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.


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, hyaluronic 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.
Alexander
Jacob
J
Department of Medicine, Division of Gastroenterology, University of Washington Medical Center, Seattle, WA, USA.
Tung
Bruce Y
BY
Croghan
Anne
A
Kowdley
Kris V
KV
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D024061:Collagen Type III / Q000097:blood; D005260:Female; D005293:Ferritins / Q000097:blood; D005355:Fibrosis; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006801:Humans; D000090463:Iron Deficiencies; D008099:Liver / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000097:blood; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D014168:Transferrin / Q000378:metabolism
D015415:Biomarkers; D024061:Collagen Type III; D010446:Peptide Fragments; D012367:RNA, Viral; D014168:Transferrin; D005293:Ferritins; D000410:Alanine Transaminase