Liver fibrosis is reduced in patients with iron overload β-thalassemia and hepatitis C given the iron chelator deferasirox, according to Yves Deugnier et al. in the October issue of Gastroenterology.
The liver is the main site of iron accumulation in patients with iron-overload disorders. Storage of excess iron in the liver can lead to tissue damage, collagen formation, and portal fibrosis, eventually resulting in cirrhosis and organ damage. Excess iron also promotes liver fibrogenesis in patients with hepatitis C. Iron chelating drugs increase biliary excretion of iron and protect the liver, heart, and other organs, yet only a few, small studies have evaluated their effects on liver fibrosis in patients with hepatitis C.
Deugnier et al. analyzed liver biopsy samples and other data from 219 patients with β-thalassemia (14% with hepatitis C), collected at baseline and after at least 3 years of treatment with deferasirox. They assessed iron concentrations, fibrosis, necroinflammation, markers of iron overload, and levels of liver enzymes.
The authors found that treatment with deferasirox for at least 3 years stabilized or even reduced liver fibrosis and necroinflammation, as well as reduced levels of alanine aminotransferase (an indicator of liver damage) in iron-overloaded patients.
The stabilization or improvement in fibrosis scores occurred in 46.7% and 30.0% of HCV-positive patients and in 57.2% and 27.2% of HCV-negative patients, respectively.
The surprising finding was that the decrease in liver fibrosis was not associated with reductions in concentrations of iron. Of the 36% of patients who did not have reduced levels of iron after deferasirox therapy, 30% still reduced their level of liver fibrosis by 2 Ishak stages—a higher percentage than that of patients who did have reduced levels of iron after therapy (see figure).
In addition to binding iron, Deugnier et al. propose deferasirox, or its metabolites, might interact with other factors that modulate fibrosis. Studies have reported that deferasirox inhibits the transcription factor NF-κB, which regulates fibrosis in the lung.
In an accompanying editorial, Paul Adams asks whether chelation therapies might become anti-fibrotic therapies for other liver diseases—even those not associated with iron overload. He says further studies are needed to investigate the effects of deferasirox beyond iron removal that could be used to reverse fibrosis.
More Information on Iron Overload:
Read the article online.
Deugnier Y, Turlin B, Ropert M, et al. Improvement in liver pathology of patients with β-thalassemia treated with deferasirox for at least 3 years. Gastroenterology 2011;141:1201–1211.e3
Read the accompanying editorial.
Adams PC. Chelation therapy for secondary iron overload: is the primary effect less iron or less liver fibrosis? Gastroenterology 2011;141:1142–1143.