Effect of iron depletion on serum markers of fibrogenesis, oxidative stress and serum liver enzymes in chronic hepatitis C: results of a pilot study

Background: Hepatic iron deposition has been associated with decreased response to interferon-alpha monotherapy, and has been speculated to contribute to disease progression in chronic hepatitis C (CHC). We performed this study to evaluate the effect of iron depletion on biochemical and virologic markers, and markers of lipid peroxidation and fibrogenesis. Materials and Methods: Eighteen patients with CHC who did not have a virologic response to interferon monotherapy underwent weekly phlebotomies until iron depletion (serum ferritin < 50 ng/ml). Serum levels of alanine transaminase (ALT), hepatitis C virus-RNA, transferrin saturation, ferritin, 8-isoprostane, hylauronic acid, amino-terminal procollagen III peptide and YKL-40 were measured before and after iron depletion. Results: There was a statistically significant reduction of serum ALT, transferrin saturation and serum ferritin after iron depletion (range 4-11 phlebotomies). Serum ALT returned to normal after iron depletion in four (22%) patients. There was a significant reduction in serum procollagen III peptide level among patients who achieved biochemical response. No significant reduction was noted in serum levels of other markers. Conclusions: Iron depletion was associated with a biochemical response in 22% of patients who did not respond to interferon monotherapy. There was a significant reduction in a key marker of fibrogenesis among patients with biochemical response. These data support longer-term studies of iron depletion in CHC.