Iron Cytotoxicity in Chronic Hepatitis C

Abstract

Iron-induced cytotoxicity in chronic hepatitis C was described in detail based on effectual iron reduction therapy. Without treatment, chronic hepatitis C may progress to cirrhosis and develop hepatocellular carcinoma. The first choice treatment for the disease is interferon. However, the cost-benefit of interferon treatments is so poor that options other than interferon are needed for poor responders. A minimum requirement for managing these patients is good control of disease activity shown by maintaining a low serum level of alanine aminotransferase activity. An index accepted widely is 80 IU/l or less of the enzyme activity. When patients were treated with repeated phlebotomy to remove body iron stores, the mean serum levels of enzyme activities changed from 128 to 63 IU/l. Maintaining patients at an iron deficient state for 5 years or more did not change the staging of liver histology, in contrast with the advanced liver histology in the control patients. Iron generates hydroxyl radicals that mediate peroxidation of membrane lipids. After the proposal of our empirical treatment based on the ultrastructural study of hepatic iron stores, evidence has been accumulated that oxidative stress via lipid peroxides plays an important role in the pathogenesis of chronic hepatitis C. The treatment is not yet authorized in Japan, but is approved in the United States as the first of the options to interferon. Considering the therapeutic effects of iron removal on both biochemical and histological parameters, the safety-proved economical procedure might be recommended for patients as an option to interferon.