Serum ferritin levels were independently shown to be a risk factor for poor response to treatment in hepatitis C virus (HCV) infection (Hepatology 2012; 55: 1038-47). This article adds additional information to previous work which has shown that increased iron can be a comorbid factor in chronic viral hepatitis and other liver diseases.
This study used the Swiss Hepatitis C Cohort Study (SCCS) (n=3648). In this group, the success of treatment with pegylated interferon alpha and ribavirin were correlated with clinical and histological features.
Ferritin levels ≥ the sex-specific median values was one of the strongest pretreatment predictors of treatment failure (OR 0.45). It had a similar predictive effect as the IL28B genotype. In addition, higher ferritin levels were associated with severe liver fibrosis (OR 2.67) and steatosis (OR 2.29). For women the sex-specific median for ferritin level was 85 μg/L and for men it was 203 μg/L. The authors note that these cutoffs are quite close to the upper limits of normal of the general population (150 and 300 respectively).
Mechanistically, HCV interferes with the host’s iron metabolism leading to iron accumulation in the liver. Part of this is explained by down-regulation of hepcidin (Help with hepcidin). Part is due to ferritin acting as an acute phase reactant to inflammation. Ultimately, excess iron promotes liver inflammation, oxidative stress and mitochondrial dysfunction.
How important ferritin will be with newer therapies is not clear. It is likely that patients that are less responsive to dual therapy (pegylated interferon/ribavirin) will have poorer response as well to triple or quadruple therapies.
Additional references/previous related posts:
- –The cost of progress in treating Hepatitis C
- –Looking for trouble
- –HCV now more deadly than HIV
- –Drink Up!
- –Curing Hepatitis C without interferon
- –Another life-threatening complication of HCV
- -Gastroenterology 2010; 138: 905. Iron overload, but not HFE mutations, associated with more severe NASH
- -Am J Gastroenterol 2002; 97: 1-4. Iron as comorbid factor in chronic viral hepatitis.
- -Gastrotentology 2006; 131: 1440-51. Role of iron/HFE mutations in response to treatment of chronic viral hepatitis.