The team evaluated whether iron reduction by phlebotomy, before interferon-alpha therapy, improves virological sustained response in previously untreated, non-cirrhotic patients with chronic hepatitis C.
The findings of the research were published in the May issue of the American Journal of Gastroenterology.
A total of 114 hepatitis C virus (HCV) RNA-positive patients with hepatic iron concentrations of ≥ 700 µg/g dry wt (men) and ≥ 500 µg/g dry wt (women) were included in the study.
They were stratified according to HCV genotype and gamma-glutamyltransferase values.
The patients were then randomly allocated to interferon alone (6 MU, 3 times a week, Group A) or to phlebotomy until iron depletion followed by interferon (6 MU, 3 times a week, Group B).
After 4 months, the dosage was reduced to 3 MU, 3 times a week, for another 8 months.
Virological sustained response was observed in 25 patients (22%) - 9 (16%) of Group A and 16 (28%) of Group B.
At univariate analysis, the variables found to be associated with the response were HCV genotypes 2-3 and normal gamma-glutamyltransferase.
Higher levels of baseline ALT, normal ALT values, and negativity for HCV-RNA at the 3rd month of therapy were also linked with response.
At multivariate analysis, HCV genotype and ALT levels at enrollment maintained their association with the response.
| Iron reduction improved response to interferon therapy by over 2-fold.
| American Journal of Gastroenterology |
The authors discovered that a trend toward a better response to interferon was observed in patients who received phlebotomy (odds ratio = 2.32).
Furthermore, patients with hepatic iron concentration of ≤ 1100 µg/g dry wt had a trend toward a higher rate of virological sustained response when submitted to treatment B.
Silvia Fargion, of the University of Milan, concluded on behalf of fellow authors, "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."
In an accompanying Editorial, Steven I. Shedlofsky, of the University of Kentucky, Lexington, Kentucky, USA, comments, "The role for routine iron reduction in the therapy of hepatitis C patients remains controversial and is not advocated or mentioned in current reviews of HCV therapy.
"This may be because modern evidence-based medicine requires stronger proof of efficacy than what is currently published, and cannot recommend based on the purely theoretical benefits of iron reduction."
"However, there may also be a bias against using therapies for hepatitis C that are not directed at eradication of virus," he adds.
Nonetheless, in the absence of "official" recommendations, Dr Shedlofsky advocates phlebotomy in all non-acutely ill HCV patients with serum ferritins of < 200 ng/ml.
He concludes that, "Iron reduction using phlebotomy as non-eradicative therapy is safe and relatively inexpensive. It offers potential benefit even if the patient is not a candidate for, cannot tolerate, or failed interferon-ribavirin therapy."