Iron reduction and sustained response to interferon-alpha therapy in patients with chronic hepatitis C: results of an Italian multicenter randomized study.
OBJECTIVE
It has been suggested that iron depletion improves the response to interferon in patients with chronic hepatitis C. We aimed to evaluate whether iron reduction by phlebotomy before interferon improves the rate of virological sustained response in previously untreated noncirrhotic patients.


METHODS
One hundred fourteen hepatitis C virus (HCV) RNA positive patients with hepatic iron concentrations of > or =700 microg/g dry wt (men) and > or =500 microg/g dry wt (women), stratified according to HCV genotype and gamma-glutamyltransferase values, were randomly allocated to interferon alone (6 MU three times a week) (group A) or to phlebotomy until iron depletion followed by interferon (6 MU three times a week) (group B). After 4 months dosage was reduced to 3 MU three times a week for another 8 months.


RESULTS
Virological sustained response was observed in 25 patients (22%), nine (15.8%, 95% CI = 7.5-27.9) of group A and 16 (28.1%, 95% CI = 17.0-41.6) of group B. At univariate analysis the variables associated with the response were HCV genotypes 2-3, normal gamma-glutamyltransferase, higher levels of baseline ALT, normal ALT values, and negativity for HCV-RNA at the 3rd month of therapy. At multivariate analysis, genotype and ALT levels at enrollment maintained their association with the response. A trend toward a better response to interferon was observed in patients who received phlebotomy (odds ratio = 2.32, 95% CI = 0.96-6.24, p = 0.082). Patients with hepatic iron concentration of < or = 1100 microg/g dry wt had a trend toward a higher rate of virological sustained response (p = 0.059) when submitted to treatment B.


CONCLUSIONS
Iron removal by phlebotomy is able to improve the rate of response to interferon, especially in patients with lower hepatic iron deposits; it could be useful as adjuvant therapy to new therapeutic modalities.
Fargion
Silvia
S
Dipartimento Medicina Interna, Ospedale Maggiore IRCCS, Università di Milano, Italy.
Fracanzani
Anna Ludovica
AL
Rossini
Angelo
A
Borzio
Mauro
M
Riggio
Oliviero
O
Belloni
Giovanni
G
Bissoli
Franco
F
Ceriani
Roberto
R
Ballarè
Marco
M
Massari
Marco
M
Trischitta
Caterina
C
Fiore
Pierluigi
P
Orlandi
Anna
A
Morini
Lorenzo
L
Mattioli
Michela
M
Oldani
Silvia
S
Cesana
Bruno
B
Fiorelli
Gemino
G
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000628:therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007501:Iron / Q000097:blood* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018962:Phlebotomy; D016896:Treatment Outcome
D000998:Antiviral Agents; D016898:Interferon-alpha; D007501:Iron; D000410:Alanine Transaminase