Hepatic iron overload does not prevent a sustained virological response to interferon-alpha therapy: a long term follow-up study in hepatitis C-infected patients with beta thalassemia major.
OBJECTIVE
Transfusion-acquired chronic hepatitis C infection and systemic iron overload are common in patients with beta thalassemia major. The magnitude of hepatic iron overload has been associated with a poor response to interferon-based antiviral therapy for hepatitis C. The aim of this study was to evaluate the effect of hepatic iron concentration (HIC) on response to interferon monotherapy in patients with massive hepatic iron overload.


METHODS
Twenty-eight patients with beta thalassemia major, transfusion-acquired iron overload, and chronic hepatitis C infection were prospectively treated with interferon for 6 months. HIC was measured by atomic absorption spectroscopy before treatment. Serum iron, ferritin, hepatitis C virus genotype, viral load, and liver histology were analyzed.


RESULTS
Eight patients (28%) achieved a sustained virological response that has been durable after a mean of 66 months of follow-up. The median HIC was 2583 microg/g dry weight. There was no difference in HIC between responders and nonresponders to therapy. Serum hepatitis C virus RNA was lower in responders than in nonresponders. Genotype 1 was more frequent in nonresponders, and non-1 genotypes were more frequent in responders, although this did not reach statistical significance because of patient numbers.


CONCLUSIONS
A long term response to interferon is unrelated to HIC in this patient group, and a durable response can occur despite massive iron overload. HIC may be a factor in liver cell injury, but it does not reliably predict a response to interferon therapy.
Sievert
William
W
Monash University Department of Medicine, Monash Medical Centre, Melbourne, Australia.
Pianko
Stephen
S
Warner
Shernyne
S
Bowden
Scott
S
Simpson
Ian
I
Bowden
Don
D
Locarnini
Stephen
S
D000328:Adult; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000187:drug effects* / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D007501:Iron / Q000032:analysis*; D019190:Iron Overload / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D017086:beta-Thalassemia / Q000150:complications* / Q000378:metabolism / Q000473:pathology
D000998:Antiviral Agents; D007371:Interferon-gamma; D007501:Iron