LIVER IRON INFLUENCES THE RESPONSE TO INTERFERON-ALPHA THERAPY IN CHRONIC HEPATITIS-C

Objective: To define whether there is any relation between the iron st atus of patients with hepatitis C virus (HCV) chronic liver disease an d their response to interferon therapy. Design: To evaluate the long-t erm response to 1 year of interferon therapy with addition of phleboto mies after 3 months of treatment if at that time alanine aminotransfer ase (ALT) had not normalized in a group of patients with HCV-positive chronic liver disease whose iron status had been characterized. Settin g: A northern Italian hospital. Participants: Fifty-eight anti-HCV-pos itive patients (four HCV-RNA negative) with biopsy proven chronic hepa titis and no evidence of iron overload as indicated by normal transfer rin saturation at the time of enrolment in the study. Intervention: Th ree times a week intramuscular injection of alpha interferon 3 MU for 1 year with addition of phlebotomies (350 ml/week) till iron depletion if after 3 months of interferon therapy ALT had not-normalized. Resul ts: A long-term response was observed in 19 of the 52 patients who com pleted the treatment, four HCV-RNA negative and 15 positive. The four RNA-negative and seven of the 15 RNA-positive long-term responders had been treated with interferon alone, and the other eight also with phl ebotomies. At univariate analysis only HCV genotype, gamma-glutamyltra nspeptidase and liver iron concentration were significantly associated with response whereas sinusoidal iron deposition was of borderline si gnificance. No association was found with sex, age, duration of diseas e, histology, Knodell score, transferrin saturation %, serum ferritin, hepatocytic iron score, and portal iron score. HCV-RNA serum levels, measured in 29 patients, did not correlate with response. At multivari ate analysis liver iron concentration was still significant and one un it reduction of liver iron concentration (natural logarithm transforme d) was associated with 2.95 odds ratio of response. Conclusion: These results indicate that iron in the liver is more closely related to res ponse to interferon than the other variables considered, including HCV characteristics.