Hepcidin mRNA level as a parameter of disease progression in chronic hepatitis C and hepatocellular carcinoma

Hepcidin, a key regulator of iron metabolism, is synthesized by the liver. Hepcidin binds to the iron exporter ferroportin to regulate the release of iron into plasma from macrophages, hepatocytes, and enterocytes.

To study hepcidin expression in liver tissue of patients with hepatocellular carcinoma (HCC), chronic hepatitis C (CHC) and normal human liver biopsies and to compare its level with serum and liver iron indices.

Liver biopsies from 66 patients (36 HCC and 30 CHC) were analysed as well as normal human liver biopsies obtained from 20 healthy liver transplant donors as a control group. Liver function tests, AFP, hepatitis markers, HCV-RNA levels, hemoglobin concentration and serum iron parameters were analyzed. Hepcidin mRNA was quantified in all liver biopsies of patients and controls by real-time PCR. Liver iron concentration (LIC) was evaluated and hepatic iron index (HII) was calculated by dividing LIC in mmol/gm dry weight by the patient's age.

The mean level for hepcidin mRNA in HCC, CHC and healthy controls were 2351±505, 5735±2403 and 16308±2194 copies/ml, respectively; with significant decrease in cancerous (HCC) than non-cancerous (CHC) and control liver tissues. The level was significantly lower in patients with multiple tumour masses. Hepcidin mRNA had a significant positive correlation with synthetic function of the liver (serum albumin and prothrombin concentration) and haemoglobin. In contrast, hepcidin mRNA was negatively correlated with parameters of iron stores as (serum ferritin and HII) and grade of liver fibrosis in both patient groups.

The expression of hepcidin mRNA is decreased in liver tissues of CHC patients and more suppressed in the liver tissues of patients with HCC, suggesting that hepcidin expression appears to be appropriately responsive to iron status and disease progression in cirrhosis and hepatocarcinogenesis.

HCC - Hepcidin - mRNA - Real-time PCR.