title: Iron reduction and sustained response to interferon-alpha therapy in patients with chronic hepatitis C: results of an Italian multicenter randomized study.
abstract: 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.
authors.affiliation: Dipartimento Medicina Interna, Ospedale Maggiore IRCCS, Università di Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fargion
authors.forename: Anna Ludovica
authors.initials: AL
authors.lastname: Fracanzani
authors.forename: Angelo
authors.initials: A
authors.lastname: Rossini
authors.forename: Mauro
authors.initials: M
authors.lastname: Borzio
authors.forename: Oliviero
authors.initials: O
authors.lastname: Riggio
authors.forename: Giovanni
authors.initials: G
authors.lastname: Belloni
authors.forename: Franco
authors.initials: F
authors.lastname: Bissoli
authors.forename: Roberto
authors.initials: R
authors.lastname: Ceriani
authors.forename: Marco
authors.initials: M
authors.lastname: Ballarè
authors.forename: Marco
authors.initials: M
authors.lastname: Massari
authors.forename: Caterina
authors.initials: C
authors.lastname: Trischitta
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Fiore
authors.forename: Anna
authors.initials: A
authors.lastname: Orlandi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Morini
authors.forename: Michela
authors.initials: M
authors.lastname: Mattioli
authors.forename: Silvia
authors.initials: S
authors.lastname: Oldani
authors.forename: Bruno
authors.initials: B
authors.lastname: Cesana
authors.forename: Gemino
authors.initials: G
authors.lastname: Fiorelli
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007501:Iron; D000410:Alanine Transaminase