurring at the same time (e.g., an increase in serum iron levels due to hemolysis) are responsible for the observed hepcidin rise. Anyway, hepcidin serum levels and changes during therapy are not predictive markers for the antiviral treatment response.

  • Pavel Strnad, M.D.1

  • Renwar Nuraldeen, M.D.1,2

  • Janett Fischer, Ph.D.3

  • Thomas Berg, M.D.3

  • Christian Trautwein, M.D.1

  • 1Interdisciplinary Center for Clinical Research

  • IZKF and Department of Internal Medicine III

  • Aachen University Hospital

  • Pauwelsstraße 30, D-52074,

  • Aachen, Germany

  • 2Department of Internal Medicine I

  • Ulm University Hospital

  • Ulm, Germany

  • 3Department of Hepatology

  • Clinic of Gastroenterology and Rheumatology

  • Leipzig University Hospital

  • Leipzig, Germany

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