Lack of progressive hepatic fibrosis during long-term therapy with Deferiprone in subjects with transfusion-dependent beta-thalassaemia

Authors
Ian R. Wanless, George Sweeney, Amar P. Dhillon, Maria Guido, Antonio Piga, Renzo Galanello, M. Rita Gamberini, Elias Schwartz, and Alan R. Cohen.

Journal
Blood, 1 September, 2002 – Volume 100, Number 5: 1566-1569

Background
Subjects with thalassaemia often develop liver fibrosis. This complication is known to depend particularly on the presence of viral hepatitis but also on hepatic iron concentration, the distribution of iron within the liver, and age. Thus, while iron chelation therapy with deferoxamine can prevent or improve liver fibrosis in some patients, fibrosis may still occur because of inadequate chelation or chronic hepatitis C.

This study was conducted to determine what role, if any, deferiprone plays in the development of hepatic fibrosis.

Methods

• 56 patients, treated with deferiprone for a mean of 3.1 years at 25 mg/kg/day 3 times daily and no exposure to other chelators, underwent liver biopsy.
• Compliance with therapy was in excess of 95%.
• 45 patients were anti-HCV+ at the time of final biopsies and 11 were seronegative at entry and the end of the study. All were HIV negative.
• The 3 pathologists met to discuss their grading system prior to scoring the samples. Two scoring systems were used for ease of comparison to published work, the Ishak system and the Laennec system.
• 3 pathologists conducted a blinded review of the biopsies.
• 2 biopsies from each patient were received at McMaster University. Each biopsy was assigned a random code and the study coordinator held the randomization code until the pathologists had completed their assessment.

Results – Final biopsies showed no significant differences from the entry biopsies, whether HCV- or HCV+.

The entry biopsies showed an absence or mild fibrosis in the majority of patients and were more severe in the HCV+ patients. The final biopsies showed no significant differences in fibrosis whether HCV- or HCV+. The Wilcoxon rank sum test also showed no significant change in score with time.

Results - Among the final biopsies only 1 HCV+ patient had cirrhosis.

Histological cirrhosis as determined by two of the pathologists was identified in 1 HCV+ patient. That patient had moderate fibrosis scores on the entry biopsy. No other patient in the study developed cirrhosis of the liver.

Conclusions
This study was the largest study to evaluate liver biopsy samples over time in deferiprone-treated patients and revealed no progression of fibrosis attributed to deferiprone use, in agreement with the other smaller studies reported in the literature.

• If you would like to read the entire Wanless study (external site), click here.

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