Patients with chronic hepatitis C achieving a sustained virological response to peginterferon and ribavirin therapy recover from impaired hepcidin secretion☆

Background/Aims

The aim of this study is to determine the clinical relevance of hepatic producing iron regulatory hormone-hepcidin, on iron overload in patients with chronic hepatitis C (CHC).

Methods

Serum hepcidin was measured in 73 CHC patients by surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS), and compared to those of healthy controls and anemia of inflammation patients, and analyzed their relationship to hepatic hepcidin mRNA expression levels and clinical, hematological, and histological findings. The sequential changes of hepcidin were investigated in 27 CHC patients treated with a 48 week-course of pegylated-interferon (PEG-IFN) plus ribavirin therapy.

Results

Serum hepcidin was positively correlated with hepatic hepcidin mRNA levels, serum ferritin and the degree of hepatic iron deposition in CHC. Serum hepcidin-to-ferritin ratios were significantly lower in HCV positive patients than in HCV negative controls in both hyper- and normal-ferritinemic conditions. This relative impairment of hepcidin production was fully reversible after successful HCV eradication by PEG-IFN plus ribavirin, concomitantly with the improvement of the iron overload condition.

Conclusions

The impairment of hepatic hepcidin production occurring with chronic HCV infection may enhance iron toxicity and lead to disease progression, and modulation or supplementation of hepcidin may be beneficial for these conditions in CHC.

Keywords: Chronic hepatitis C, Iron, Iron-regulated genes, Interferon, Ribavirin, Surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS), Real-time PCR

Abbreviations: CHC, chronic hepatitis C, SELDI-TOF-MS, surface-enhanced laser desorption/ionization time of flight mass spectrometry, PEG, pegylated, IFN, interferon, HCV, hepatitis C virus, AI, anemia of inflammation, SD, standard deviation, CHCA, α-cyano-4-hydroxy-cinnamic acid, AU, arbitrary units, PCR, polymerase chain reaction, TIS, total iron score, SVR, sustained virological responders, IL, interleukin, LPS, lipopolysaccharide