Iron reduction and sustained response to interferon-α therapy in patients with chronic hepatitis C:: Results of an Italian Multicenter Randomized study

OBJECTIVES: 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 greater than or equal to700 mug/g dry wt (men and greater than or equal to500 mug/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 mother 8 months. RESULTS: Virological sustained response was observed in 25 patients (22%), nine (15.8%, 95%, Cl = 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-glutamyl transferase, 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 less than or equal to 1100 mug/g dry wt had a trend toward a higher rate of virological sustained response (p = 0.059) when submitted to treatment B. CONCLUSION: 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.