Serum ferritin as a predictor of treatment outcome in patients with chronic hepatitis C

Francesca Ferrara, Paolo Ventura, Alberto Vegetti, Maria Guido, Gianluca Abbati, Elena Corradini, Giovanna Fattovich, Carlo Ferrari, Mara Tagliazucchi, Anna Carbonieri, Alessandra Orlandini, Stefano Fagiuoli, Sara Boninsegna, Eliseo Minola, Giovanna Rizzo, Fabio Belussi, Martina Felder, Marco Massari, Gabriele Pozzato, Stefania BonettoPierangelo Rovere, Carla Sardini, Athos Borghi, Maria Luisa Zeneroli, Pierluigi Toniutto, Elisabetta Rossi, Antonello Pietrangelo

Research output: Contribution to journalArticle

Abstract

OBJECTIVES: Antiviral treatment in chronic hepatitis C (CHC) involves ribavirin, a hemolytic agent. We planned a prospective study to evaluate whether drug-induced iron perturbation is clinically relevant as it relates to therapeutic outcome. METHODS: Iron variables were sequentially assessed in 206 CHC patients undergoing antiviral therapy and were correlated with pretreatment iron status and histology, hemolysis, and therapeutic outcome. RESULTS: At week 1 of therapy, serum iron (SI), transferrin saturation (TS), and serum ferritin (SF) increased markedly in all patients. All iron parameters correlated with hemolysis up to week 4; this correlation was lost for SF at later time points. SF rise during treatment was inversely related to baseline SF and iron deposits in hepatic mesenchymal/Kupffer cells. Both baseline SF and mesenchymal iron significantly correlated with fibrosis at multivariate analysis (P=0.015 and 0.008, respectively). Interestingly, baseline SF, despite good specificity (89%), had low sensitivity in predicting siderosis (25%). During therapy, SI, TS, and hemolysis parameters did not correlate with sustained virological response (SVR), whereas SF rise became an independent predictor of therapeutic response: a 2.5-fold increase of SF at week 12 associated with higher likelihood of SVR (odds ratio 1.91, P=0.032). Accordingly, lack of mesenchymal iron deposits at the baseline biopsy correlated with SVR (odds ratio 3.02, P=0.043). CONCLUSIONS: In CHC, SF is a useful marker for assessing disease duration and progression before starting treatment and for predicting therapeutic response while on therapy. SF rise during antiviral therapy is largely independent of hemolysis and likely indicates activation of macrophages in response to antivirals.

Original languageEnglish
Pages (from-to)605-616
Number of pages12
JournalAmerican Journal of Gastroenterology
Volume104
Issue number3
DOIs
Publication statusPublished - Mar 2009

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Chronic Hepatitis C
Ferritins
Iron
Serum
Hemolysis
Antiviral Agents
Therapeutics
Transferrin
Hemolytic Agents
Odds Ratio
Siderosis
Kupffer Cells
Macrophage Activation
Ribavirin
Disease Progression
Histology
Fibrosis
Multivariate Analysis
Prospective Studies
Biopsy

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Ferrara, F., Ventura, P., Vegetti, A., Guido, M., Abbati, G., Corradini, E., ... Pietrangelo, A. (2009). Serum ferritin as a predictor of treatment outcome in patients with chronic hepatitis C. American Journal of Gastroenterology, 104(3), 605-616. https://doi.org/10.1038/ajg.2008.126

Serum ferritin as a predictor of treatment outcome in patients with chronic hepatitis C. / Ferrara, Francesca; Ventura, Paolo; Vegetti, Alberto; Guido, Maria; Abbati, Gianluca; Corradini, Elena; Fattovich, Giovanna; Ferrari, Carlo; Tagliazucchi, Mara; Carbonieri, Anna; Orlandini, Alessandra; Fagiuoli, Stefano; Boninsegna, Sara; Minola, Eliseo; Rizzo, Giovanna; Belussi, Fabio; Felder, Martina; Massari, Marco; Pozzato, Gabriele; Bonetto, Stefania; Rovere, Pierangelo; Sardini, Carla; Borghi, Athos; Zeneroli, Maria Luisa; Toniutto, Pierluigi; Rossi, Elisabetta; Pietrangelo, Antonello.

In: American Journal of Gastroenterology, Vol. 104, No. 3, 03.2009, p. 605-616.

Research output: Contribution to journalArticle

Ferrara, F, Ventura, P, Vegetti, A, Guido, M, Abbati, G, Corradini, E, Fattovich, G, Ferrari, C, Tagliazucchi, M, Carbonieri, A, Orlandini, A, Fagiuoli, S, Boninsegna, S, Minola, E, Rizzo, G, Belussi, F, Felder, M, Massari, M, Pozzato, G, Bonetto, S, Rovere, P, Sardini, C, Borghi, A, Zeneroli, ML, Toniutto, P, Rossi, E & Pietrangelo, A 2009, 'Serum ferritin as a predictor of treatment outcome in patients with chronic hepatitis C', American Journal of Gastroenterology, vol. 104, no. 3, pp. 605-616. https://doi.org/10.1038/ajg.2008.126
Ferrara, Francesca ; Ventura, Paolo ; Vegetti, Alberto ; Guido, Maria ; Abbati, Gianluca ; Corradini, Elena ; Fattovich, Giovanna ; Ferrari, Carlo ; Tagliazucchi, Mara ; Carbonieri, Anna ; Orlandini, Alessandra ; Fagiuoli, Stefano ; Boninsegna, Sara ; Minola, Eliseo ; Rizzo, Giovanna ; Belussi, Fabio ; Felder, Martina ; Massari, Marco ; Pozzato, Gabriele ; Bonetto, Stefania ; Rovere, Pierangelo ; Sardini, Carla ; Borghi, Athos ; Zeneroli, Maria Luisa ; Toniutto, Pierluigi ; Rossi, Elisabetta ; Pietrangelo, Antonello. / Serum ferritin as a predictor of treatment outcome in patients with chronic hepatitis C. In: American Journal of Gastroenterology. 2009 ; Vol. 104, No. 3. pp. 605-616.
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abstract = "OBJECTIVES: Antiviral treatment in chronic hepatitis C (CHC) involves ribavirin, a hemolytic agent. We planned a prospective study to evaluate whether drug-induced iron perturbation is clinically relevant as it relates to therapeutic outcome. METHODS: Iron variables were sequentially assessed in 206 CHC patients undergoing antiviral therapy and were correlated with pretreatment iron status and histology, hemolysis, and therapeutic outcome. RESULTS: At week 1 of therapy, serum iron (SI), transferrin saturation (TS), and serum ferritin (SF) increased markedly in all patients. All iron parameters correlated with hemolysis up to week 4; this correlation was lost for SF at later time points. SF rise during treatment was inversely related to baseline SF and iron deposits in hepatic mesenchymal/Kupffer cells. Both baseline SF and mesenchymal iron significantly correlated with fibrosis at multivariate analysis (P=0.015 and 0.008, respectively). Interestingly, baseline SF, despite good specificity (89{\%}), had low sensitivity in predicting siderosis (25{\%}). During therapy, SI, TS, and hemolysis parameters did not correlate with sustained virological response (SVR), whereas SF rise became an independent predictor of therapeutic response: a 2.5-fold increase of SF at week 12 associated with higher likelihood of SVR (odds ratio 1.91, P=0.032). Accordingly, lack of mesenchymal iron deposits at the baseline biopsy correlated with SVR (odds ratio 3.02, P=0.043). CONCLUSIONS: In CHC, SF is a useful marker for assessing disease duration and progression before starting treatment and for predicting therapeutic response while on therapy. SF rise during antiviral therapy is largely independent of hemolysis and likely indicates activation of macrophages in response to antivirals.",
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T1 - Serum ferritin as a predictor of treatment outcome in patients with chronic hepatitis C

AU - Ferrara, Francesca

AU - Ventura, Paolo

AU - Vegetti, Alberto

AU - Guido, Maria

AU - Abbati, Gianluca

AU - Corradini, Elena

AU - Fattovich, Giovanna

AU - Ferrari, Carlo

AU - Tagliazucchi, Mara

AU - Carbonieri, Anna

AU - Orlandini, Alessandra

AU - Fagiuoli, Stefano

AU - Boninsegna, Sara

AU - Minola, Eliseo

AU - Rizzo, Giovanna

AU - Belussi, Fabio

AU - Felder, Martina

AU - Massari, Marco

AU - Pozzato, Gabriele

AU - Bonetto, Stefania

AU - Rovere, Pierangelo

AU - Sardini, Carla

AU - Borghi, Athos

AU - Zeneroli, Maria Luisa

AU - Toniutto, Pierluigi

AU - Rossi, Elisabetta

AU - Pietrangelo, Antonello

PY - 2009/3

Y1 - 2009/3

N2 - OBJECTIVES: Antiviral treatment in chronic hepatitis C (CHC) involves ribavirin, a hemolytic agent. We planned a prospective study to evaluate whether drug-induced iron perturbation is clinically relevant as it relates to therapeutic outcome. METHODS: Iron variables were sequentially assessed in 206 CHC patients undergoing antiviral therapy and were correlated with pretreatment iron status and histology, hemolysis, and therapeutic outcome. RESULTS: At week 1 of therapy, serum iron (SI), transferrin saturation (TS), and serum ferritin (SF) increased markedly in all patients. All iron parameters correlated with hemolysis up to week 4; this correlation was lost for SF at later time points. SF rise during treatment was inversely related to baseline SF and iron deposits in hepatic mesenchymal/Kupffer cells. Both baseline SF and mesenchymal iron significantly correlated with fibrosis at multivariate analysis (P=0.015 and 0.008, respectively). Interestingly, baseline SF, despite good specificity (89%), had low sensitivity in predicting siderosis (25%). During therapy, SI, TS, and hemolysis parameters did not correlate with sustained virological response (SVR), whereas SF rise became an independent predictor of therapeutic response: a 2.5-fold increase of SF at week 12 associated with higher likelihood of SVR (odds ratio 1.91, P=0.032). Accordingly, lack of mesenchymal iron deposits at the baseline biopsy correlated with SVR (odds ratio 3.02, P=0.043). CONCLUSIONS: In CHC, SF is a useful marker for assessing disease duration and progression before starting treatment and for predicting therapeutic response while on therapy. SF rise during antiviral therapy is largely independent of hemolysis and likely indicates activation of macrophages in response to antivirals.

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