Reduced serum hepcidin levels in patients with chronic hepatitis C☆

Background/Aims: Patients with chronic hepatitis C (CHC) often have increased liver iron, a condition associated with reduced sustained response to antiviral therapy, more rapid progression to cirrhosis, and development of hepatocellular carcinoma. The hepatic hormone hepcidin is the major regulator of iron metabolism and inhibits iron absorption and recycling from erythrophagocytosis. Hepcidin decrease is a possible pathophysiological mechanism of iron overload in CHC, but studies in humans have been hampered so far by the lack of reliable quantitative assays for the 25-amino acid bioactive peptide in serum (s-hepcidin).

Methods: Using a recently validated immunoassay, we measured s-hepcidin levels in 81 untreated CHC patients and 57 controls with rigorous definition of normal iron status. All CHC patients underwent liver biopsy with histological iron score.

Results: s-hepcidin was significantly lower in CHC patients than in controls (geometric means with 95% confidence intervals: 33.7, 21.5–52.9 versus 90.9, 76.1–108.4ng/mL, respectively; p<0.001). In CHC patients, s-hepcidin significantly correlated with serum ferritin and histological total iron score, but not with s-interleukin-6. After stratification for ferritin quartiles, s-hepcidin increased significantly across quartiles in both controls and CHC patients (chi for trend, p<0.001). However, in CHC patients, s-hepcidin was significantly lower than in controls for each corresponding quartile (analysis of variance, p<0.001).

Conclusions: These results, together with very recent studies in animal and cellular models, indicate that although hepcidin regulation by iron stores is maintained in CHC, the suppression of this hormone by hepatitis C virus is likely an important factor in liver iron accumulation in this condition.

Abbreviations: CHC, chronic hepatitis C, HCV, hepatitis C virus, ANOVA, analysis of variance, CV, coefficient of variation, CIs, confidence intervals, CRP, C-reactive protein, ELISA, enzyme-linked immunosorbent assay, ESR, erythrocyte sedimentation rate, HFE, haemochromatosis type 1 gene, HBV, hepatitis B virus, HCC, hepatocellular carcinoma, mRNA, messenger RNA, ROS, reactive oxygen species, SELDI-TOF MS, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry assay, TIS, total iron score, TS, transferrin saturation

Keywords: Chronic hepatitis C, Hemochromatosis, Hepcidin, Iron overload, Ferritin