Serum ferritin as a predictor of treatment outcome in patients with chronic hepatitis C.
OBJECTIVE
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.
Ferrara
Francesca
F
Department of Internal Medicine, Center for Hemochromatosis, University Hospital of Modena, Italy.
Ventura
Paolo
P
Vegetti
Alberto
A
Guido
Maria
M
Abbati
Gianluca
G
Corradini
Elena
E
Fattovich
Giovanna
G
Ferrari
Carlo
C
Tagliazucchi
Mara
M
Carbonieri
Anna
A
Orlandini
Alessandra
A
Fagiuoli
Stefano
S
Boninsegna
Sara
S
Minola
Eliseo
E
Rizzo
Giovanna
G
Belussi
Fabio
F
Felder
Martina
M
Massari
Marco
M
Pozzato
Gabriele
G
Bonetto
Stefania
S
Rovere
Pierangelo
P
Sardini
Carla
C
Borghi
Athos
A
Zeneroli
Maria Luisa
ML
Toniutto
Pierluigi
P
Rossi
Elisabetta
E
Pietrangelo
Antonello
A
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005293:Ferritins / Q000097:blood*; D006461:Hemolysis / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007501:Iron / Q000097:blood; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D014168:Transferrin / Q000032:analysis; D016896:Treatment Outcome
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014168:Transferrin; D011092:Polyethylene Glycols; D012254:Ribavirin; D005293:Ferritins; D007501:Iron; C100416:peginterferon alfa-2a